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Page 1 of 102

Total knee arthroplasty: does ultra-early physical therapy improve functional outcomes and reduce length of stay? A retrospective cohort study

The Enhanced Recovery After Surgery (ERAS) Society recommends that after total knee arthroplasty (TKA), patients should be mobilized early. However, there is no consensus on how early physical therapy should b...

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Preoperative prediction model for risk of readmission after total joint replacement surgery: a random forest approach leveraging NLP and unfairness mitigation for improved patient care and cost-effectiveness

The Center for Medicare and Medicaid Services (CMS) imposes payment penalties for readmissions following total joint replacement surgeries. This study focuses on total hip, knee, and shoulder arthroplasty proc...

Comparison of minimally invasive transforaminal lumbar interbody fusion and midline lumbar interbody fusion in patients with spondylolisthesis

This study aimed to compare surgical outcomes, clinical outcomes, and complications between minimally invasive transforaminal lumbar interbody fusion (MIS TLIF) and midline lumbar interbody fusion (MIDLIF) in ...

Correction: A risk prediction model for postoperative recovery of closed calcaneal fracture: a retrospective study

The original article was published in Journal of Orthopaedic Surgery and Research 2020 15 :100

The varying clinical effectiveness of single, three and five intraarticular injections of platelet-rich plasma in knee osteoarthritis

To investigate the variations in clinical effectiveness among patients diagnosed with knee osteoarthritis who underwent intra-articular administration of platelet-rich plasma using single, triple, or quintuple...

Total knee arthroplasty following lateral closing-wedge high tibial osteotomy versus primary total knee arthroplasty: a propensity score matching study

The disparity in patient-reported outcomes between total knee arthroplasty (TKA) following high tibial osteotomy (HTO) and primary TKA has yet to be fully comprehended. This study aims to compare the patient-r...

Comparison of the forearm rotation restriction capacities of four upper-extremity immobilization methods: there is no difference between single and double sugar tong splinting

The aim of this study was to compare the effects of four different immobilization methods [single sugar tong splint (SSTS), double sugar tong splint (DSTS), short arm cast (SAC), and long arm cast (LAC)] commo...

Evaluating lumbar disc degeneration by MRI quantitative metabolic indicators: the perspective of factor analysis

This study aimed to investigate an early diagnostic method for lumbar disc degeneration (LDD) and improve its diagnostic accuracy.

Effects of various load magnitudes on ACL: an in vitro study using adolescent porcine stifle joints

The escalating incidence of anterior cruciate ligament (ACL) injuries, particularly among adolescents, is a pressing concern. The study of ACL biomechanics in this demographic presents challenges due to the sc...

Demonstrating the effectiveness of intra-articular prolotherapy combined with peri-articular perineural injection in knee osteoarthritis: a randomized controlled trial

This study aimed to compare the efficacy of intra-articular prolotherapy (IG) combined with peri-articular perineural injection (PG) in the management of knee osteoarthritis (KOA).

Precise execution of personalized surgical planning using three-dimensional printed guide template in severe and complex adult spinal deformity patients requiring three-column osteotomy: a retrospective, comparative matched-cohort study

The surgical treatment of severe and complex adult spinal deformity (ASD) commonly required three-column osteotomy (3-CO), which was technically demanding with high risk of neurological deficit. Personalized t...

Factors influencing the posterior cruciate ligament buckling phenomenon—a multiple linear regression analysis of bony and soft tissue structures of the knee joint

To determine whether posterior cruciate ligament (PCL) buckling (angular change) is associated with anterior cruciate ligament (ACL) status (intact or ruptured), meniscal bone angle (MBA), anterior tibial tran...

Randomised controlled trial of tourniquet associated pain generated in lower limb after exsanguination by Esmarch bandage versus limb elevation

Tourniquets are common adjuncts in the operating theatre but can be associated with post-operative pain. This study was designed to compare what effect pre-tourniquet Esmarch bandage exsanguination has on pain...

Correction: Impact of preoperative anemia on patients undergoing total joint replacement of lower extremity: a systematic review and meta-analysis

Effectiveness and safety of polyacrylamide hydrogel injection for knee osteoarthritis: results from a 12-month follow up of an open-label study.

There are few effective osteoarthritis (OA) therapies. A novel injectable polyacrylamide hydrogel (iPAAG) previously demonstrated efficacy and safety up to week 26 in an open-label study of knee OA. Here we re...

Three-dimensional printed custom-made modular talus prosthesis in patients with talus malignant tumor resection

Talar malignant tumor is extremely rare. Currently, there are several alternative management options for talus malignant tumor including below-knee amputation, tibio-calcaneal arthrodesis, and homogenous bone ...

Comparative effectiveness of low-level laser therapy versus muscle energy technique among diabetic patients with frozen shoulder: a study protocol for a parallel group randomised controlled trial

Diabetes mellitus is one of the fastest-growing health challenges of the twenty-first century with multifactorial impact including high rates of morbidity and mortality as well as increased healthcare costs. I...

Intelligent robot-assisted fracture reduction system for the treatment of unstable pelvic fractures

Precise and minimally invasive closed reduction is the premise of minimally invasive internal fixation. This paper aims to explore the safety and efficacy of a robot-assisted fracture reduction system (RAFR) i...

Preoperative handgrip strength can predict early postoperative shoulder function in patients undergoing arthroscopic rotator cuff repair

Rotator cuff tears (RCTs) are a common musculoskeletal disorder, and arthroscopic rotator cuff repair (ARCR) is widely performed for tendon repair. Handgrip strength correlates with rotator cuff function; howe...

Efficacy of PE-PLIF with a novel ULBD approach for lumbar degeneration diseases: a large-channel endoscopic retrospective study

This study aims to assess the effectiveness of Percutaneous Endoscopic Posterior Lumbar Interbody Fusion (PE-PLIF) combined with a novel Unilateral Laminotomy for Bilateral Decompression (ULBD) approach using ...

Critical distance of the sacroiliac joint for open reduction using screw fixation for traumatic sacroiliac joint diastasis: a retrospective study

Osteosynthesis for sacroiliac joint (SIJ) diastasis using an iliosacral screw (ISS) and a trans-iliac-trans-sacral screw (TITSS) can be performed using a closed or an open method. However, no clear indication ...

Combined with the first dorsal (plantar) metatarsal artery pedicle free bilobed flap with a cell scaffold for the repair of a mid-distal adjacent finger defect: a retrospective study

Assessing the clinical effectiveness of combining with the first dorsal (plantar) metatarsal artery pedicle free bilobed flap with a cell scaffold to repair mid-distal defects in adjacent fingers.

Different radius of curvature at the talus trochlea from northern Chinese population measured using 3D model

To analyze the curvature characteristics of the talus trochlea in people from northern China in different sex and age groups.

Research progress in the pathogenesis of hormone-induced femoral head necrosis based on microvessels: a systematic review

Hormonal necrosis of the femoral head is caused by long-term use of glucocorticoids and other causes of abnormal bone metabolism, lipid metabolism imbalance and blood microcirculation disorders in the femoral ...

Investigating the impact of cartilaginous endplate herniation on recovery from percutaneous endoscopic lumbar discectomy

This study aimed to evaluate the influence of herniation of cartilaginous endplates on postoperative pain and functional recovery in patients undergoing percutaneous endoscopic lumbar discectomy (PELD) for lum...

Outcomes of surgical treatment of patellar instability in children with Down syndrome

patellar instability is a relatively frequent musculoskeletal disorder in children with Down syndrome (DS). However, such a condition has seldom been studied in the literature, even less its surgical treatment...

Positive buttress reduction in femoral neck fractures: a literature review

Femoral neck fractures (FNFs) in young adults are usually caused by high-energy trauma, and their treatment remains a challenging issue for orthopedic surgeons. The quality of reduction is considered an import...

Clinical effect of full endoscopic lumbar annulus fibrosus suture

The aim of this study was to investigate the clinical efficacy of full endoscopic lumbar annulus fibrosus suture in the treatment of single-segment lumbar disc herniation (LDH).

Upregulation of circ_0076684 in osteosarcoma facilitates malignant processes by mediating miRNAs/CUX1

Circular RNAs (circRNAs) are a newly appreciated type of endogenous noncoding RNAs that play vital roles in the development of various human cancers, including osteosarcoma (OS). In this study, we investigated...

A Novel growth guidance system for early onset scoliosis: a preliminary in vitro study

The purpose of the study was to describe a novel growth guidance system, which can avoid metal debris and reduce the sliding friction forces, and test the durability and glidability of the system by in vitro t...

Biomechanical and clinical outcomes of 3D-printed versus modular hemipelvic prostheses for limb-salvage reconstruction following periacetabular tumor resection: a mid-term retrospective cohort study

Debates persist over optimal pelvic girdle reconstruction after acetabular tumor resection, with surgeons grappling between modular and 3D-printed hemipelvic endoprostheses. We hypothesize superior outcomes wi...

CircPRKD3/miR-6783-3p responds to mechanical force to facilitate the osteogenesis of stretched periodontal ligament stem cells

The mechanotransduction mechanisms by which cells regulate tissue remodeling are not fully deciphered. Circular RNAs (circRNAs) are crucial to various physiological processes, including cell cycle, differentia...

Cross-cultural adaptation, reliability, validity and responsiveness of the Michigan Hand Outcomes Questionnaire (MHQ-Sp) in Spain

The Michigan Hand Outcomes Questionnaire (MHQ) is a self-report tool widely recognized for measuring the health status of patients with hand and wrist problems from a multidimensional perspective . The aim of this...

The extracts of osteoblast developed from adipose-derived stem cell and its role in osteogenesis

Cell-based therapy has become an achievable choice in regenerative medicines, particularly for musculoskeletal disorders. Adipose-derived stem cells (ASCs) are an outstanding resource because of their ability ...

One-hole split endoscope versus unilateral biportal endoscopy for lumbar spinal stenosis: a retrospective propensity score study

The one-hole split endoscopy (OSE) was first proposed and clinically applied in China in 2019. The aim of this study was to compare the clinical efficacy of one-hole split endoscopy (OSE) and unilateral biport...

Robotic-assisted plate fixation of the anterior acetabulum - clinical description of a new technique

We present a detailed procedure for the robotic-assisted plate osteosynthesis of an anterior acetabular fracture. The purpose of this work was to describe a robotic-assisted minimally invasive technique as a p...

Risk factors for poor outcomes in patients with acute lower leg compartment syndrome: a retrospective study of 103 cases

The primary aim of this study was to investigate the risk factors associated with poor outcomes following acute compartment syndrome (ACS) of lower leg. The secondary objective was to determine if delayed fasc...

Relationship between lipid metabolism, coagulation and other blood indices and etiology and staging of non-traumatic femoral head necrosis: a multivariate logistic regression-based analysis

To analyze the relationship between lipid metabolism, coagulation function, and bone metabolism and the contributing factor and staging of non-traumatic femoral head necrosis, and to further investigate the fa...

Relationship between sarcopenia and fatty liver in middle-aged and elderly patients with type 2 diabetes mellitus

In this study, we investigated the relationship between sarcopenia and fatty liver in middle-aged and elderly patients diagnosed with type 2 diabetes mellitus (T2DM) to provide a theoretical foundation for the...

Impact of preoperative anemia on patients undergoing total joint replacement of lower extremity: a systematic review and meta-analysis

Preoperative anemia increases postoperative morbidity, mortality, and the risk of allogeneic transfusion. However, the incidence of preoperative anemia in patients undergoing total hip arthroplasty and total k...

Predictors of success of pharmacological management in patients with chronic lower back pain: systematic review

Conservative management is recommended as the first therapeutic step in chronic low back pain (LBP), but there is no available evidence regarding the possible effect of patients’ baseline characteristics on th...

Evaluation of the consistency of the MRI- based AI segmentation cartilage model using the natural tibial plateau cartilage

The study aims to evaluate the accuracy of an MRI-based artificial intelligence (AI) segmentation cartilage model by comparing it to the natural tibial plateau cartilage.

Robot-assisted anterior cruciate ligament reconstruction based on three-dimensional images

Background  Tunnel placement is a key step in anterior cruciate ligament (ACL) reconstruction. The purpose of this study was to evaluate the accuracy of bone tunnel drilling in arthroscopic ACL reconstruction assi...

Preoperative MRI-based endplate quality: a novel tool for predicting cage subsidence after anterior cervical spine surgery

The objective of this study was to examine the predictive value of a newly developed MRI-based Endplate Bone Quality (EBQ) in relation to the development of cage subsidence following anterior cervical discecto...

KLF5 promotes the ossification process of ligamentum flavum by transcriptionally activating CX43

Ossification of ligamentum flavum (OLF) is a prevalent degenerative spinal disease, typically causing severe neurological dysfunction. Kruppel-like factor 5 (KLF5) plays an essential role in the regulation of ...

Exosomes derived from M2 macrophages prevent steroid-induced osteonecrosis of the femoral head by modulating inflammation, promoting bone formation and inhibiting bone resorption

Inflammatory reactions are involved in the development of steroid-induced osteonecrosis of the femoral head(ONFH). Studies have explored the therapeutic efficacy of inhibiting inflammatory reactions in steroid...

Meta-analysis of the efficacy and safety of OLIF and TLIF in the treatment of degenerative lumbar spondylolisthesis

To systematically evaluate the difference in clinical efficacy between two surgical approaches, oblique lateral approach and intervertebral foraminal approach, in the treatment of degenerative lumbar spondylol...

Circ_0044235 regulates the development of osteoarthritis by the modulation of miR-375/PIK3R3 axis

Circular RNAs (circRNAs) play an important role in osteoarthritis (OA). However, the role of circRNA in OA is still unclear. Here, we explored the role and mechanism of circ_0044235 in OA.

Percutaneous kyphoplasty with or without posterior pedicle screw fixation for the management of severe osteoporotic vertebral compression fractures with nonunion

To assess the radiographic outcomes, clinical outcomes and complications of percutaneous kyphoplasty (PKP) with and without posterior pedicle screw fixation (PPSF) in the treatment of severe osteoporotic verte...

Simplified S1 vertebral bone quality score independently predicts proximal junctional kyphosis after surgery for degenerative lumbar scoliosis

Our study aimed to assess the effectiveness of the simplified S1 vertebral bone quality (VBQ) score in predicting the incidence of proximal junctional kyphosis (PJK) after surgery for degenerative lumbar scoli...

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Journal of Orthopaedic Surgery and Research

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Orthopaedics articles from across Nature Portfolio

Orthopaedics is a medical specialty concerned with the prevention and treatment of disorders of the musculoskeletal system by use of surgical and non-surgical methods.

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Histological and immunohistochemical analyses of articular cartilage during onset and progression of pre- and early-stage osteoarthritis in a rodent model

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Effects of static exercises on hip muscle fatigue and knee wobble assessed by surface electromyography and inertial measurement unit data

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Finite element study on the micromechanics of cement-augmented proximal femoral nail anti-rotation (PFNA) for intertrochanteric fracture treatment

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Official Journal of the Italian Society of Orthopaedics and Traumatology

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Page 1 of 17

Accuracy of cup placement compared with preoperative surgeon targets in primary total hip arthroplasty using standard instrumentation and techniques: a global, multicenter study

Acetabular cup positioning in total hip arthroplasty (THA) is closely related to outcomes. The literature has suggested cup parameters defined by the Lewinnek safe zone; however, the validity of such measures...

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Metal-backed or all-poly tibial components: which are better for medial unicompartmental knee arthroplasty? A propensity-score-matching retrospective study at the 5-year follow-up

This retrospective medium-term follow-up study compares the outcomes of medial fixed-bearing unicompartmental knee arthroplasty (mUKA) using a cemented metal-backed (MB) or an all-polyethylene (AP) tibial comp...

Unravelling variations: an examination of entry point selection in proximal femoral cephalomedullary nailing

The exact positioning of the cephalomedullary (CM) nail entry point for managing femoral fractures remains debatable, with significant implications for fracture reduction and postoperative complications. This ...

Autogenous structural bone graft reconstruction of ≥ 10-mm-deep uncontained medial proximal tibial defects in primary total knee arthroplasty

Management of uncontained medial proximal tibial defects during primary total knee arthroplasty (TKA) can be challenging, especially for defects ≥ 10 mm in depth. This study sought to assess the outcomes of au...

Polytherapy versus monotherapy in the treatment of tibial non-unions: a retrospective study

Treating tibial non-unions efficiently presents a challenge for orthopaedic trauma surgeons. The established gold standard involves implanting autologous bone graft with adequate fixation, but the addition of ...

Lateralising reverse shoulder arthroplasty using bony increased offset (BIO-RSA) or increasing glenoid component diameter: comparison of clinical, radiographic and patient reported outcomes in a matched cohort

This study aims to compare the range of motion (ROM) of reverse shoulder arthroplasty lateralised by bony increased offset (BIO-RSA) using a standard 38-mm (mm) component to regular reverse shoulder arthroplas...

Delaying anterior cruciate ligament reconstruction for more than 3 or 6 months results in lower risk of revision surgery

The objective of this study is to investigate the risk of revision surgery when delaying anterior cruciate ligament reconstruction (ACLR) past 3 months or 6 months after injury.

Functional and oncological outcomes of patients with proximal humerus osteosarcoma managed by limb salvage

Osteosarcoma is the most common primary bone malignancy in skeletally immature patients. The proximal humerus is the third most common site of osteosarcoma. The literature shows a paucity of published data con...

Capacitive biophysical stimulation improves the healing of vertebral fragility fractures: a prospective multicentre randomized controlled trial

Capacitively coupling electric fields (CCEF) is a method of non-invasive biophysical stimulation that enhances fracture repair and spinal fusion. This multicentre randomized controlled trial aimed to further e...

Interlocking intramedullary nail for forearm diaphyseal fractures in adults—A systematic review and meta-analysis of outcomes and complications

The purpose of this systematic review is to examine the outcomes, complications, and potential advantages of using anatomical interlocking intramedullary nails (IMN) in the treatment of radius and ulnar shaft ...

Evaluation of time to reimplantation as a risk factor in two-stage revision with static spacers for periprosthetic knee joint infection

We investigated the time to reimplantation (TTR) during two-stage revision using static spacers with regard to treatment success and function in patients with chronic periprosthetic joint infection (PJI) of th...

TikTok content as a source of health education regarding epicondylitis: a content analysis

This study aimed to assess the validity and informational value of TikTok content about epicondylitis. The hypothesis tested herein was that TikTok video content would not provide adequate and valid information.

Optimizing periprosthetic fracture management and in-hospital outcome: insights from the PIPPAS multicentric study of 1387 cases in Spain

The incidence of all periprosthetic fractures (PPF), which require complex surgical treatment associated with high morbidity and mortality, is predicted to increase. The evolving surgical management has create...

Unexpected early loosening of rectangular straight femoral Zweymüller stems with an alumina-reduced surface after total hip arthroplasty—a prospective, double-blind, randomized controlled trial

Alumina particles from the grit blasting of Ti-alloy stems are suspected to contribute to aseptic loosening. An alumina-reduced stem surface was hypothesized to improve osseointegration and show comparable sho...

Three-dimensional printed models can reduce costs and surgical time for complex proximal humeral fractures: preoperative planning, patient satisfaction, and improved resident skills

Proximal humeral fractures (PHFs) are still controversial with regards to treatment and are difficult to classify. The study’s objective is to show that preoperative planning performed while handling a three-d...

Reverse shoulder arthroplasty with a 155° neck-shaft angle inlay implant design without reattachment of the subscapularis tendon results in satisfactory functional internal rotation and no instability: a cohort study

The aim of this study was to use the Activities of Daily Living which require Internal Rotation (ADLIR) questionnaire to assess the functional internal rotation in patients who had undergone reverse shoulder a...

Direct anterior approach with conventional instruments versus robotic posterolateral approach in elective total hip replacement for primary osteoarthritis: a case–control study

The purpose of this study is to compare peri-operative and short-term outcomes in patients who underwent elective total hip replacement (THA) for primary osteoarthritis (OA) with direct anterior approach (DAA)...

The effect of cellular nuclear function alteration on the pathogenesis of shoulder adhesive capsulitis: an immunohistochemical study on lamin A/C expression

The network of intermediate filament proteins underlying the inner nuclear membrane forms the nuclear lamina. Lamins have been associated with important cellular functions: DNA replication, chromatin organizat...

All-epiphyseal anterior cruciate ligament reconstruction yields superior sports performances than the trans-epiphyseal technique in skeletally immature patients: a systematic review

Anterior cruciate ligament (ACL) tears in skeletally immature patients are increasingly common. Evidence comparing the outcomes of all-epiphyseal versus trans-epiphyseal ACL reconstruction in skeletally immatu...

Risk factors for early septic failure after two-stage exchange total knee arthroplasty for treatment of periprosthetic joint infection

The cause of early septic failure after two-stage exchange revision total knee arthroplasty (TKA) for chronic periprosthetic joint infection (PJI) and the factors affecting it are not well known. The purpose o...

Suprapatellar tibial fracture nailing is associated with lower rate for acute compartment syndrome and the need for fasciotomy compared with the infrapatellar approach

Intramedullary tibial nailing (IMN) is the gold standard for stabilizing tibial shaft fractures. IMN can be performed through an infra- or suprapatellar approach.

Preoperative antibiotic prophylaxis and the incidence of surgical site infections in elective clean soft tissue surgery of the hand and upper limb: a systematic review and meta-analysis

Surgical site infections (SSI) are the most frequent early complications of hand surgeries. However, the indications still remain uncertain for antibiotic prophylaxis in elective clean soft tissue surgeries of...

High satisfaction rate and range of motion can be expected in frozen shoulder after awake manipulation with brachial plexus block

Adhesive capsulitis (AC) is a disease of the glenohumeral joint that is characterized by pain and both passive and active global stiffness with a slow and insidious onset. The disease can occur spontaneously (...

Validation of Roussouly classification in predicting the occurrence of adjacent segment disease after short-level lumbar fusion surgery

Recent studies demonstrated that restoring sagittal alignment to the original Roussouly type can remarkably reduce complication rates after adult spinal deformity surgery. However, there is still no data provi...

Antithrombotic prophylaxis following total hip arthroplasty: a level I Bayesian network meta-analysis

Several clinical investigations have compared different pharmacologic agents for the prophylaxis of venous thromboembolism (VTE). However, no consensus has been reached. The present investigation compared enox...

Transforaminal lumbar interbody fusion with a tantalum cage: lumbar lordosis redistribution and sacral slope restoration with a modified posterior technique

Transforaminal lumbar interbody fusion (TLIF), a commonly used procedure in spine surgery, has the advantage of a lower incidence of nerve lesions compared to the posterior lumbar interbody fusion (PLIF) techn...

Arthrosis diagnosis and treatment recommendations in clinical practice: an exploratory investigation with the generative AI model GPT-4

The spread of artificial intelligence (AI) has led to transformative advancements in diverse sectors, including healthcare. Specifically, generative writing systems have shown potential in various applications...

Greater medial proximal tibial slope is associated with bone marrow lesions in middle-aged women with early knee osteoarthritis

Bone marrow lesion (BML) is an important magnetic resonance finding (MRI) finding that predicts knee osteoarthritis. The purpose of this study was to investigate the influence of proximal tibial morphology on ...

Reverse shoulder arthroplasty in obstetric brachial plexus injury: our experience with shoulder motion analysis

Obstetric brachial plexus injury (OBPI) is a weakening or paralysis of the upper arm caused by brachial plexus injury followed by a muscle paralysis with severe repercussions on the movement of the shoulder jo...

Clinical effects of different center of rotation reconstructions in total hip arthroplasty after femoral neck fractures: a cohort study including a follow-up analysis on patient’s mobility and daily living ability

The aim of this study is a clinical evaluation of the center of rotation (COR) placement towards a patient’s recovery with respect to daily living ability and mobility. In past experiments based on three-dimen...

Standard views do not suffice in assessing distal scaphoid articular cannulated screw penetration

Articular screw penetration is one of the most common hardware-related problems after scaphoid fracture fixation, occurring in up to two-thirds of patients, in particular into the scaphotrapezotrapezoidal (STT...

Complication rates after proximal femoral nailing: does level of training matter?

Surgical treatment of pertrochanteric fractures is one of the most performed surgeries in orthogeriatrics. Proximal femoral nailing, the most performed procedure, is often used as a training surgery for young ...

Bernese periacetabular osteotomy (PAO): from its local inception to its worldwide adoption

The development of the Bernese periacetabular osteotomy (PAO) is based on a structured approach starting with an analysis of the preexisting procedures to improve the coverage of the femoral head and was follo...

Correct positioning of the calcar screw leads to superior results in proximal humerus fractures treated with carbon-fibre-reinforced polyetheretherketone plate osteosynthesis with polyaxial locking screws

Plate osteosynthesis with implants made of carbon-fibre-reinforced polyetheretherketone (CFR-PEEK) has recently been introduced for the treatment of fractures of the proximal humerus (PHFs). The advantages of ...

LARAI portal provides a safe method for lateral meniscus repair: three-dimensional computed tomography and cadaveric assessment

Lateral, All-Round and All-Inside (LARAI) portal is a viewing or working portal for observing and repairing the lesions of the lateral meniscus. However, there are safety concerns about popliteal artery (PA) i...

Functional leg performance 2 years after ACL surgery: a comparison between InternalBrace™-augmented repair versus reconstruction versus healthy controls

While clinical and patient-reported outcomes have been investigated in patients after InternalBrace™-augmented anterior cruciate ligament repair (ACL-IB), less is known regarding restoration of functional perf...

Higher pelvic incidence values are a risk factor for trans-iliac trans-sacral screw malposition in sacroiliac complex fracture treatment

Percutaneous iliosacral (IS) screw fixation and trans-iliac trans-sacral (TITS) screw fixation are clinically effective treatments of posterior pelvic sacroiliac fractures. In order to accurately assess the sa...

Efficacy and safety of modular versus monoblock stems in revision total hip arthroplasty: a systematic review and meta-analysis

Both modular and monoblock tapered fluted titanium (TFT) stems are increasingly being used for revision total hip arthroplasty (rTHA). However, the differences between the two designs in clinical outcomes and ...

National spine surgery registries’ characteristics and aims: globally accepted standards have yet to be met. Results of a scoping review and a complementary survey

Surgery involving implantable devices is widely used to solve several health issues. National registries are essential tools for implantable device surveillance and vigilance. In 2017, the European Union encou...

Anterior debridement combined with autogenous iliac bone graft fusion for the treatment of lower cervical tuberculosis: a multicenter retrospective study

This study aimed to analyze the clinical efficacy of one-stage anterior debridement of lower cervical tuberculosis using iliac crest bone graft fusion and internal fixation.

Italian Orthopaedic and Traumatology Society (SIOT) position statement on the non-surgical management of knee osteoarthritis

Knee osteoarthritis (OA) is a chronic disease associated with a severe impact on quality of life. However, unfortunately, there are no evidence-based guidelines for the non-surgical management of this disease....

Consensus for management of sacral fractures: from the diagnosis to the treatment, with a focus on the role of decompression in sacral fractures

There is no evidence in the current literature about the best treatment option in sacral fracture with or without neurological impairment.

Intramedullary nailing versus cemented plate for treating metastatic pathological fracture of the proximal humerus: a comparison study and literature review

Pathological fracture of the humerus causes severe pain, limited use of the hand, and decreased quality of life. This study aimed to compare the outcomes of intramedullary nailing and locking plate in treating...

Not all questions are created equal: the weight of the Oxford Knee Scores questions in a multicentric validation study

The Oxford Knee Score (OKS) has been designed for patients with knee osteoarthritis and has a widespread use. It has 12 questions, with each question having the same weight for the overall score. Some authors ...

Are the outcomes of single-stage open reduction and Dega osteotomy the same when treating DDH in patients younger than 8 years old? A prospective cohort study

The primary objective was to report our early results after a one-stage procedure [open reduction (OR), Dega pelvic osteotomy (DPO), and femoral osteotomy (FO) when needed] for surgical management of a cohort ...

Carbon-fibre plates for traumatic and (impending) pathological fracture fixation: Where do we stand? A systematic review

Carbon-fibre (CF) plates are increasingly used for fracture fixation. This systematic review evaluated complications associated with CF plate fixation. It also compared outcomes of patients treated with CF pla...

Load-induced increase in muscle activity during 30° abduction in patients with rotator cuff tears and control subjects

Rotator cuff muscles stabilise the glenohumeral joint and contribute to the initial abduction phase with other shoulder muscles. This study aimed to determine if the load-induced increase in shoulder muscle ac...

Combined femoral and tibial component total knee arthroplasty device rotation measurement is reliable and predicts clinical outcome

The optimal total knee arthroplasty (TKA) rotational alignment and how best to obtain and measure it are debatable. The aim was to analyse the reliability of the Berger femoral, three different tibial and four...

New bone formation accelerates during lower limb lengthening and deformity correction in children with Ollier’s disease

Ollier’s disease can cause severe length discrepancy of the lower extremities and deformity in children. Osteotomy and limb lengthening with external fixation can correct the limb deformity. This study evaluat...

Managing early complications in total hip arthroplasty: the safety of immediate revision

Immediate revision refers to a reoperation that involves resetting, draping, and exchanging the implant, after wound closure in total hip arthroplasty. The purpose of this study is to investigate the impact of...

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Official Journal of SIOT  Italian Society of Orthopaedics and Traumatology

Affiliated with Official Journal of AUOT - Accademia Universitaria di Ortopedia e Traumatologia

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Orthopaedic Surgery

Orthopaedic Research and Clinical Trials

The Department of Orthopaedic Surgery’s distinguished history is grounded on Johns Hopkins Medicine’s principle that laboratory research and bedside teaching need to coexist in the instruction and practice of medicine. The creation of a formal Research Division and the Center for Musculoskeletal Research in 2009 provided a nexus for basic and translational research related to the musculoskeletal system.

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Our Team | Clinical Trials | Research Labs

Training and Enrichment Programs T32 Training Program

A NIH-sponsored T32 training program combines the training of orthopaedic residents and postdoctoral scientists through a unique structure, which requires both research and didactic phases to occur concurrently by teams of trainees.

Clinical Trials

For a complete list of available clinical trials, search the database at the  Johns Hopkins Institute for Clinical and Translational Research . You can search by condition, researcher or doctor’s name.

Experimental Procedure for Children With Knee Cartilage Defects

Summary: A study of MACI in patients aged 10 to 17 years with symptomatic chondral or osteochondral defects of the knee (PEAK). 

Objective: To evaluate an experimental treatment for knee cartilage defects called membrane-induced autologous chondrocyte implantation (MACI).

Principle Investigator: R. Jay Lee, M.D.

Eligibility Criteria: Children age 11-17 with knee cartilage defects

Contact: Gabrielle Richard ( [email protected] )

Learn more about this study.

Integra® Titan™ Modular Shoulder System Generation 2.5 for Primary Shoulder Joint Replacement

Summary: A Post-Market, Prospective, Multi-Center, Open-Label, Single Arm Clinical Evaluation of the Integra TitanTM Modular Shoulder System 2.5 for Primary Shoulder Joint Replacement (IRB00169712).

Objective: To evaluate 2-year implant survivorship in subjects who receive the TSS-2.5 when used for primary shoulder arthroplasty.

Principle Investigator: Umasuthan Srikumaran, M.D., M.P.H., M.B.A.

Eligibility Criteria: Candidate for total shoulder arthroplasty.

Contact: Sanjana Vattigunta ( 443-516-1550  or  [email protected] )

Post-operative Pain Control Following Shoulder Surgery

Summary: A study of MACI in patients aged 10 to 17 years with symptomatic chondral or osteochondral defects of the knee (PEAK). 

Objective: Evaluate overall pain medication consumption following surgical treatment for shoulder pathology

Eligibility Criteria: Opioid-naive adults age 18-90 years old planning to undergo surgical treatment for shoulder pathology with Dr. Uma Srikumaran.

Optimize Low Back Pain

Objective: Improve health care for patients with chronic lower back pain (LBP) and increase the likelihood that patients obtain outcomes that matter most to them.

Principle Investigator: Richard Skolasky, Sc.D.

Eligibility Criteria: Adults age 18 - 64 years old, meets NIH Task Force definition of chronic LBP, had a healthcare visit for LBP in the past 90 days and have moderate levels of pain and disability.

Contact: Tricia Kirkhart ( 410-502-4453  or  [email protected] )

Dysport® (abobotulinumtoxinA) as an Adjunctive Treatment to Bracing in the Management of Adolescent Idiopathic Scoliosis (AIS)

Objective: To evaluate the combined effect of botulinum toxin A (administered as Dysport®) and bracing in children with adolescent idiopathic scoliosis.

Principle Investigator: Paul D. Sponseller, M.D.

Eligibility Criteria: Diagnosed with AIS, 10 to 16-year-old children.

Contact: Vivian Tran and Varun Puvanesarajah ( 410-955-3136  or  [email protected] )

Participants in this study will be compensated.

Featured Research Stories

Study finds delayed acl surgery may be safe for many adults, less so for some children.

Johns Hopkins Children's Center investigators report active children are prone to further knee cartilage tears while awaiting repair surgery after ACL injury

Lack of Belief in Body's Ability to Function Through Pain Linked to Daily Pre-Surgery Prescribed Opioid Use Among Candidates for Elective Spine Surgery

Researchers discovered a link between pain self-efficacy and preoperative opioid use among patients seeking elective spine surgery

Walking a Leashed Dog Associated with Risk of Traumatic Brain Injury Among Adults

Researchers found that women, and adults age 65 and older, were more likely to sustain serious injuries, such as fractures and TBIs, as a result of walking a leashed dog

Research Labs

Our orthopaedic research division and its faculty members are recognized internationally as leading innovators in musculoskeletal science and training. Our investigators conduct basic, translational and clinical research in topics that represent the great diversity of problems that impact the musculoskeletal system. Focus areas include integrative musculoskeletal biology, stem cells and regenerative medicine, skeletal neurobiology, bone metastasis and clinical outcomes.

Komatsu Lab

Principal Investigator

Masanobu Komatsu PhD

Research Areas

• Drug targeting
• High endothelial venules and their role in lymphocyte recruitment
• Tertiary lymphoid structure (TLS) in cancer
• Vascular normalization

Spine Outcomes Research Center

Richard Leroy Skolasky ScD

• orthopaedics

Innovation in Spine Surgery

Orthopaedic spine surgeon Khaled Kebaish discusses the latest innovations and research in the spine division at the Johns Hopkins Department of Orthopaedic Surgery.

Recent Publications

Predicting Major Complications and Discharge Disposition After Adult Spinal Deformity Surgery

Surgical Setting in Achilles Tendon Repair: How Does It Relate to Costs and Complications?

Predicting Risk of 30-day Postoperative Morbidity Using the Pathologic Fracture Mortality Index

The Use of Weakly Supervised Machine Learning for Necrosis Assessment in Patients with Osteosarcoma: A Pilot Study

Is Delayed Anterior Cruciate Ligament Reconstruction Associated with a Risk of New Meniscal Tears? Reevaluating a Longstanding Paradigm

Cutting edge topics and advances in orthopaedic research

Edward Schwarz and Jay Lieberman

Implantable sensor technology: measuring bone and joint biomechanics of daily life in vivo

Stresses and strains are major factors influencing growth, remodeling and repair of musculoskeletal tissues. Therefore, knowledge of forces and deformation within bones and joints is critical to gain insight i...

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Biologic adjuvants for fracture healing

Bone tissue has an exceptional quality to regenerate to native tissue in response to injury. However, the fracture repair process requires mechanical stability or a viable biological microenvironment or both t...

Atypical subtrochanteric femoral shaft fractures: role for mechanics and bone quality

Bisphosphonates are highly effective agents for reducing osteoporotic fractures in women and men, decreasing fracture incidence at the hip and spine up to 50%. In a small subset of patients, however, these age...

Platelet-rich plasma therapy - future or trend?

Chronic complex musculoskeletal injuries that are slow to heal pose challenges to physicians and researchers alike. Orthobiologics is a relatively newer science that involves application of naturally found mat...

Recent advances in shoulder research

Shoulder pathology is a growing concern for the aging population, athletes, and laborers. Shoulder osteoarthritis and rotator cuff disease represent the two most common disorders of the shoulder leading to pai...

Early diagnosis to enable early treatment of pre-osteoarthritis

Osteoarthritis is a prevalent and disabling disease affecting an increasingly large swathe of the world population. While clinical osteoarthritis is a late-stage condition for which disease-modifying opportuni...

Orthopedics

Building on a long history of patient-driven innovation, our physicians and scientists continue to push the boundaries of discovery for better diagnosis and care, such as state-of-the-art gait studies in the Motion Analysis Laboratory of Kenton R. Kaufman, Ph.D., P.E.

For nearly a century, the Division of Orthopedic Surgery Research at Mayo Clinic has worked to improve outcomes and quality of life for both adult and pediatric patients with musculoskeletal disorders.

Once problems are identified in the clinic, our physicians and scientists take them to the laboratory bench for study, and the results are then translated back into clinical practice, where they directly benefit patients. Our investigators secure research grants to support their work, conduct clinical trials, run basic research laboratories and train future generations of researchers, and many also provide patient care.

In the Division of Orthopedic Surgery Research, we're pushing scientific boundaries to find more opportunities to improve the well-being of our patients. Advances in molecular medicine, genomics and proteomics allow us to investigate revolutionary new treatments for conditions that affect the musculoskeletal system, including arthritis, cancer, sports injuries, traumatic amputations, and bone and joint problems.

Musculoskeletal diseases and musculoskeletal trauma affect hundreds of millions of people around the world and cost billions of dollars to treat, with visits to emergency rooms, medical offices and specialists.

Our commitment to do better for our patients isn't new. In 1927, a Mayo Clinic orthopedist was the first to describe the pathological events that lead to compartment syndrome. In the 1940s, another orthopedist was among the first to design metal plates to fix fractures securely. In 1970, a Mayo Clinic orthopedist was the first in the United States to implant an artificial hip joint. A joint registry started decades ago provides a wealth of information that informs research and treatment still today. Mayo Clinic orthopedists have also pioneered treatments for bone cancer, complex wrist injuries and injuries to children's growing bones, and have developed artificial joints for every major joint.

Today, some of our research focus areas include:

• Regeneration of bone and cartilage.
• Motion analysis.
• Tissue engineering.
• Elbow disorders.

As part of the Department of Orthopedic Surgery, our research division leverages the wealth of expertise offered by a multidisciplinary faculty, fostering a collaborative environment that extends the scope of orthopedic research. Together, we continue the drive to expand and enhance clinical, basic and translational research activities.

Apply For the Unmatched Medical Student Program

Unmatched medical students can apply from March 15 to April 12, 2024 , for a one-year research fellowship. Get the details about this excellent research opportunity.

In the Division of Orthopedic Surgery Research, we're pushing scientific boundaries to find more opportunities to improve diagnosis and treatment for patients. Contact us about our research, about potential collaboration and training opportunities, or about making a philanthropic gift.

Our research team continues to build on a decades-long foundation of discovery, advancing knowledge about joint, bone and tendon disorders, arthritis, biomechanics, motion analysis, spine problems, scoliosis, amputation, and more.

Your Scoliosis Journey Research Study

This research study aims to better understand the experience of the patient and family during treatment for scoliosis and to determine which decision-making tools are best to facilitate treatment options.

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• Frontiers in Bioengineering and Biotechnology
• Biomechanics
• Research Topics

Biomechanics in Orthopaedic Diseases and Surgery

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The mechanical environment of the musculoskeletal system plays a fundamental role in orthopaedic diseases. Understanding the magnitude, pattern, and duration of biomechanical factors and how they impact surgical treatment is an ongoing topic of interest in biomechanics. However, the way forces and stresses ...

Keywords : biomechanics, orthopaedic, treatment, disease progression, osseous tissue, rehabilitation

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Virtual Sessions and Webinars

Attend engaging discussions by experts in the field of orthopaedics by registering for the upcoming ors virtual scientific session, "incorporating undergraduates in your research program" on may 15, 2024. ors members are welcome to register at no charge., call for fracture repair abstracts, the ors international section of fracture repair (isfr) and the ota basic science focus forum (bsff) will collaborate for a joint session at the ota (orthopaedic trauma association) annual meeting, october 21 - 23 in montréal, canada. submit your abstracts by may 20, 2024., registration open for tendon conference 2024, join us for the ors tendon conference 2024: mechanism to therapy - emerging technologies and therapeutic outcomes, taking place may 30 - june 1 at the mayo clinic in rochester, mn. registration closes on may 22, 2024., 2024 annual meeting photo gallery, feeling nostalgic take a look at our online photo gallery to relive your favorite moments of the 2024 annual meeting. your colleagues, presentations, or favorite sessions may be featured, new investigator toolkit, learn online, on demand, and at your own pace with the newly launched new investigator toolkit from learnors. this career development course brings together early and mid-career investigators for panel discussions on the development of critical "soft skills", including cultivating mentoring skills, building your lab brand, and strategic planning across various career stages., upcoming 2024 events, don't miss out on exciting opportunities in the orthopaedic community. mark your calendars for these ors upcoming events. find details for each event by clicking the link below., ors 70th t-shirts now available to order, get your own limited edition, commemorative ors 70 years advancing research to keep the world moving t-shirt. this is a great way to share your support for ors and your enthusiasm for musculoskeletal research., for 70 years, the orthopaedic research society has been the leading research society supporting engineers, orthopaedic surgeons, biologists, veterinarians, and clinicians in pursuit of a world without musculoskeletal limitations. learn more.

The ORS continues to bring together the best researchers and surgeons in the world and gives them a community to share new research findings, discuss new ideas and to collaborate in new and innovative ways. The ORS offers programs that teach, mentor and encourage our members while inspiring them to move the field of orthopaedic research forward.

The ORS looks forward to welcoming you to our research community!

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• Open access
• Published: 14 June 2021

The future of basic science in orthopaedics and traumatology: Cassandra or Prometheus?

• Henning Madry 1 ,
• Susanne Grässel 2 ,
• Ulrich Nöth 3 ,
• Borna Relja 4 ,
• Anke Bernstein 5 ,
• Denitsa Docheva 6 ,
• Max Daniel Kauther 7 ,
• Jan Christoph Katthagen 8 ,
• Rainer Bader 9 ,
• Martijn van Griensven 10 ,
• Dieter C. Wirtz 11 ,
• Michael J. Raschke 8 &
• Markus Huber-Lang   ORCID: orcid.org/0000-0003-2359-6516 12  

European Journal of Medical Research volume  26 , Article number:  56 ( 2021 ) Cite this article

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Orthopaedic and trauma research is a gateway to better health and mobility, reflecting the ever-increasing and complex burden of musculoskeletal diseases and injuries in Germany, Europe and worldwide. Basic science in orthopaedics and traumatology addresses the complete organism down to the molecule among an entire life of musculoskeletal mobility. Reflecting the complex and intertwined underlying mechanisms, cooperative research in this field has discovered important mechanisms on the molecular, cellular and organ levels, which subsequently led to innovative diagnostic and therapeutic strategies that reduced individual suffering as well as the burden on the society. However, research efforts are considerably threatened by economical pressures on clinicians and scientists, growing obstacles for urgently needed translational animal research, and insufficient funding. Although sophisticated science is feasible and realized in ever more individual research groups, a main goal of the multidisciplinary members of the Basic Science Section of the German Society for Orthopaedics and Trauma Surgery is to generate overarching structures and networks to answer to the growing clinical needs. The future of basic science in orthopaedics and traumatology can only be managed by an even more intensified exchange between basic scientists and clinicians while fuelling enthusiasm of talented junior scientists and clinicians. Prioritized future projects will master a broad range of opportunities from artificial intelligence, gene- and nano-technologies to large-scale, multi-centre clinical studies. Like Prometheus in the ancient Greek myth, transferring the elucidating knowledge from basic science to the real (clinical) world will reduce the individual suffering from orthopaedic diseases and trauma as well as their socio-economic impact.

Introduction

Orthopaedic and trauma research is a gateway to better health and mobility, reflecting the ever-increasing and complex burden of musculoskeletal diseases and injuries. The field of basic science in orthopaedics and traumatology grows not only in Germany, but also across Europe and worldwide. Questions asked from orthopaedic and trauma surgeons to scientists who are involved in the many facets of musculoskeletal research and vice versa represent the exciting basis of fruitful interactions within this specific field.

Orthopaedic and trauma research is the key competence of the Basic Science Section (“ Sektion Grundlagenforschung ”, SGF) of the German Society for Orthopaedics and Trauma Surgery (“ Deutsche Gesellschaft für Orthopädie und Unfallchirurgie ”, DGOU). The SGF represents a multidisciplinary community of orthopaedic and trauma surgeons, biologists, biochemists, engineers, and veterinarians. Its members are devoted to orthopaedic and trauma research and aid in defining nationwide research policies in orthopaedics and trauma surgery through close cooperation of the corresponding committees and groups with the DGOU. Within the SGF, three networks exist, each of which has a specific focus: the network of musculoskeletal regeneration (MR-Net), the network of musculoskeletal biomechanics (MSB-Net), and the network for trauma research (NTF). The SGF plays also a key role in bringing together researchers, surgeons and other clinicians at the German Congress for Orthopaedics and Trauma Surgery (“ Deutscher Kongress für Orthopädie und Unfallchirurgie ”, DKOU). This annual meeting is considered the most important congress in the field of Orthopaedics and Traumatology in Germany and far beyond as it represents the largest of its sector in Europe with more than 10,000 attendees. At the annual congress, the SGF is responsible for organizing the basic research lectures and scientific poster sessions. Furthermore, the SGF is involved in the selection process of the recipient of the prestigious Basic Research Prize and honours outstanding scientific work with the annual Wilhelm Roux Award and several poster prizes, all of which are awarded during the common meeting.

Besides these national and global research efforts, more and more basic science questions arise which need to be addressed. However, far beyond the orthopaedic and trauma context, the lack of basic knowledge had been challenged already in ancient Greece by Prometheus who, endued with the highest degree of intelligence, brought the “fire” and “light” into the darkness of the human mind. An etymological analysis of the word “pro metheus” suggests that it derives from the Greek word Προμηθεύς, meaning “forethought” and “plan ahead”. Thus, Prometheus could function as a role model for the basic scientist in the field of orthopaedics and traumatology: by a wise study planning with a focussed standardized setting, the scientist is capable to enlighten enigmatic mechanisms, all of which may finally result in an adequate and satisfactory treatment of the patient (Fig.  1 ). In accordance, mechanism-driven trials, in which basic science-revealed specific mechanisms are targeted, are proposed to be more likely to show improvement in a heterogeneous trauma cohort [ 1 ]. On the other hand, basic science is also endangered to play the imposed role of Cassandra, the tragic Greek priestess who could accurately foresee the future but sadly was never believed. In free association, many basic research efforts and exciting findings will never make it to the bedside because they are neither perceived nor apprehended by the clinical-, funding- (Fig.  2 ), and political stakeholders and thus remain neglected. In this regard, during all stages of the career of both the scientist and clinician, a common language and understanding of the basic scientist and the clinician is often missing or underdeveloped. In case of the academic surgeon in the dual role as clinician and basic scientist, a framework has been proposed to accomplish the patient-centred trilogy of clinic, research, and teaching with a high degree of reliability and room for scientific and personal development [ 2 ]. In the case of the surgical/medical scientist such a dual role is rare but conceivable [ 3 ] and its further development is forward-looking (“pro-metheus”) and probably game changing. However, care has to be taken that such a medical scientist is not seen as a Cassandra. The balance between applied science and ethical medical treatment is delicate and needs to be guarded.

The Prometheus paradigm. The societies for orthopaedics and traumatology need to identify and define problems of the patient suffering from orthopaedic or (post)traumatic problems, which are so far diagnostically and therapeutically not satisfactorily resolved. Then, based on the “Prometheus” principle, a highly intelligent and innovative idea, evolved in the interdisciplinary discourse, may lead to a perfectly designed basic science study to reveal the underlying mechanisms. This can be realized, e.g. by a translational study with appropriate in vitro or in vivo (animal) modelling. The gained knowledge can then be translated back to the clinic and subsequently be evaluated for the final benefit of the patient

The Cassandra challenge. Disproportion of the high incidence as well as impact of orthopaedic diseases and trauma as opposed to the funding resources in the corresponding fields. In accordance to the “Cassandra” principle, the basic research societies in orthopaedics and traumatology might point to this imbalance without being heard by the surrounding environment and society—although they crusade for an improved quality of life and for improving the clinical outcome of the affected patients

Orthopaedic and trauma research have overlapping interests, but some differences exist as well. Nevertheless, both fields are closely intertwined and therefore considered here. This paper addresses, from the different viewpoints of both orthopaedics and traumatology, the need of basic science, provides examples of cutting-edge research topics, elaborates on evolving methodologies to reach the state-of-the art, supports the need for high-quality animal research, and aims to define hot scientific topics and urgent needs that will have to be answered in the near and far future.

Past research efforts in orthopaedics and traumatology: Cassandra or Prometheus?

The field of orthopaedics and traumatology addresses all musculoskeletal aspects of body support and motion. For example, a major task is the care for high-impact degenerative diseases such as osteoarthritis (OA) that challenge health-care systems globally. OA represents a high-burden non-communicable disease (NCD), its numbers significantly increase in terms of total burden and age-standardized disability-adjusted life-years (DALY), which considerably rose between 1990 and 2015 [ 4 ]. The hallmark of OA is the breakdown of the articular cartilage, although OA also affects all other tissues related to a joint. For many patients, pain and the slow and often immeasurable reduction in joint function are the main indicators of the disease and therefore also of the key to any potential conservative or surgical therapy. Orthopaedic research and treatment of OA has experienced significant advances over the past decades. Already in the 1960s it became clear that while pain may be relieved by intraarticularly injecting steroids, this treatment does not address cartilage loss and can even be harmful to the articular cartilage [ 5 ]. The discovery of growth factors, dating even back to the middle of the past century [ 6 ], was a crucial step as it led to the identification of factors that stimulate the articular chondrocytes to proliferate and to deposit extracellular matrix. This development can be regarded as a shining beacon enlightening orthopaedic and trauma research in the spirit of Prometheus, the mythological figure reflecting the quest for scientific truth and knowledge. The very first animal study on the effect of growth factors for cartilage repair conducted at the Charité hospital in Berlin was published in 1980 [ 7 ]. Nearly four decades later, the principle of applying growth factors for cartilage repair was finally tested in randomized-controlled clinical trials to potentially modify structural and clinical features of OA. The data revealed reductions in the loss of cartilage thickness over time when compared with placebo, however, without significant reduction in OA pain or other clinical parameters [ 8 ]. These extremely intriguing outcomes raise a number of burning questions to be addressed in the future; most importantly on the clinical relevance of such long searched-for structural changes and how to conduct future clinical trials of disease-modifying drugs that demonstrate effects not only on structure, but also on the clinical endpoints that matter to the patients [ 9 ]. This dilemma was already reflected by the classical remark of Henry Mankin, the renowned orthopaedic clinician scientist, who stated that the “cartilage does not yield its secrets easily, inducing cartilage to heal is not simple, … and progression to OA is sometimes so slow that we delude ourselves into thinking we are doing better than we are” [ 10 ]. Novel approaches for OA are being pursued to overcome this challenge, among which detailed investigation of topographical changes [ 11 ], OA pain [ 7 , 8 ] and possibly contributing environmental factors [ 12 ], while also advancing gene-based [ 13 ] and other targeted approaches [ 14 ] as future therapies.

The field of trauma addresses any individuum since physical trauma can hit anybody and affect any region of the body at any time. Thus, trauma represents a major global burden of the past, presence and future [ 15 ]. Based on the highly interconnected organ systems (e.g. lung–liver, bone–kidneys, neuro-immune system) tissue injury to even a single bone or organ may affect via complex pathophysiological mechanisms various other tissues and thus in principle the whole body [ 16 , 17 ]. Therefore, the field of trauma research comprises the whole human organism—from the first change on the sub-molecular level to the clinical bedside reality and far beyond into the society. As consequence, this cosmic broadness can barely be covered by the trauma research efforts of one nation, nor European- or even world-wide. Thus, trauma-related science has been attributed to be arbitrary, unfocused, fragmented and reduced quality research [ 18 ]. In clinical translation, numerous poorly designed studies have been performed, which addressed emergency, surgical and critical care management in various trauma settings with the main result: an urgent need for state-of-the art meaningful clinical studies remains and is further called for, especially to fill the gaps of corresponding guidelines [ 19 , 20 , 21 ]. However, clinical studies in trauma are rather complex and difficult to perform not at least due to the vast heterogeneity of trauma conditions, -patterns and -care [ 18 ]. Thereby, large numbers of patients need to be included to achieve statistically sound results. The involved pathomechanisms, which drive the healing and rehabilitation processes after trauma and in orthopaedics but also any complication directly associated with the quality of life, allegorize a “black box”, which is difficult to enlighten in a reasonable scientific, ethical and economic manner. Basic research in principle is capable to enlighten this “black box” of unknown mechanisms and provide the scientific rationale for an improved design of translational, clinically meaningful studies. These studies will return important insights in complex interactions and adjust the scientific models, which can subsequently be optimized.

However, it is also important not only to set the focus on external factors and trends affecting the evolution of trauma research but also to address—more alike blind Casandra’s approach—internal factors. Therefore, we should also question what could the field have done differently in the past and can we learn from other research disciplines? In this regard, uncertain career development paths for basic and clinical scientist in our field, ongoing separation of bench and bedside research, reduced industry–academic interactions, discouragement of innovative thinking, insufficient transdisciplinary networking, short-term research endeavours, as well as reserved public dissemination of meaningful results represent internal obstacles decelerating past and probably also present research efforts.

Current hot topics in orthopaedics and traumatology

Since the areas of basic research within the field of orthopaedics and traumatology are numerous and steadily growing, only exemplary current hot topics can be delineated here.

In bone fracture healing, after initial inflammation, new cartilage and bone matrices are deposited that result in connecting the fracture ends. Currently, the recruitment of skeletal progenitor cells, vascular cells and subtypes of immune cells during the repair process as well as the direct, cell-to-cell and secretory cross-talk between exogenous and endogenous cells is extensively investigated [ 22 ]. Immunomodulation of musculoskeletal repair represents a very attractive area for novel therapeutic strategies: research efforts can lead to the identification of possible ways to spatio-temporal modulate specific immune cells to beneficially steer the repair process [ 23 , 24 ]. Studies on the tight interplay of vascular, inflammatory and metabolic cascades during fracture healing are increasing [ 25 ]. Research in this area is critical to clarify the intimately intertwined cascades of tissue regeneration. Mesenchymal stromal cells (MSCs) represent also important immunomodulators, as they arise naturally at damaged sites but also when applied in a therapeutic approach. Regarding intercellular communication, current research addresses cellular exchange or even therapeutic application via extracellular vesicles [ 26 , 27 ]. A current review on extracellular vesicles in musculoskeletal pathologies and regeneration serves as a timely example of a scientific network that is actively supported by the DGOOC [ 28 ]. Extracellular vesicles can also contain micro-RNAs that have been shown to be involved in many musculoskeletal diseases [ 29 , 30 , 31 ].

Regeneration of cartilage after trauma remains a hot topic since articular cartilage has a very poor capacity to repair itself and if healing occurs through fibrocartilage, it is characterized by insufficient structural and biomechanical properties. A better understanding of the cellular and molecular mechanisms of chondrocyte differentiation, phenotype preservation and the simultaneous response of chondrocytes to biochemical and biomechanical stress [ 32 , 33 , 34 ], may here provide insights into mechanisms that can guide chondrocytes and MSCs towards stable articular cartilage formation [ 35 , 36 , 37 ], which reflects the contemplations in the introduction about the impact of OA on the field of orthopaedics.

The awareness of the investigators on tendon, ligament, fascia and meniscal repair is also expanding towards understanding the intrinsic capacities of these tissues to heal [ 38 ] and the cell sources that participate in their repair [ 38 , 39 , 40 , 41 , 42 , 43 , 44 ]. Another fascinating exploratory field is on clarifying the impact of matrix composition, topography and biophysical properties onto the cells [ 45 , 46 ]. Several recent studies have reported interesting novel data on the contribution of different cell types [ 47 , 48 , 49 , 50 , 51 , 52 , 53 ] as well as on the instructiveness of matrix properties on cell behaviour [ 46 , 52 , 54 , 55 ].

Since it affects countless patients worldwide, intervertebral disc (IVD) regeneration is another basic science focus. Experimental studies explored the performance of different cell types when injected in IVDs [ 56 , 57 , 58 ]. Although there are significant advances in the basic understanding of IVD regeneration, this area is still in its prime and far from clinical translation when, for example, compared with the articular cartilage research. Since the IVD is a multilayered anatomical structure, namely nucleus pulposus, annulus fibrosus and the cartilage endplate, successful regeneration will require a simultaneous revival of all three tissues or functionally integrated in one implant [ 59 ]. Therefore, further basic research is needed on characterizing the molecular and cellular composition in homeostasis and degeneration of this unique structure [ 58 , 60 ].

The orthopaedic and trauma fields have also recognized that repair proceeds at a different pace in young and healthy versus aged and degenerated/co-morbidity plagued musculoskeletal tissues and organs. Robust work has demonstrated that cellular niches and their endogenous progenitor cells have a profound impact during the age-related degenerative process [ 49 , 61 ]. Hence, therapeutic principles have to be attuned to satisfactorily restore the structure–function of aged and injured tissues in the elderly. However, the search for the “fountain of youth” seems Prometheus-like, whereas Casandra may propose never to find such a source.

The mechano-biological pairing and the biophysics of cell–matrix interactions are essential in understanding the progression of musculoskeletal diseases and can also empower tissue regeneration. However, if these stimuli become abnormal they can prevent restoration and rather aggravate the disease. Current topics of interest within experimental orthopaedic biomechanics include mechanical testing of normal and diseased musculoskeletal tissues [ 62 , 63 ], medical implant design and testing [ 64 ], tissue engineering [ 65 , 66 , 67 ] and translation of biomechanical into biochemical signals [ 68 , 69 , 70 , 71 ]. This research area will further optimize the biomechanical parameters of tissue-engineered implants and better understand cell- and drug-based therapeutic effects on mechanical behaviour at the tissue-level. In regard to tissue engineering, current biomaterial-related hot topics are “smarter” materials that are both degradable and able to control, steer or modulate biological responses and processes [ 72 , 73 ]. The role of extracellular matrix in instructing biochemical cascades in cells has become rather evident [ 74 , 75 ]. Also, materials that can closely mimic natural tissue properties and can navigate stem cell fates or exert immunomodulatory features are considered cutting edge [ 71 ]. The progress in developing such next generation biomaterials, that embrace the three-dimensional complexity of regenerating tissues as well as the interplay and optimal integration into the host tissue, can revolutionize biomaterial strategies in the near future.

With the rapid evolution of high-throughput, digital and information technologies, implementing system-oriented approaches to study musculoskeletal tissues, their diseases and repair processes become more and more realistic. In bone, the different cell subpopulations are well characterized. However, in cartilage, tendon, ligament, meniscus, and IVD, very interesting findings indicate an unexpected heterogeneity of cell subpopulations in these tissues (based on single cell RNA sequence data) [ 43 , 48 ]. This may shift our understanding of the pathogenesis based on transition and prevalence of specific cell types during disease processes. Such research may result in defining cell subclasses that could be targeted to ameliorate disease progression versus cell types that can augment regeneration.

Another focus is set on platelets, especially after severe trauma. Platelets are fundamental to primary hemostasis, but become profoundly dysfunctional after polytrauma by unknown mechanisms, contributing to acute coagulopathy, severe bleeding and mortality. Circulating platelets are transformed into procoagulant balloons within minutes after trauma, and can release large numbers of activated microparticles/extracellular vesicles which coat leukocytes [ 76 ]. Furthermore, this study reports that the injury-induced danger molecule release (histone H4) functions as a driver of the procoagulant ballooning and subsequent innate immune response.

Concerning microvesicles (MVs), a recent study suggests that burn injury generates MVs, which allow skin keratinocytes to disperse bioactive substances. Applying diverse pharmacologic and genetic tools indicates that the optimal release of MVs is dependent upon the platelet-activating factor receptor [ 77 ]. Furthermore, MVs seem essential for transportation of metabolically labile bioactive lipids as cargo from cells in response to environmental stress. An important role of MVs concerning the complement C5a–C5aR1 axis was suggested in severely traumatized patients as well. C5a-induced MVs shedding from neutrophils decreased C5aR1 surface expression, while on the other hand profound inflammatory signals were induced, which may represent a key driver of the neutrophil dysfunction post trauma [ 78 ].

Trauma-induced emergency hematopoiesis characterizes the dramatic increase in the hematopoietic demand on the bone marrow to replace effector leukocytes upon their consumption during the inflammatory response to infection or injury. In experimental polytrauma, emergency hematopoiesis is mechanistically driven by the IL-1/MyD88/G-CSF-dependent pathway, resulting in the expansion of hematopoietic as well as myeloid-skewed and multipotent progenitor cells [ 79 ]. Furthermore, the role of specific inflammatory leukocyte subsets is currently ever broadened. In a trauma-induced sepsis model, endogenous intrinsic anti-inflammatory signals seem crucial to modulate the early monocyte/macrophages-driven inflammation by modifying their subset distributions [ 80 ]. In the clinical setting, the immunosuppressive properties of a neutrophil subtype (CD16 high CD62L low ) are gaining attention as causative and surrogate markers for increased susceptibility to infections post trauma [ 81 ].

Chronic inflammation in the elderly (“inflamm-aging”) has been proposed as major contributor to the decline in the regenerative capacity of the skeleton [ 82 ], mainly caused by skeletal stem/progenitor cell (SSPC) dysfunction [ 83 ]. A systemic and local proinflammatory environment was the major contributor of the decline in SSPC number and function resulting in cellular senescence [ 83 ]. Concerning muscle injury and regeneration, a metabolic cross-talk between macrophages and satellite cells has been defined, in which macrophage-derived glutamine preserves the function of satellite cells and thus provide a promising target [ 84 ].

Concerning remote organ injury after severe trauma, development of trauma-induced acute kidney injury (TRAKI) represents a role model for the impact of the immuno-pathophysiological trauma response [ 17 ]. In an ischaemia–reperfusion model of TRAKI single nucleus RNA sequencing of the kidneys allowed the characterization of various cell states during repair from acute injury: in the proximal tubule, a specific proinflammatory and profibrotic cell state was found that fails to repair [ 85 ]. “Full regeneration after amputation” could reflect a myth from Prometheus. However, in the ever exciting adult axolotl limb regeneration model, a novel regeneration-specific mitochondria-related cell cluster was discovered, and musculoskeletal cell populations supporting regeneration by providing energy were defined by modern tools (e.g. large-scale single-cell RNA sequencing and reconstructions of the dynamic single-cell transcriptome) [ 86 ].

Traumatic brain injury (TBI) is the strongest environmental risk factor for the accelerated development of neurodegenerative processes. Computational modelling provided insights into the cognitive decline and the presence of neurofibrillary tangles of the protein tau in the brains upon repetitive TBI [ 87 ]. The impacting high-strain rate deformation alone could induce tau mislocalization to dendritic spines and synaptic deficits in cultured hippocampal neurons which was inhibitable on the signalling level [ 87 ]. Thus, a mechanistic pathway directly relating mechanical deformation of neurons to tau-mediated synaptic impairments and a potential exploitable therapeutic approach to improve repetitive TBI consequences has now been provided [ 87 ]. A recently described molecular memory system (C–C-chemokine receptor type 5 (CCR5) signalling) was tested for its role in recovery after TBI [ 88 ]. Genetic and small molecule-based perturbation of CCR5 promotes functional recovery from TBI with preservation of dendritic spines and new patterns of cortical projections to contralateral pre-motor cortex [ 88 ]. Recently, the anti-inflammatory cytokine interleukin 13 (IL-13) was reported to accelerate functional recovery in murine TBI [ 89 ]. Furthermore, IL-13 reduced neuronal tissue loss, preserved white matter integrity, ameliorated the elevation of proinflammatory factors and reduced the number of proinflammatory microglia/macrophages after TBI [ 89 ]. Thus, IL-13 may present a potential immunotherapy to promote long-term recovery from TBI.

An interesting TBI model for basic science was developed and extensively characterized in Drosophila. Precise compression of the head using a piezoelectric actuator inflicts mild, moderate, or severe brain trauma in this Drosophila TBI model and provides a powerful tool to study the genetic system due to many conserved genes and pathways [ 90 ]. This tunable TBI model recapitulates mammalian injury phenotypes with severity-dependent ataxia, life span reduction, brain degeneration, cognitive decline and transient glial dysfunction. This model showed also stimulation of antioxidant, proteasome, and chaperone activity and thus underscores the ability of the stress response to mitigate TBI-induced brain degeneration [ 90 ].

Evolving the methodology to reach the state-of-the art in orthopaedics and traumatology

The clinical care of orthopaedic and trauma patients in Germany can be classified as being at a state-of-the art level to which basic and applied medical and surgical research has significantly contributed. As mentioned above, a major disease burden in the orthopaedic field comes from OA, an age-related and/or trauma-induced multi-factorial, slowly progressing and primarily non-inflammatory degenerative disorder of the synovial joints culminating in the irreversible destruction of the articular cartilage [ 91 ]. The underlying molecular mechanisms have been addressed by basic research since many years. Breakdown of the collagen fibrillar network is a hallmark of cartilage extracellular matrix (ECM) degradation in OA [ 92 , 93 ]. In this context, characterization of collagen triple helical domain structure, fragments thereof and folding mechanisms and kinetics was a basic research focus four to five decades ago. Commonly applied methods to do so were trypsin and pepsin digestion, SDS-PAGE, spectrophotometric measurements of triple helix formation, optical rotation and circular dichroism of collagen chains [ 94 , 95 ]. Chromatography based on DEAE cellulose and amino acid composition analysis after HCl driven hydrolysis were common methods to characterize the molecular composition of collagen chains [ 96 , 97 ]. This research focus on the molecular structure of collagens was followed by genetic based approaches, e.g. in the 1990s by the use of genetically modified mouse strains. Major methodologies to characterize the function and role of collagens and associated non-collagenous proteins in cartilage matrix integrity and turnover were skeletal staining, (immuno-)histochemical assays, in situ hybridization, TUNEL, SDS-PAGE and western blotting and ultrastructural analysis [ 98 , 99 , 100 ]. These methods were completed by northern blotting and RT-PCR-based gene expression analysis, biochemical methods such as application of recombinantly produced ECM proteins, solid phase binding assays, immunoprecipitation, immunoelectron- and immunofluorescence microscopy and 3D chondrocyte cell culture models. In addition, genetically modified mouse models for refined analysis of cartilage ECM proteins were designed [ 101 , 102 , 103 , 104 ].

Since the last two decades, high-end imaging methodology as atomic force microscopy (AFM), micro computed tomography (µCT) and nanoCT became more and more important for biomechanical and microstructural analysis of cartilage and (subchondral) bone. Indentation-type (IT) AFM is particularly useful to determine elastic properties of the chondrocyte pericellular matrix and cartilage ECM and the most sensitive method for detecting minute changes in cartilage biomechanics [ 105 , 106 , 107 , 108 ]. µCT application for topographical analysis of pathological structural changes of the osteochondral unit in translational animal models is state of the art [ 11 ]. To observe microstructural changes, i.e. in micro-channels in the subchondral bone zone and in the calcified cartilage zone, nanoCT analysis as high-end imaging modality is the preferred choice [ 107 , 109 ]. In this line, the spatial organization of chondrocytes and its potential role in cartilage functioning and physiology became of special interest as reorganization and destruction of the basic spatial pattern during OA is important for responding to mechanical forces [ 110 ].

Increasing attention received the field of cartilage regeneration by employing chondrocytes, MCSs or recently chondrocyte progenitor cells (CPC), the latter residing in the articular cartilage. Regarding this focus, characterization of chondrogenic phenotype and chondrogenic differentiation capacity of MSCs and CPCs was of crucial importance. Sophisticated 3D cell culture techniques as cell pellet cultures, culture in alginate beads or fibrin/agarose gels were developed and refined together with the optimization of cell culture medium in order to maintain the chondrogenic phenotype and prevent dedifferentiation. One research group focused especially on chondrogenic differentiation of MSC and refinement of appropriate 3D culture systems [ 111 , 112 , 113 , 114 ]. Early key contributions on 3D culture of chondrocytes in order to prevent dedifferentiation and to keep the chondrogenic phenotype focused on the culture of chondrocytes in agarose [ 115 , 116 ] and alginate beads [ 117 , 118 ]. Identification of CPC (or MPC) in OA cartilage and their isolation, and establishing culture regimens was already described as early as 2004 [ 119 ] followed some years later by more extended work on the regenerative potential of CPCs [ 120 , 121 ].

The genetic manipulation of MSCs became an attractive approach to produce therapeutic platforms for translational settings that aim at restoring articular cartilage defects. For that, gene transfer methods received increasing attention in order to improve the chondrogenic phenotype or proper differentiation of chondrocytes and progenitor cells. It was first reported in 2003 that AAV-based vectors can efficiently transduce and stably express foreign genes in articular chondrocytes, including chondrocytes of normal and osteoarthritic human articular cartilage, and MSC [ 122 ]. Numerous publications followed with ever-increasing refinement of gene delivery to the target cells/tissue [ 123 , 124 , 125 ]. Recent work focussed on delivery of therapeutic genes using specific biomaterial composites as scaffold-assisted gene therapy is considered as a highly promising tool to treat articular cartilage lesions upon direct delivery of chondrogenic candidate gene sequences [ 126 , 127 ].

Concerning nationwide (trauma-)surgery-related research, a detailed survey was conducted in 1992 [ 128 ]. It revealed that the basic topics in the past mainly addressed transplantation immunology, implant biocompatibility, regulation of cell growth, control of of bone and cartilage growth, and sources of pain. Since then, a lot has changed and the importance of molecular biology for traumatology has steadily increased [ 129 , 130 , 131 , 132 ]. So far, main methods in surgical research addressed in principle three classical fields: in vitro, in vivo, and in real life, reflected by modern molecular biology-based methods [ 133 , 134 ], animal experiments [ 135 , 136 , 137 , 138 ], and clinical studies, respectively [ 139 ]. The methodical spectrum in the field of molecular biology is immense, and novel, highly sophisticated methods are constantly added. Based on their widespread acceptance these serve today as a basic tool-box, including vectors for DNA cloning, restriction endonucleases and DNA hybridization, southern blotting, PCR, DNA sequencing and of course the analysis of highly polymorphic markers. For RNA analysis, Northern blotting, PCR, RT-PCR, qPCR, RT-qPCR, and, since a few years ago the digital droplet PCR (ddPCR) [ 140 ] are applied. Further methods are the transfection of eukaryotic cells, protein analysis, DNA cloning, gene mapping and identification, to name but a few. More complex cell cultures such as organ culture models and organoid models are utilized. New imaging methods like µCT, FIB-ESEM, TEM, CLEM, and live cell imaging also contributed to a better spatial resolution and understanding of posttraumatic degeneration and regeneration processes. With the help of molecular markers and the use of antibodies, e.g. also in GMP quality, it is now possible to mark cells and to trace their path within the body.

Moreover, with the help of numerical simulation tools, the behaviour of implants under different loading scenarios and microenvironments can also be predicted. The simulation includes the Finite Element Method (FEM) as well as multi-body simulations (MBS). While FEM is mainly used for field problems such as stress and strain calculations, implant micromovements as well as biological (re)modelling processes, MBS is used for dynamic problems such as gait analyses, investigation of muscle and joint forces or joint kinematics. Frequently in collaborative efforts with industrial partners, new implants have been developed and their design adapted to the respective clinical requirements [ 141 ]. Furthermore, surgical techniques have improved considerably in recent years [ 142 ]. Perioperative and rehabilitation quality management and evidence-based medicine have also found their way into surgical research [ 143 , 144 , 145 ].

New focal points in basic research have been established, e.g. in polytrauma research [ 146 , 147 ], biomechanics on macroscopic [ 148 , 149 ] and microscopic levels [ 150 , 151 ], osteoimmunology [ 16 , 152 ], and soft tissue- and wound healing [ 153 ]. Moreover, disturbance factors such as age [ 154 , 155 , 156 ] as well as co-morbidities [ 129 , 157 ] such as diabetes, osteoporosis and obesity have been added to reflect a more realistic picture. Furthermore, promoting minimal invasiveness, recently, probe-based confocal laser-endomicroscopy combined with artificial intelligence (AI)-supported quantitative spatial data has been introduced in a proof-of-principle study as non-destructive optical biopsy to clinically detect early disease detection [ 158 ].

Together, these exemplary points indicate a paradigm shift in orthopaedic and trauma surgery research from pure clinical towards more basic research efforts to generate an improved understanding of the underlying mechanisms in trauma, inflammation, regeneration, degeneration, and repair processes. Based on a better micro- and molecular understanding, new diagnostic and therapeutic approaches will be developed and to be proven clinically.

Why animal research in orthopaedics and traumatology?

In one traditional myth, Prometheus established the form of animal sacrifice practised in the ancient Greek religion. Such a sacrifice had been performed not only as service for a worshipped divinity, but also to accomplish some forseeing, i.e. to identify hidden truth and to predict the future from the appearance of inner organs. Thus, it is tempting to speculate that Prometheus was in some favour for animal research. In contrast, Cassandra could represent a person beset by doubt about the importance of animal research, but unheard by the surrounding people and society.

In translation to current orthopaedic and trauma research, both positions are advocated: pro- and anti-animal research although strict opponents to meaningful animal research remain a minority. However, it is undisputed that, like the German Research Foundation (DFG), orthopaedic and trauma research in Germany is committed to animal welfare and scientific validity and thus pursues the 3R principles [ 159 ]: replacement, reduction and refinement of animal experiments.

The necessity of animal modelling in trauma research is mainly deduced and justified by the complexity of the in vivo response to trauma and investigations on novel therapeutic interventions. In this regard, even the usage of organ-on-the chip technology and comptautional study designs cannot fully model the posttraumatic in vivo situation. Furthermore, the research of trauma-specific management, such as specific operation techniques or early resuscitation strategies and subsequent critical care are so far problematic (or even impossible) to model with the help of in vitro or in silico systems. Nevertheless, in the past, the validity of trauma modelling of clinical reality was questioned, e.g. in regard to genetic responses [ 160 ]. However, the murine models investigated indeed lacked a high simulation quality of the clinical setting. Therefore, multiple efforts have been undertaken to closer simulate the real world in trauma, burn and sepsis research [ 161 ] including international expert consensus initiatives to improve animal modelling [ 162 ] addressing among others the principle of “refinement”. Moreover, the use of a mouse- or pig intensive care unit seems to provide a higher degree of clinical simulation, validity and reliability [ 138 , 163 ]. Furthermore, the better definition of the inflicted injury on well-defined anatomical regions helps to standardize the injury pattern and thus provides a better if not superior comparison with specific human situations [ 164 ]. Another development towards translational validity is the increasing consideration of various co-morbidities and their adequate modelling such as diabetes, osteoporosis, smoking, alcohol, atherosclerosis or chronic obstructive pulmonary disease in the context of trauma [ 165 , 166 , 167 ].

In the musculoskeletal system, delicate interactions between molecular, cellular, tissue and biomechanical levels exist that can only be incompletely modelled using for example computer-based systems (in silico) or in in vitro models. The need of animal research in orthopaedics may be exemplary highlighted by the cautionary tale of meniscal lesions and their close relationship to the articular cartilage and subchondral bone. The medial and lateral menisci -crescent shaped wedges of fibrocartilage located between the femoral condyles and the tibial plateau- perform important tasks to transmit loads and stabilize the knee joint [ 168 ]. Some hundred years ago, the menisci were regarded as functionless remnants of intraarticular leg muscles [ 169 ] and, consequently, they have been treated until the second decade of the last century with total meniscectomy. However, orthopaedic surgeons soon realized that such meniscectomized knees rapidly developed OA [ 170 ]. As this phenomenon can precisely be reproduced in both small and large animal models [ 171 ], it could have been foreseen if such studies would have been conducted before excising menisci in patients. Subsequently, techniques of meniscal refixation, repair, transplantation and replacement were evaluated and more and more refined over time with the ultimate goal of OA prevention [ 172 , 173 ]. This narrative is in principle also related to the thalidomide disaster that caused numerous horrific birth defects in the human and that could have been prevented by more extensive preclinical testing in laboratory animals [ 174 ].

Today, the intricate relationship between meniscus, cartilage, bone, cruciate ligaments and others has developed into an entirely new field of research [ 175 ]. Although in vitro models immensely helped to elucidate molecular mechanisms and pathways involved in meniscal pathophysiology, the effect of a loss of meniscal tissue on the adjoining tissues and complex interactions within a biomechanically functional knee joint cannot be recapitulated. It is the testing of such clinically relevant interactions in (large) animal models that can help to elucidate these, often, intricate relationships. As a large animal knee joint is similar to that of humans in terms of joint anatomy, biomechanical function, cartilage and subchondral bone morphology [ 168 ], arthroscopic inspections and even reconstructive surgical interventions such as meniscal repair can be performed. Moreover, the postoperative course may be followed over relatively long periods, thus providing clinically relevant data that can only insufficiently be obtained by, for example, using a three-dimensional bioreactor culture with external forces applied.

In regard to “reduction” of animal experiments, orthopaedic and trauma research in Germany, Europe and worldwide has undertaken multiple efforts. An important step has been the formation of national networks such as the network for trauma research (NTF) or international research groups such as the Translational Large Animal Research Network (TREAT). These collaborative groups design, apply and perform common small and large animal studies and finally share tissues on a multi-organ level for synchronically answering different hypotheses. This results in an enormous reduction in animal numbers as if each hypothesis would have been investigated separately at each institution. For example, one recent pig study run by the TREAT group provided material for more then 10 collaborating research groups [ 176 ]. Similar efforts are undertaken at the trauma department at Aachen University [ 177 , 178 ] or at the trauma collaborative research centre (CRC1149) at Ulm where multiple groups share organs from one mouse experiment. We consider these best practise examples of maximal reduction of animal numbers, performed at expert centres and shared by multiple clinical and basic researchers.

Concerning “replacement”, various ex vivo and in silico studies investigating interacting systems such as whole blood [ 179 ] or fracture healing [ 180 , 181 ] are ongoing innovative developments even for first simulations of therapeutic principles. Furthermore, the publishing culture has changed not only in the field of orthopaedics and trauma research e.g. by following the ARRIVE guidelines and exact reporting of the experimental conditions [ 182 ]. Leading journals in the field endorse the use of the ARRIVE guidelines [ 183 , 184 ]. The basic scientist in the field of orthopaedics and trauma is also encouraged to compare the results from the corresponding animal models with clinical reality to assess to which extend they match, e.g. immune and organ profiling in murine versus clinical polytrauma or to translate important scientific discoveries from the bench-to the operation theatre and back within the complex environment of the musculoskeletal system [ 185 , 186 ]. Of course, in this research, the 3Rs principle must always be taken into account [ 159 ].

Taken together, basic research in orthopaedics and traumatology remains a valuable, important column of clinically meaningful research and is certainly committed to animal welfare and scientific validity.

Future aims of basic science in orthopaedics and traumatology

In the near future, basic science in orthopaedics and traumatology will also be impacted by the revolution of technological improvement in materials and methods, especially due to computer-assisted techniques and a rapidly growing digitalization. On-site 3D printing technologies will be transferred to traumatology for research, education, and generation of individual (personalized) implants [ 187 ]. Due to the great variability of materials for 3D printing, further indication of this technology will be the treatment of bone and soft tissue defects with individually printed scaffolds [ 188 ]. Improvements in molecular imaging will increase the understanding of musculoskeletal pathologies. In the next ten years, artificial intelligence (AI) will be most likely introduced into clinical use in radiology and diagnostic imaging for the detection and classification of fractures and multiply injured patients [ 189 ]. Therefore, large databases for the use of AI have to be assembled and scientifically evaluated as AI will be a key feature in patient care in orthopaedics and traumatology. Trauma and implant registries will profit from digitalization with direct transfer of data leading to a more reliable quality. While established trauma registries lead to an improvement in outcome and quality assurance in major trauma in the last decade (e.g. CT in emergency room [ 190 ], prehospital intubation [ 191 ], prehospital tranexamic acid [ 192 ], future registries will focus on the ageing society (e.g. AltersTraumaRegister DGU) as the orthopaedic trauma surgeon will see less (young) multiply injured cases but an increasing number of geriatric patients. This will also need to be taken into account in in vitro studies [ 192 ]. The understanding and the treatment of sepsis and trauma associated immune-modulation will focus on the ageing patient as well [ 193 ]. As osteoporosis and malignant osteolysis will lead to an increasing number of pathologic fractures, finite element models for fracture prevention have to be introduced and evaluated as the CT-scan will be an increasingly used diagnostic tool for the geriatric patient in the future [ 194 ]. Hot topics of musculoskeletal regeneration will be tissue engineering of soft tissue i.e. muscle, tendon, cartilage and bone and their respective transitions [ 45 , 195 ] with a focus on stem cells and extracellular vesicles [ 196 ] as well as further research on biodegradable implants and their clinical results. Biomechanical research will deal with the modulation of implant-derived debris, improvement of implant design and the application of gait analysis in the prevention of sports injuries.

In contrast to the revolution of new technologies and devices derived from basic science in orthopaedics and traumatology, the evolution in clinical life appears to be at a somewhat slower pace. Some authors claim that there is a stagnation in clinical translation of already known biomaterials, surface modifications and antimicrobial strategies for the control of biomaterial-implant-associated infections that has to be changed [ 197 ]. A challenge of clinical research in traumatology is the large variety of patients (e.g. fracture type, soft tissue damage, infection, age, bone quality, activity level, co-morbidities) with increasing treatment options offered by basic science (e.g. implant design, material, approach, molecular theragnostics) with a limited caseload, even in large centres. Therefore, international, industry-independent randomized-controlled trials have to prove the clinical relevance of new and existing devices and therapies on the market that derived from basic science.

What structures do we need in the future?

Experts, progeny, money, and time—it could be as easy as this. But what are the real challenges and goals of orthopaedic and trauma research in the future?” Tempora mutantur, nos et mutamur in illis ” which means that time is changing and changes us within: on the one hand the population is ageing, osteoporosis persists, fractures are becoming even more fragile; on the other hand, diagnostic means, treatment modalities and implant development are rapidly evolving. Digitalization as well as augmented and virtual reality will more and more become part of clinically relevant research and care. Nonetheless, the future of basic science in orthopaedics and traumatology primarily depends on the fascination of future young scientists and clinicians to join our exciting field. We will need to find the right way to inspire medical and natural science students early on for basic science in musculoskeletal research. Modern and contemporary working conditions will help to keep this research field competitive. We should not make the mistake to rely on past achievements but seek for concepts allowing for more protected research time.

A current barrier is sparse funding opportunities for orthopaedic and trauma research. Local intramural research programmes realized at several universities in Germany provide some benevolent start-up funding for young investigators. However, to date national and international research funding only offer limited opportunities to recruit larger peer-reviewed third-party funds due to a high demand but reduced supply. This gap will increase even more in the near future with EU funds for reseach in times of pandemic challenges considerably cut [ 198 ]. While the recent race for a vaccine during COVID-19 pandemic showed that EU countries are stronger if united than separated, the fact that (at the time of submitting this work) the United States added USD 10 billion since May 2020 to health crisis funding while the EU agreed in summer 2020 on slightly over USD 3 billion puts a spotlight on the importance and socio-economic impact of financial support for science [ 199 ]. The significance of understanding the pathomechanism of degeneration and injury and the need for high-end biomechanical research including modern robotic and simulation solutions must result in manifold funding options. Especially European funding for degenerative musculoskeletal and trauma research is largely missing. Excellent ideas of highly motivated and brilliant young investigators should be supported to boost future careers with lower funding threshold and without the need to prove extended preliminary work. The goal should be an easier entrance to the basic science world. In principle, such a path is proposed for “primary” applications at the German Research Foundation (DFG) but rarely established at other funding organizations.

These, together with fading industrial support, represent the “typical” means of funding that are known and used for decades. In other societal areas, other types of funding exist and are successful. Scientists in orthopaedics and trauma surgery should therefore seek to optimize their funding through these modern and creative funding possibilities. One can think of crowdfunding [ 200 , 201 ] or setting up specific charity funds dedicated to orthopaedic and trauma research. Of course ethical and privacy issues needs to be taken into consideration [ 202 , 203 ]. To enhance the effects of such funding strategies, the scientists should also enhance their exposure and outreach with a special emphasis on societal impact.

Although there will always be outstanding individuals—together we are stronger. Therefore, funding tools should also focus on support of research networks working on overarching questions and out of the box solutions. There must be a stimulus for cooperative research groups ( 18 ) such as the aforementioned initiatives like NTF, TREAT, MR-Net, MSB-Net, etc., rather than sole competition of few groups working in an isolated manner. Such cooperative efforts should be built up not just nationally but also European-wide or even globally.

Thereby, it should be strived for to develop an infrastructure for optimization of well-designed experimental animal studies by communicating planned projects prior to the start and invite external parties to participate. This may result in enhanced handling with the 3Rs and add to the translational value of studies as it may not only inspire groups already involved in basic science but also groups normally focussing on clinical work as well. Finally, also options should be explored to integrate projects with other (related and less-related) fields of research such as immunology, chronic inflammation, (cardio)-vascular research and identify in which trends (such as organoids and AI), the field lies behind.

The representatives of the umbrella organizations such as the SGF, DGOU, DGU, and DGOOC should further strengthen their work hand in hand to bring experts, progeny, money, and time for basic science in orthopaedics and traumatology and thereby in a long term to the patient care.

Orthopaedic and trauma research in Germany, Europe- and world-wide gets a Cassandra-like, disproportional attention of funding in comparison to its relevance, to its importance for the individuum and socio-economic impact of related diseases and traumata (Fig.  2 ). Basic science in these fields addresses the whole conceivable spatio-temporal dimension of a human life with high-end structure–function tools. For the future, further development of networks and collaborative work, facilitated by overarching groups such as the SGF, help the multidisciplinary communities to define the urgent needs and research foci. Exciting new discoveries from the various fields of basic research will be translated from the laboratory to the clinical “real world”. Orthopaedic and trauma research should overcome any remaining boundaries between basic research and clinical reality, innovation and implementations in treatment, open research questions and available funding. The future of basic science in these fields can only be mastered by carefully listening to each other and intensified care for a common language between basic scientists and clinicians for a deeper understanding of the clinical mechanisms and therapeutic opportunities. Prioritized future projects will need to address a broad range of opportunities from AI, nano-technologies to large-scale, multi-centric clinical studies. Furthermore, Prometheus-like novel dissemination strategies to bring the light of basic science not only to the bedside but also into the awareness of society are mandatory. Only then, quality of life of the individual, suffering from orthopaedic diseases or trauma, and the global society will benefit from basic science efforts. Now is the time to act and to provide excellent and visionary programmes that will ensure the bright future of basic science in orthopaedics and traumatology.

Availability of data and materials

Not applicable since review.

Change history

29 october 2021.

The open access funding note was missing from this article and should have read ‘’Open Access funding enabled and organized by Projekt DEAL’’

Doppenberg EMR, Choi SC, Bullock R. Clinical trials in traumatic brain injury: lessons for the future. J Neurosurg Anesthesiol. 2004;16(1):87–94.

Article   PubMed   Google Scholar  

Huber-Lang M, Neugebauer E. The dual role of academic surgeons as clinicians and researchers—an attempt to square the circle? Patient Saf Surg. 2011;22(5):16.

Article   Google Scholar  

Schyma BM, Cole E, Wren SM, Brohi K, Brundage SI. Delivering trauma mastery with an international trauma masters. Injury. 2019;50(4):877–82.

GBD 2015 DALYs and HALE Collaborators. Global, regional, and national disability-adjusted life-years (DALYs) for 315 diseases and injuries and healthy life expectancy (HALE), 1990–2015: a systematic analysis for the Global Burden of Disease Study 2015. Lancet Lond Engl. 2016;388(10053):1603–58.

Mankin HJ, Conger KA. The acute effects of intra-articular hydrocortisone on articular cartilage in rabbits. J Bone Joint Surg Am. 1966;48(7):1383–8.

Article   CAS   PubMed   Google Scholar  

Levi-Montalcini R. The nerve growth factor 35 years later. Science. 1987;237(4819):1154–62.

Jentzsch KD, Wellmitz G, Heder G, Petzold E, Buntrock P, Oehme P. A bovine brain fraction with fibroblast growth factor activity inducing articular cartilage regeneration in vivo. Acta Biol Med Ger. 1980;39(8–9):967–71.

CAS   PubMed   Google Scholar  

Hochberg MC, Guermazi A, Guehring H, Aydemir A, Wax S, Fleuranceau-Morel P, et al. Effect of intra-articular sprifermin vs placebo on femorotibial joint cartilage thickness in patients with osteoarthritis: the FORWARD randomized clinical trial. JAMA. 2019;322(14):1360–70.

Article   CAS   PubMed   PubMed Central   Google Scholar  

Katz JN, Neogi T, Callahan LF, Block JA, Conaghan PG, Simon LS, et al. Disease modification in osteoarthritis; pathways to drug approval. Osteoarthr Cartil Open. 2020;2(2):100059.

Mankin HJ. Chondrocyte transplantation—one answer to an old question. N Engl J Med. 1994;331(14):940–1.

Oláh T, Reinhard J, Gao L, Goebel LKH, Madry H. Reliable landmarks for precise topographical analyses of pathological structural changes of the ovine tibial plateau in 2-D and 3-D subspaces. Sci Rep. 2018;8(1):75.

Article   PubMed   PubMed Central   CAS   Google Scholar  

Berenbaum F, Wallace IJ, Lieberman DE, Felson DT. Modern-day environmental factors in the pathogenesis of osteoarthritis. Nat Rev Rheumatol. 2018;14(11):674–81.

Cucchiarini M, Madry H. Biomaterial-guided delivery of gene vectors for targeted articular cartilage repair. Nat Rev Rheumatol. 2019;15(1):18–29.

Latourte A, Kloppenburg M, Richette P. Emerging pharmaceutical therapies for osteoarthritis. Nat Rev Rheumatol. 2020;16(12):673–88.

Mokdad AH, Forouzanfar MH, Daoud F, Mokdad AA, El Bcheraoui C, Moradi-Lakeh M, et al. Global burden of diseases, injuries, and risk factors for young people’s health during 1990–2013: a systematic analysis for the Global Burden of Disease Study 2013. Lancet Lond Engl. 2016;387(10036):2383–401.

Huber-Lang M, Lambris JD, Ward PA. Innate immune responses to trauma. Nat Immunol. 2018;19(4):327–41.

Messerer DAC, Halbgebauer R, Nilsson B, Pavenstädt H, Radermacher P, Huber-Lang M. Immunopathophysiology of trauma-related acute kidney injury. Nat Rev Nephrol. 2020. https://doi.org/10.1038/s41581-020-00344-9 .

Manson J, Thiemermann C, Brohi K. Trauma alarmins as activators of damage-induced inflammation. Br J Surg. 2012;99(Suppl 1):12–20.

Korompilias AV, Lykissas MG, Vekris MD, Beris AE, Soucacos PN. Microsurgery for lower extremity injuries. Injury. 2008;39(Suppl 3):S103-108.

Schuster K, Davis K, Hernandez M, Holena D, Salim A, Crandall M. American Association for the Surgery of Trauma emergency general surgery guidelines gap analysis. J Trauma Acute Care Surg. 2019;86(5):909–15.

Somerson JS, Stein BA, Wirth MA. Distribution of high-volume shoulder arthroplasty surgeons in the United States: data from the 2014 medicare provider utilization and payment data release. J Bone Joint Surg Am. 2016;98(18):e77.

Herrmann M, Jakob F. Bone marrow niches for skeletal progenitor cells and their inhabitants in health and disease. Curr Stem Cell Res Ther. 2019;14(4):305–19.

Haffner-Luntzer M, Foertsch S, Fischer V, Prystaz K, Tschaffon M, Mödinger Y, et al. Chronic psychosocial stress compromises the immune response and endochondral ossification during bone fracture healing via β-AR signaling. Proc Natl Acad Sci U S A. 2019;116(17):8615–22.

Wendler S, Schlundt C, Bucher CH, Birkigt J, Schipp CJ, Volk H-D, et al. Immune Modulation to enhance bone healing—a new concept to induce bone using prostacyclin to locally modulate immunity. Front Immunol. 2019;10:713.

Loi F, Córdova LA, Pajarinen J, Lin T, Yao Z, Goodman SB. Inflammation, fracture and bone repair. Bone. 2016;86:119–30.

Malda J, Boere J, van de Lest CHA, van Weeren PR, Wauben MHM. Extracellular vesicles—new tool for joint repair and regeneration. Nat Rev Rheumatol. 2016;12(4):243–9.

Pishavar E, Copus JS, Atala A, Lee SJ. Comparison study of stem cell-derived extracellular vesicles for enhanced osteogenic differentiation. Tissue Eng Part A. 2020. https://doi.org/10.1089/ten.tea.2020.0194 .

Herrmann M, Diederichs S, Melnik S, Riegger J, Trivanović D, Li S, et al. Extracellular vesicles in musculoskeletal pathologies and regeneration. Front Bioeng Biotechnol. 2021;8:624096.

Article   PubMed   PubMed Central   Google Scholar  

Kelch S, Balmayor ER, Seeliger C, Vester H, Kirschke JS, van Griensven M. miRNAs in bone tissue correlate to bone mineral density and circulating miRNAs are gender independent in osteoporotic patients. Sci Rep. 2017;7(1):15861.

Seeliger C, Balmayor ER, van Griensven M. miRNAs Related to Skeletal Diseases. Stem Cells Dev. 2016;25(17):1261–81.

Seeliger C, Karpinski K, Haug AT, Vester H, Schmitt A, Bauer JS, et al. Five freely circulating miRNAs and bone tissue miRNAs are associated with osteoporotic fractures. J Bone Miner Res Off J Am Soc Bone Miner Res. 2014;29(8):1718–28.

Article   CAS   Google Scholar  

Leyh M, Seitz A, Dürselen L, Schaumburger J, Ignatius A, Grifka J, et al. Subchondral bone influences chondrogenic differentiation and collagen production of human bone marrow-derived mesenchymal stem cells and articular chondrocytes. Arthritis Res Ther. 2014;16(5):453.

Pattappa G, Zellner J, Johnstone B, Docheva D, Angele P. Cells under pressure - the relationship between hydrostatic pressure and mesenchymal stem cell chondrogenesis. Eur Cell Mater. 2019;06(37):360–81.

Pattappa G, Krueckel J, Schewior R, Franke D, Mench A, Koch M, et al. Physioxia expanded bone marrow derived mesenchymal stem cells have improved cartilage repair in an early osteoarthritic focal defect model. Biology. 2020;9(8):230.

Article   CAS   PubMed Central   Google Scholar  

Cucchiarini M, Asen A-K, Goebel L, Venkatesan JK, Schmitt G, Zurakowski D, et al. Effects of TGF-β overexpression via rAAV gene transfer on the early repair processes in an osteochondral defect model in minipigs. Am J Sports Med. 2018;46(8):1987–96.

Diederichs S, Klampfleuthner FAM, Moradi B, Richter W. Chondral differentiation of induced pluripotent stem cells without progression into the endochondral pathway. Front Cell Dev Biol. 2019;7:270.

Venkatesan JK, Moutos FT, Rey-Rico A, Estes BT, Frisch J, Schmitt G, et al. Chondrogenic differentiation processes in human bone-marrow aspirates seeded in three-dimensional-woven poly(ɛ-Caprolactone) scaffolds enhanced by recombinant adeno-associated virus-mediated SOX9 gene transfer. Hum Gene Ther. 2018;29(11):1277–86.

Klatte-Schulz F, Minkwitz S, Schmock A, Bormann N, Kurtoglu A, Tsitsilonis S, et al. Different achilles tendon pathologies show distinct histological and molecular characteristics. Int J Mol Sci. 2018;19(2):404.

Article   PubMed Central   CAS   Google Scholar  

Dex S, Alberton P, Willkomm L, Söllradl T, Bago S, Milz S, et al. Tenomodulin is required for tendon endurance running and collagen I fibril adaptation to mechanical load. EBioMedicine. 2017;5(20):240–54.

Kronenberg D, Michel PA, Hochstrat E, Wei M, Brinckmann J, Müller M, et al. Increased collagen turnover impairs tendon microstructure and stability in integrin α2β1-deficient mice. Int J Mol Sci. 2020;18(21):2835.

Lin D, Alberton P, Caceres MD, Volkmer E, Schieker M, Docheva D. Tenomodulin is essential for prevention of adipocyte accumulation and fibrovascular scar formation during early tendon healing. Cell Death Dis. 2017;8(10):e3116–e3116.

Schneider M, Angele P, Järvinen TAH, Docheva D. Rescue plan for Achilles: therapeutics steering the fate and functions of stem cells in tendon wound healing. Adv Drug Deliv Rev. 2018;129:352–75.

Sun H, Wen X, Li H, Wu P, Gu M, Zhao X, et al. Single-cell RNA-seq analysis identifies meniscus progenitors and reveals the progression of meniscus degeneration. Ann Rheum Dis. 2020;79(3):408–17.

Zellner J, Pattappa G, Koch M, Lang S, Weber J, Pfeifer CG, et al. Autologous mesenchymal stem cells or meniscal cells: what is the best cell source for regenerative meniscus treatment in an early osteoarthritis situation? Stem Cell Res Ther. 2017;8(1):225.

Font Tellado S, Balmayor ER, Van Griensven M. Strategies to engineer tendon/ligament-to-bone interface: Biomaterials, cells and growth factors. Adv Drug Deliv Rev. 2015;1(94):126–40.

Yin H, Strunz F, Yan Z, Lu J, Brochhausen C, Kiderlen S, et al. Three-dimensional self-assembling nanofiber matrix rejuvenates aged/degenerative human tendon stem/progenitor cells. Biomaterials. 2020;236:119802.

Harvey T, Flamenco S, Fan C-M. A Tppp3+Pdgfra+ tendon stem cell population contributes to regeneration and reveals a shared role for PDGF signalling in regeneration and fibrosis. Nat Cell Biol. 2019;21(12):1490–503.

Kendal AR, Layton T, Al-Mossawi H, Appleton L, Dakin S, Brown R, et al. Multi-omic single cell analysis resolves novel stromal cell populations in healthy and diseased human tendon. Sci Rep. 2020;10(1):13939.

Kohler J, Popov C, Klotz B, Alberton P, Prall WC, Haasters F, et al. Uncovering the cellular and molecular changes in tendon stem/progenitor cells attributed to tendon aging and degeneration. Aging Cell. 2013;12(6):988–99.

Moser HL, Abraham AC, Howell K, Laudier D, Zumstein MA, Galatz LM, et al. Cell lineage tracing and functional assessment of supraspinatus tendon healing in an acute repair murine model. J Orthop Res Off Publ Orthop Res Soc. 2020. https://doi.org/10.1002/jor.24769 .

Asai S, Otsuru S, Candela ME, Cantley L, Uchibe K, Hofmann TJ, et al. Tendon progenitor cells in injured tendons have strong chondrogenic potential: the CD105-negative subpopulation induces chondrogenic degeneration. Stem Cells Dayt Ohio. 2014;32(12):3266–77.

Tarafder S, Brito JA, Minhas S, Effiong L, Thomopoulos S, Lee CH. In situ tissue engineering of the tendon-to-bone interface by endogenous stem/progenitor cells. Biofabrication. 2019;12(1):015008.

Yin Z, Hu J-J, Yang L, Zheng Z-F, An C-R, Wu B-B, et al. Single-cell analysis reveals a nestin+ tendon stem/progenitor cell population with strong tenogenic potentiality. Sci Adv. 2016;2(11):e1600874.

Font Tellado S, Bonani W, Balmayor ER, Foehr P, Motta A, Migliaresi C, et al. Fabrication and characterization of biphasic silk fibroin scaffolds for tendon/ligament-to-bone tissue engineering. Tissue Eng Part A. 2017;23(15–16):859–72.

Font Tellado S, Chiera S, Bonani W, Poh PSP, Migliaresi C, Motta A, et al. Heparin functionalization increases retention of TGF-β2 and GDF5 on biphasic silk fibroin scaffolds for tendon/ligament-to-bone tissue engineering. Acta Biomater. 2018;72:150–66.

Lyu F-J, Cheung KM, Zheng Z, Wang H, Sakai D, Leung VY. IVD progenitor cells: a new horizon for understanding disc homeostasis and repair. Nat Rev Rheumatol. 2019;15(2):102–12.

Sakai D, Andersson GBJ. Stem cell therapy for intervertebral disc regeneration: obstacles and solutions. Nat Rev Rheumatol. 2015;11(4):243–56.

Sakai D, Grad S. Advancing the cellular and molecular therapy for intervertebral disc disease. Adv Drug Deliv Rev. 2015;84:159–71.

Teixeira GQ, Boldt A, Nagl I, Pereira CL, Benz K, Wilke H-J, et al. A Degenerative/proinflammatory intervertebral disc organ culture: an ex vivo model for anti-inflammatory drug and cell therapy. Tissue Eng Part C Methods. 2016;22(1):8–19.

Lin D, Alberton P, Delgado Caceres M, Prein C, Clausen-Schaumann H, Dong J, et al. Loss of tenomodulin expression is a risk factor for age-related intervertebral disc degeneration. Aging Cell. 2020;19(3):e13091.

Jakob F, Ebert R, Rudert M, Nöth U, Walles H, Docheva D, et al. In situ guided tissue regeneration in musculoskeletal diseases and aging : Implementing pathology into tailored tissue engineering strategies. Cell Tissue Res. 2012;347(3):725–35.

Lakin BA, Snyder B, Grinstaff M. Assessing cartilage biomechanical properties: techniques for evaluating the functional performance of cartilage in health and disease. Annu Rev Biomed Eng. 2017;19:27–55.

Morgan EF, Unnikrisnan GU, Hussein AI. Bone mechanical properties in healthy and diseased states. Annu Rev Biomed Eng. 2018;04(20):119–43.

Petersen A, Princ A, Korus G, Ellinghaus A, Leemhuis H, Herrera A, et al. A biomaterial with a channel-like pore architecture induces endochondral healing of bone defects. Nat Commun. 2018;9(1):4430.

Bothe F, Deubel A-K, Hesse E, Lotz B, Groll J, Werner C, et al. Treatment of focal cartilage defects in minipigs with zonal chondrocyte/mesenchymal progenitor cell constructs. Int J Mol Sci. 2019;20(3):653.

Dalton PD, Woodfield TBF, Mironov V, Groll J. Advances in hybrid fabrication toward hierarchical tissue constructs. Adv Sci. 2020;7(11):1902953.

Hauptstein J, Böck T, Bartolf-Kopp M, Forster L, Stahlhut P, Nadernezhad A, et al. Hyaluronic acid-based bioink composition enabling 3d bioprinting and improving quality of deposited cartilaginous extracellular matrix. Adv Healthc Mater. 2020;1:9.

Google Scholar  

Dai EN, Heo S-J, Mauck RL. ‘Looping in’ mechanics: mechanobiologic regulation of the nucleus and the epigenome. Adv Healthc Mater. 2020;9(8):e2000030.

Haffner-Luntzer M, Liedert A, Ignatius A. Mechanobiology of bone remodeling and fracture healing in the aged organism. Innov Surg Sci. 2016;1(2):57–63.

PubMed   PubMed Central   Google Scholar  

Peredo AP, Jo YK, Duan G, Dodge GR, Lee D, Mauck RL. Mechano-activated biomolecule release in regenerating load-bearing tissue microenvironments. Biomaterials. 2021;265:120255.

Steppe L, Liedert A, Ignatius A, Haffner-Luntzer M. Influence of low-magnitude high-frequency vibration on bone cells and bone regeneration. Front Bioeng Biotechnol. 2020;8:595139.

Freedman BR, Mooney DJ. Biomaterials to mimic and heal connective tissues. Adv Mater Deerfield Beach Fla. 2019;31(19):e1806695.

Özkale B, Sakar MS, Mooney DJ. Active biomaterials for mechanobiology. Biomaterials. 2021;267:120497.

Article   PubMed   CAS   Google Scholar  

Morejón L, Delgado JA, Antunes Ribeiro A, de Varella Oliveira M, Mendizábal E, García I, et al. Development, characterization and in vitro biological properties of scaffolds fabricated from calcium phosphate nanoparticles. Int J Mol Sci. 2019;20(7):1790.

Schwarz S, Koerber L, Elsaesser AF, Goldberg-Bockhorn E, Seitz AM, Dürselen L, et al. Decellularized cartilage matrix as a novel biomatrix for cartilage tissue-engineering applications. Tissue Eng Part A. 2012;18(21–22):2195–209.

Vulliamy P, Gillespie S, Armstrong PC, Allan HE, Warner TD, Brohi K. Histone H4 induces platelet ballooning and microparticle release during trauma hemorrhage. Proc Natl Acad Sci U S A. 2019;116(35):17444–9.

Liu L, Fahy KE, Awoyemi AA, Thapa P, Kelly LE, Chen J, et al. Thermal burn injury generates bioactive microvesicles: evidence for a novel transport mechanism for the lipid mediator platelet-activating factor (PAF) that involves subcellular particles and the PAF receptor. J Immunol. 2020;205:193–201.

Karasu E, Demmelmaier J, Kellermann S, Holzmann K, Köhl J, Schmidt CQ, et al. Complement C5a induces pro-inflammatory microvesicle shedding in severely injured patients. Front Immunol. 2020. https://doi.org/10.3389/fimmu.2020.01789/full .

Fuchs A, Monlish DA, Ghosh S, Chang S-W, Bochicchio GV, Schuettpelz LG, et al. Trauma induces emergency hematopoiesis through IL-1/MyD88–dependent production of G-CSF. J Immunol. 2019;202(10):3020–32.

Janicova A, Becker N, Xu B, Wutzler S, Vollrath JT, Hildebrand F, et al. Endogenous uteroglobin as intrinsic anti-inflammatory signal modulates monocyte and macrophage subsets distribution upon sepsis induced lung injury. Front Immunol. 2019;10:2276.

Janicova A, Relja B. Neutrophil phenotypes and functions in trauma and trauma-related sepsis. Shock. 2020. https://doi.org/10.1097/SHK.0000000000001695 .

Oh J, Lee YD, Wagers AJ. Stem cell aging: mechanisms, regulators and therapeutic opportunities. Nat Med. 2014;20(8):870–80.

Josephson AM, Bradaschia-Correa V, Lee S, Leclerc K, Patel KS, Muinos Lopez E, et al. Age-related inflammation triggers skeletal stem/progenitor cell dysfunction. Proc Natl Acad Sci U S A. 2019;116(14):6995–7004.

Shang M, Cappellesso F, Amorim R, Serneels J, Virga F, Eelen G, et al. Macrophage-derived glutamine boosts satellite cells and muscle regeneration. Nature. 2020;587(7835):626–31.

Kirita Y, Wu H, Uchimura K, Wilson PC, Humphreys BD. Cell profiling of mouse acute kidney injury reveals conserved cellular responses to injury. Proc Natl Acad Sci. 2020;117(27):15874–83.

Qin T, Fan C-M, Wang T-Z, Sun H, Zhao Y-Y, Yan R-J, et al. Single-cell RNA-seq reveals novel mitochondria-related musculoskeletal cell populations during adult axolotl limb regeneration process. Cell Death Differ. 2020;4:1606.

Braun NJ, Yao KR, Alford PW, Liao D. Mechanical injuries of neurons induce tau mislocalization to dendritic spines and tau-dependent synaptic dysfunction. Proc Natl Acad Sci U S A. 2020;117(46):29069–79.

Joy MT, Ben Assayag E, Shabashov-Stone D, Liraz-Zaltsman S, Mazzitelli J, Arenas M, et al. CCR5 is a therapeutic target for recovery after stroke and traumatic brain injury. Cell. 2019;176(5):1143-1157.e13.

Miao W, Zhao Y, Huang Y, Chen D, Luo C, Su W, et al. IL-13 ameliorates neuroinflammation and promotes functional recovery after traumatic brain injury. J Immunol Baltim Md 1950. 2020;204(6):1486–98.

CAS   Google Scholar  

Saikumar J, Byrns CN, Hemphill M, Meaney DF, Bonini NM. Dynamic neural and glial responses of a head-specific model for traumatic brain injury in Drosophila. Proc Natl Acad Sci U S A. 2020;117(29):17269–77.

Grässel S, Muschter D. Recent advances in the treatment of osteoarthritis. Res. 2020;9:325.

Goldring MB, Goldring SR. Osteoarthritis. J Cell Physiol. 2007;213(3):626–34.

Goldring MB, Goldring SR. Articular cartilage and subchondral bone in the pathogenesis of osteoarthritis. Ann N Y Acad Sci. 2010;1192:230–7.

Bächinger HP, Bruckner P, Timpl R, Engel J. The role of cis-trans isomerization of peptide bonds in the coil leads to and comes from triple helix conversion of collagen. Eur J Biochem. 1978;90(3):605–13.

Bächinger HP, Bruckner P, Timpl R, Prockop DJ, Engel J. Folding mechanism of the triple helix in type-III collagen and type-III pN-collagen. Role of disulfide bridges and peptide bond isomerization. Eur J Biochem. 1980;106(2):619–32.

Brandt A, Glanville RW, Hörlein D, Bruckner P, Timpl R, Fietzek PP, et al. Complete amino acid sequence of the N-terminal extension of calf skin type III procollagen. Biochem J. 1984;219(2):625–34.

Timpl R, Bruckner P, Fietzek P. Characterization of pepsin fragments of basement membrane collagen obtained from a mouse tumor. Eur J Biochem. 1979;95(2):255–63.

Aszódi A, Bateman JF, Hirsch E, Baranyi M, Hunziker EB, Hauser N, et al. Normal skeletal development of mice lacking matrilin 1: redundant function of matrilins in cartilage? Mol Cell Biol. 1999;19(11):7841–5.

Aszódi A, Chan D, Hunziker E, Bateman JF, Fässler R. Collagen II is essential for the removal of the notochord and the formation of intervertebral discs. J Cell Biol. 1998;143(5):1399–412.

Hagg R, Hedbom E, Möllers U, Aszódi A, Fässler R, Bruckner P. Absence of the alpha1(IX) chain leads to a functional knock-out of the entire collagen IX protein in mice. J Biol Chem. 1997;272(33):20650–4.

Blumbach K, Niehoff A, Paulsson M, Zaucke F. Ablation of collagen IX and COMP disrupts epiphyseal cartilage architecture. Matrix Biol J Int Soc Matrix Biol. 2008;27(4):306–18.

Budde B, Blumbach K, Ylöstalo J, Zaucke F, Ehlen HWA, Wagener R, et al. Altered integration of matrilin-3 into cartilage extracellular matrix in the absence of collagen IX. Mol Cell Biol. 2005;25(23):10465–78.

Nicolae C, Ko Y-P, Miosge N, Niehoff A, Studer D, Enggist L, et al. Abnormal collagen fibrils in cartilage of matrilin-1/matrilin-3-deficient mice. J Biol Chem. 2007;282(30):22163–75.

Schmitz M, Niehoff A, Miosge N, Smyth N, Paulsson M, Zaucke F. Transgenic mice expressing D469Delta mutated cartilage oligomeric matrix protein (COMP) show growth plate abnormalities and sternal malformations. Matrix Biol J Int Soc Matrix Biol. 2008;27(2):67–85.

Danalache M, Kleinert R, Schneider J, Erler AL, Schwitalle M, Riester R, et al. Changes in stiffness and biochemical composition of the pericellular matrix as a function of spatial chondrocyte organisation in osteoarthritic cartilage. Osteoarthritis Cartilage. 2019;27(5):823–32.

Hartmann B, Marchi G, Alberton P, Farkas Z, Aszodi A, Roths J, et al. Early detection of cartilage degeneration: a comparison of histology, fiber bragg grating-based micro-indentation, and atomic force microscopy-based nano-indentation. Int J Mol Sci. 2020;21(19):7384.

Muschter D, Fleischhauer L, Taheri S, Schilling AF, Clausen-Schaumann H, Grässel S. Sensory neuropeptides are required for bone and cartilage homeostasis in a murine destabilization-induced osteoarthritis model. Bone. 2020;133:115181.

Stolz M, Gottardi R, Raiteri R, Miot S, Martin I, Imer R, et al. Early detection of aging cartilage and osteoarthritis in mice and patient samples using atomic force microscopy. Nat Nanotechnol. 2009;4(3):186–92.

Taheri S, Winkler T, Schenk LS, Neuerburg C, Baumbach SF, Zustin J, et al. Developmental transformation and reduction of connective cavities within the subchondral bone. Int J Mol Sci. 2019;20(3):770.

Aicher WK, Rolauffs B. The spatial organisation of joint surface chondrocytes: review of its potential roles in tissue functioning, disease and early, preclinical diagnosis of osteoarthritis. Ann Rheum Dis. 2014;73(4):645–53.

Dexheimer V, Frank S, Richter W. Proliferation as a requirement for in vitro chondrogenesis of human mesenchymal stem cells. Stem Cells Dev. 2012;21(12):2160–9.

Melnik S, Werth N, Boeuf S, Hahn E-M, Gotterbarm T, Anton M, et al. Impact of c-MYC expression on proliferation, differentiation, and risk of neoplastic transformation of human mesenchymal stromal cells. Stem Cell Res Ther. 2019;10(1):73.

Parsch D, Fellenberg J, Brümmendorf TH, Eschlbeck A-M, Richter W. Telomere length and telomerase activity during expansion and differentiation of human mesenchymal stem cells and chondrocytes. J Mol Med Berl Ger. 2004;82(1):49–55.

Pelttari K, Winter A, Steck E, Goetzke K, Hennig T, Ochs BG, et al. Premature induction of hypertrophy during in vitro chondrogenesis of human mesenchymal stem cells correlates with calcification and vascular invasion after ectopic transplantation in SCID mice. Arthritis Rheum. 2006;54(10):3254–66.

Bruckner P, Hörler I, Mendler M, Houze Y, Winterhalter KH, Eich-Bender SG, et al. Induction and prevention of chondrocyte hypertrophy in culture. J Cell Biol. 1989;109(5):2537–45.

Dreier R, Wallace S, Fuchs S, Bruckner P, Grässel S. Paracrine interactions of chondrocytes and macrophages in cartilage degradation: articular chondrocytes provide factors that activate macrophage-derived pro-gelatinase B (pro-MMP-9). J Cell Sci. 2001;114(Pt 21):3813–22.

Blumbach K, Bastiaansen-Jenniskens YM, DeGroot J, Paulsson M, van Osch GJVM, Zaucke F. Combined role of type IX collagen and cartilage oligomeric matrix protein in cartilage matrix assembly: cartilage oligomeric matrix protein counteracts type IX collagen-induced limitation of cartilage collagen fibril growth in mouse chondrocyte cultures. Arthritis Rheum. 2009;60(12):3676–85.

Zaucke F, Dinser R, Maurer P, Paulsson M. Cartilage oligomeric matrix protein (COMP) and collagen IX are sensitive markers for the differentiation state of articular primary chondrocytes. Biochem J. 2001;358(Pt 1):17–24.

Fickert S, Fiedler J, Brenner RE. Identification of subpopulations with characteristics of mesenchymal progenitor cells from human osteoarthritic cartilage using triple staining for cell surface markers. Arthritis Res Ther. 2004;6(5):R422-432.

Joos H, Wildner A, Hogrefe C, Reichel H, Brenner RE. Interleukin-1 beta and tumor necrosis factor alpha inhibit migration activity of chondrogenic progenitor cells from non-fibrillated osteoarthritic cartilage. Arthritis Res Ther. 2013;15(5):R119.

Koelling S, Miosge N. Sex differences of chondrogenic progenitor cells in late stages of osteoarthritis. Arthritis Rheum. 2010;62(4):1077–87.

Madry H, Cucchiarini M, Terwilliger EF, Trippel SB. Recombinant adeno-associated virus vectors efficiently and persistently transduce chondrocytes in normal and osteoarthritic human articular cartilage. Hum Gene Ther. 2003;14(4):393–402.

Cucchiarini M, Thurn T, Weimer A, Kohn D, Terwilliger EF, Madry H. Restoration of the extracellular matrix in human osteoarthritic articular cartilage by overexpression of the transcription factor SOX9. Arthritis Rheum. 2007;56(1):158–67.

Madry H, Cucchiarini M, Kaul G, Kohn D, Terwilliger EF, Trippel SB. Menisci are efficiently transduced by recombinant adeno-associated virus vectors in vitro and in vivo. Am J Sports Med. 2004;32(8):1860–5.

Venkatesan JK, Ekici M, Madry H, Schmitt G, Kohn D, Cucchiarini M. SOX9 gene transfer via safe, stable, replication-defective recombinant adeno-associated virus vectors as a novel, powerful tool to enhance the chondrogenic potential of human mesenchymal stem cells. Stem Cell Res Ther. 2012;3(3):22.

Meng W, Rey-Rico A, Claudel M, Schmitt G, Speicher-Mentges S, Pons F, et al. rAAV-mediated overexpression of SOX9 and TGF-β via carbon dot-guided vector delivery enhances the biological activities in human bone marrow-derived mesenchymal stromal cells. Nanomater Basel Switz. 2020;10(5):855.

Venkatesan JK, Meng W, Rey-Rico A, Schmitt G, Speicher-Mentges S, Falentin-Daudré C, et al. Enhanced chondrogenic differentiation activities in human bone marrow aspirates via sox9 overexpression mediated by pNaSS-grafted PCL film-guided rAAV gene transfer. Pharmaceutics. 2020;12(3):280.

Hartel W. Postgraduate education and role of surgical research in Germany. Surg Today. 1992;22(1):4–9.

Claes L, Recknagel S, Ignatius A. Fracture healing under healthy and inflammatory conditions. Nat Rev Rheumatol. 2012;8(3):133–43.

Rittirsch D, Redl H, Huber-Lang M. Role of complement in multiorgan failure. Clin Dev Immunol. 2012;2012:962927.

Schlundt C, El Khassawna T, Serra A, Dienelt A, Wendler S, Schell H, et al. Macrophages in bone fracture healing: their essential role in endochondral ossification. Bone. 2018;106:78–89.

Tsukamoto T, Chanthaphavong RS, Pape H-C. Current theories on the pathophysiology of multiple organ failure after trauma. Injury. 2010;41(1):21–6.

Frink M, Pape H-C, van Griensven M, Krettek C, Chaudry IH, Hildebrand F. Influence of sex and age on mods and cytokines after multiple injuries. Shock Augusta Ga. 2007;27(2):151–6.

Goodin DS, Aminoff MJ, Chequer RS. Effect of different high-pass filters on the long-latency event-related auditory evoked potentials in normal human subjects and individuals infected with the human immunodeficiency virus. J Clin Neurophysiol Off Publ Am Electroencephalogr Soc. 1992;9(1):97–104.

Fitschen-Oestern S, Lippross S, Klueter T, Weuster M, Varoga D, Tohidnezhad M, et al. A new multiple trauma model of the mouse. BMC Musculoskelet Disord. 2017;18(1):468.

Haffner-Luntzer M, Hankenson KD, Ignatius A, Pfeifer R, Khader BA, Hildebrand F, et al. Review of animal models of comorbidities in fracture-healing research. J Orthop Res Off Publ Orthop Res Soc. 2019;37(12):2491–8.

Histing T, Garcia P, Holstein JH, Klein M, Matthys R, Nuetzi R, et al. Small animal bone healing models: standards, tips, and pitfalls results of a consensus meeting. Bone. 2011;49(4):591–9.

Horst K, Simon TP, Pfeifer R, Teuben M, Almahmoud K, Zhi Q, et al. Characterization of blunt chest trauma in a long-term porcine model of severe multiple trauma. Sci Rep. 2016;21(6):39659.

Peterer L, Ossendorf C, Jensen KO, Osterhoff G, Mica L, Seifert B, et al. Implementation of new standard operating procedures for geriatric trauma patients with multiple injuries: a single level I trauma centre study. BMC Geriatr. 2019;19(1):359.

Taylor SC, Laperriere G, Germain H. Droplet Digital PCR versus qPCR for gene expression analysis with low abundant targets: from variable nonsense to publication quality data. Sci Rep. 2017;7(1):2409.

Metsemakers W-J, Moriarty TF, Nijs S, Pape HC, Richards RG. Influence of implant properties and local delivery systems on the outcome in operative fracture care. Injury. 2016;47(3):595–604.

Augat P, von Rüden C. Evolution of fracture treatment with bone plates. Injury. 2018;49(Suppl 1):S2-7.

Hildebrand F, van Griensven M, Huber-Lang M, Flohe SB, Andruszkow H, Marzi I, et al. Is there an impact of concomitant injuries and timing of fixation of major fractures on fracture healing? A focused review of clinical and experimental evidence. J Orthop Trauma. 2016;30(3):104–12.

Kemmler W, Häberle L, von Stengel S. Effects of exercise on fracture reduction in older adults: a systematic review and meta-analysis. Osteoporos Int J . 2013;24(7):1937–50.

Zwingmann J, Hauschild O, Bode G, Südkamp NP, Schmal H. Malposition and revision rates of different imaging modalities for percutaneous iliosacral screw fixation following pelvic fractures: a systematic review and meta-analysis. Arch Orthop Trauma Surg. 2013;133(9):1257–65.

Hildebrand F, Mommsen P, Frink M, van Griensven M, Krettek C. Genetic predisposition for development of complications in multiple trauma patients. Shock Augusta Ga. 2011;35(5):440–8.

Wafaisade A, Lefering R, Bouillon B, Sakka SG, Thamm OC, Paffrath T, et al. Epidemiology and risk factors of sepsis after multiple trauma: an analysis of 29,829 patients from the Trauma Registry of the German Society for Trauma Surgery. Crit Care Med. 2011;39(4):621–8.

Augat P, Simon U, Liedert A, Claes L. Mechanics and mechano-biology of fracture healing in normal and osteoporotic bone. Osteoporos Int J Establ Result Coop Eur Found Osteoporos Natl Osteoporos Found USA. 2005;16(Suppl 2):S36-43.

Steiner M, Claes L, Ignatius A, Simon U, Wehner T. Numerical simulation of callus healing for optimization of fracture fixation stiffness. PLoS ONE. 2014;9(7):e101370.

Behrendt P, Feldheim M, Preusse-Prange A, Weitkamp JT, Haake M, Eglin D, et al. Chondrogenic potential of IL-10 in mechanically injured cartilage and cellularized collagen ACI grafts. Osteoarthritis Cartilage. 2018;26(2):264–75.

Rolauffs B, Kurz B, Felka T, Rothdiener M, Uynuk-Ool T, Aurich M, et al. Stress-vs-time signals allow the prediction of structurally catastrophic events during fracturing of immature cartilage and predetermine the biomechanical, biochemical, and structural impairment. J Struct Biol. 2013;183(3):501–11.

Guder C, Gravius S, Burger C, Wirtz DC, Schildberg FA. Osteoimmunology: a current update of the interplay between bone and the immune system. Front Immunol. 2020;11:58.

Qazi TH, Duda GN, Ort MJ, Perka C, Geissler S, Winkler T. Cell therapy to improve regeneration of skeletal muscle injuries. J Cachexia Sarcopenia Muscle. 2019;10(3):501–16.

Borgiani E, Figge C, Kruck B, Willie BM, Duda GN, Checa S. Age-related changes in the mechanical regulation of bone healing are explained by altered cellular mechanoresponse. J Bone Miner Res Off J Am Soc Bone Miner Res. 2019;34(10):1923–37.

Hildebrand F, Pape H-C, Horst K, Andruszkow H, Kobbe P, Simon T-P, et al. Impact of age on the clinical outcomes of major trauma. Eur J Trauma Emerg Surg Off Publ Eur Trauma Soc. 2016;42(3):317–32.

Mehta M, Strube P, Peters A, Perka C, Hutmacher D, Fratzl P, et al. Influences of age and mechanical stability on volume, microstructure, and mineralization of the fracture callus during bone healing: is osteoclast activity the key to age-related impaired healing? Bone. 2010;47(2):219–28.

Xu P, Werner J-U, Milerski S, Hamp CM, Kuzenko T, Jähnert M, et al. Diet-induced obesity affects muscle regeneration after murine blunt muscle trauma-a broad spectrum analysis. Front Physiol. 2018;9:674.

Tschaikowsky M, Selig M, Brander S, Balzer BN, Hugel T, Rolauffs B. Proof-of-concept for the detection of early osteoarthritis pathology by clinically applicable endomicroscopy and quantitative AI-supported optical biopsy. Osteoarthritis Cartilage. 2020;19:2282.

Russell WMS, Burch RL. The principles of humane experimental technique. London: Methuen; 1959. https://doi.org/10.5694/j.1326-5377.1960.tb73127.x .

Book   Google Scholar  

Seok J, Warren HS, Cuenca AG, Mindrinos MN, Baker HV, Xu W, et al. Genomic responses in mouse models poorly mimic human inflammatory diseases. Proc Natl Acad Sci U S A. 2013;110(9):3507–12.

Weber B, Lackner I, Haffner-Luntzer M, Palmer A, Pressmar J, Scharffetter-Kochanek K, et al. Modeling trauma in rats: similarities to humans and potential pitfalls to consider. J Transl Med. 2019;17(1):305.

Osuchowski MF, Ayala A, Bahrami S, Bauer M, Boros M, Cavaillon J-M, et al. Minimum quality threshold in pre-clinical sepsis studies (MQTiPSS): an international expert consensus initiative for improvement of animal modeling in sepsis. Intensive Care Med Exp. 2018. https://doi.org/10.1097/SHK.0000000000001212 .

Seichter F, Tütüncü E, Hagemann LT, Vogt J, Wachter U, Gröger M, et al. Online monitoring of carbon dioxide and oxygen in exhaled mouse breath via substrate-integrated hollow waveguide Fourier-transform infrared-luminescence spectroscopy. J Breath Res. 2018;12(3):036018.

Haffner-Luntzer M, Ignatius A. Animal models for studying metaphyseal bone fracture healing. Eur Cell Mater. 2020;29(40):172–88.

Xu B, Chandrasekar A, Olde Heuvel F, Powerski M, Nowak A, Noack L, et al. Ethanol intoxication alleviates the inflammatory response of remote organs to experimental traumatic brain injury. Int J Mol Sci. 2020;21(21):8181.

Hartmann C, Gröger M, Noirhomme J-P, Scheuerle A, Möller P, Wachter U, et al. In-depth characterization of the effects of cigarette smoke exposure on the acute trauma response and hemorrhage in mice. Shock. 2019;51(1):68–77.

Datzmann T, Träger K. Extracorporeal membrane oxygenation and cytokine adsorption. J Thorac Dis. 2018;10(Suppl 5):S653–60.

Oláh T, Michaelis JC, Cai X, Cucchiarini M, Madry H. Comparative anatomy and morphology of the knee in translational models for articular cartilage disorders. Part II: Small animals. Ann Anat Anat Anz Off Organ Anat Ges. 2020;29(234):151630.

Bland-Sutton J. Ligaments; their nature and morphology. British: Lewis; 1897.

Lanzer WL, Komenda G. Changes in articular cartilage after meniscectomy. Clin Orthop. 1990;252:41–8.

Haberkamp S, Oláh T, Orth P, Cucchiarini M, Madry H. Analysis of spatial osteochondral heterogeneity in advanced knee osteoarthritis exposes influence of joint alignment. Sci Transl Med. 2020. https://doi.org/10.1126/scitranslmed.aba9481 .

Verdonk R, Madry H, Shabshin N, Dirisamer F, Peretti GM, Pujol N, et al. The role of meniscal tissue in joint protection in early osteoarthritis. Knee Surg Sports Traumatol Arthrosc Off . 2016;24(6):1763–74.

Wirth CR. Meniscus repair. Clin Orthop. 1981;157:153–60.

Botting J. The History of Thalidomide. Drug News Perspect. 2002;15(9):604–11.

Rai MF, Brophy RH, Sandell LJ. Osteoarthritis following meniscus and ligament injury: insights from translational studies and animal models. Curr Opin Rheumatol. 2019;31(1):70–9.

Lackner I, Weber B, Knecht D, Horst K, Relja B, Gebhard F, et al. Cardiac glucose and fatty acid transport after experimental mono- and polytrauma. Shock. 2020;53(5):620–9.

Hildebrand F, Andruszkow H, Huber-Lang M, Pape H-C, van Griensven M. Combined hemorrhage/trauma models in pigs-current state and future perspectives. Shock Augusta Ga. 2013;40(4):247–73.

Horst K, Simon TP, Pfeifer R, Teuben M, Almahmoud K, Zhi Q, et al. Characterization of blunt chest trauma in a long-term porcine model of severe multiple trauma. Sci Rep. 2016;6:1–3.

Messerer DAC, Vidoni L, Erber M, Stratmann AEP, Bauer JM, Braun CK, et al. Animal-free human whole blood sepsis model to study changes in innate immunity. Front Immunol. 2020;11:571992.

Niemeyer F, Claes L, Ignatius A, Meyers N, Simon U. Simulating lateral distraction osteogenesis. PLoS ONE. 2018;13(3):e0194500.

Wehner T, Claes L, Ignatius A, Simon U. Optimization of intramedullary nailing by numerical simulation of fracture healing. J Orthop Res Off Publ Orthop Res Soc. 2012;30(4):569–73.

Avey MT, Moher D, Sullivan KJ, Fergusson D, Griffin G, Grimshaw JM, et al. The devil is in the details: incomplete reporting in preclinical animal research. PLoS ONE. 2016;11(11):e0166733.

Kilkenny C, Browne WJ, Cuthill IC, Emerson M, Altman DG. Improving bioscience research reporting: the ARRIVE guidelines for reporting animal research. PLOS Biol. 2010;8(6):e1000412.

Reynolds P, Wall P, van Griensven M, McConnell K, Lang C, Buchman T. Shock supports the use of animal research reporting guidelines. Shock. 2012;38(1):1–3.

Denk S, Weckbach S, Eisele P, Braun C, Wiegner R, Ohmann J, et al. Role of hemorrhagic shock in experimental polytrauma. Shock Augusta Ga. 2017;13:49.

Halbgebauer R, Braun CK, Denk S, Mayer B, Cinelli P, Radermacher P, et al. Hemorrhagic shock drives glycocalyx, barrier and organ dysfunction early after polytrauma. J Crit Care. 2018;44:229–37.

Tomaževič M, Kristan A, Kamath AF, Cimerman M. 3D printing of implants for patient-specific acetabular fracture fixation: an experimental study. Eur J Trauma Emerg Surg Off Publ Eur Trauma Soc. 2019. https://doi.org/10.1007/s00068-019-01241-y .

Lai Y, Li Y, Cao H, Long J, Wang X, Li L, et al. Osteogenic magnesium incorporated into PLGA/TCP porous scaffold by 3D printing for repairing challenging bone defect. Biomaterials. 2019;197:207–19.

Beyaz S. A brief history of artificial intelligence and robotic surgery in orthopedics & traumatology and future expectations. Jt Dis Relat Surg. 2020;31(3):653–5.

Huber-Wagner S, Biberthaler P, Häberle S, Wierer M, Dobritz M, Rummeny E, et al. Whole-body CT in haemodynamically unstable severely injured patients—a retrospective, multicentre study. PLoS ONE. 2013;8(7):e68880.

Hussmann B, Lefering R, Waydhas C, Ruchholtz S, Wafaisade A, Kauther MD, et al. Prehospital intubation of the moderately injured patient: a cause of morbidity? A matched-pairs analysis of 1,200 patients from the DGU Trauma Registry. Crit Care Lond Engl. 2011;15(5):R207.

Wafaisade A, Lefering R, Bouillon B, Böhmer AB, Gäßler M, Ruppert M, et al. Prehospital administration of tranexamic acid in trauma patients. Crit Care Lond Engl. 2016;20(1):143.

Rubio I, Osuchowski MF, Shankar-Hari M, Skirecki T, Winkler MS, Lachmann G, et al. Current gaps in sepsis immunology: new opportunities for translational research. Lancet Infect Dis. 2019;19(12):e422–36.

Sas A, Tanck E, Sermon A, van Lenthe GH. Finite element models for fracture prevention in patients with metastatic bone disease. A literature review. . Bone Rep. 2020;12:100286.

Amann E, Amirall A, Franco AR, Poh PSP, Sola Dueñas FJ, Fuentes Estévez G, et al. A graded, porous composite of natural biopolymers and octacalcium phosphate guides osteochondral differentiation of stem cells. Adv Healthc Mater. 2021;10:e2001692.

Goodman SB, Maruyama M. Inflammation Bone Healing and Osteonecrosis: From Bedside to Bench. JIR. 2020;13:913–23.

Busscher HJ, Alt V, van der Mei HC, Fagette PH, Zimmerli W, Moriarty TF, et al. A trans-atlantic perspective on stagnation in clinical translation of antimicrobial strategies for the control of biomaterial-implant-associated infection. ACS Biomater Sci Eng. 2019;5(2):402–6.

A pandemic is no time to cut the European Research Council’s funding. Nature. 2020;585(7825):323–4.

Bucher A. Production des vaccins: quels enseignements tirer de l’expérience COVID ? Vaccine production: what lessons can be learned from the COVID pandemic? Terra Nova. 2021;10.

Schucht P, Roccaro-Waldmeyer DM, Murek M, Zubak I, Goldberg J, Falk S, et al. Exploring novel funding strategies for innovative medical research: the HORAO crowdfunding campaign. J Med Internet Res. 2020;22(11):e19715. https://doi.org/10.2196/19715 .

Ren J, Raghupathi V, Raghupathi W. Understanding the dimensions of medical crowdfunding: a visual analytics approach. J Med Internet Res. 2020;22(7):e18813.

Snyder J, Crooks VA. Is there room for privacy in medical crowdfunding? J Med Ethics. 2020. https://doi.org/10.1136/medethics-2020-106676 .

Kubheka BZ. Bioethics and the use of social media for medical crowdfunding. BMC Med Ethics. 2020;21(1):96.

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We acknowledge Ebru Karasu for helping in finalizing the manuscript.

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Institute of Experimental Orthopaedics and Osteoarthritis Research, Saarland University, Homburg, Germany

Henning Madry

Experimental Orthopedics, Department of Orthopedic Surgery, University of Regensburg, Regensburg, Germany

Susanne Grässel

Department of Orthopaedics and Trauma Surgery, Evangelisches Waldkrankenhaus Berlin Spandau, Berlin, Germany

Ulrich Nöth

Experimental Radiology, University Clinic for Radiology and Nuclear Medicine, Otto-Von-Guericke-University Magdeburg, Magdeburg, Germany

Borna Relja

G.E.R.N. Research Center for Tissue Replacement, Regeneration & Neogenesis, Department of Orthopedics and Trauma Surgery, Medical Center - Albert-Ludwigs-University of Freiburg, Faculty of Medicine, Albert-Ludwigs-University of Freiburg, Breisgau, Germany

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Department of Orthopaedics, Research Lab for Biomechanics and Implant Technology, Rostock University Medical Center, Rostock, Germany

Rainer Bader

Department of Cell Biology-Inspired Tissue Engineering, MERLN-Institute for Technology-Inspired Regenerative Medicine, Maastricht University, Maastricht, The Netherlands

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Department of Orthopaedics and Trauma Surgery, University Hopsital Bonn, Bonn, Germany

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Madry, H., Grässel, S., Nöth, U. et al. The future of basic science in orthopaedics and traumatology: Cassandra or Prometheus?. Eur J Med Res 26 , 56 (2021). https://doi.org/10.1186/s40001-021-00521-x

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Received : 08 February 2021

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DOI : https://doi.org/10.1186/s40001-021-00521-x

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