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Abstract Background The primary aim of this study was to quantitatively analysis the acetabular morphological feature and 2D/3D coverage of the Crowe IV DDH hip, dividing into subgroups by the false acetabulum. The secondary aim was to propose a 3D bone mapping to determine acetabular bone defect analysis from the perspective of the implanted simulation. Methods A total of 53 Crowe IV hips (27 hips without the false acetabulum in IVa group and 26 hips in IVb group) and 40 normal hips met the inclusion criteria and were retrospectively evaluated. Firstly, the anatomical size and volume of the acetabulum were measured quantitatively. Secondly, through the simulated implantation, morphological assessments of the true acetabulum included Cup-CE, Cup-Sharp, acetabular anteversion angle, and thickness of the medial wall. Last, Acetabular sector angles (ASAs) and the component coverage ratio were measured to provide coverage indices. Further, 3D bone mapping visualization was applied to determine the uncovered component portion distribution. Results The anatomic shape and volume of the acetabular triangle were significantly smaller in Crowe IV hips. At the level of the acetabular component center, IVb acetabula were found to be more anteverted and abductive, with smaller Cup-CE and larger Cup-Sharp angles. The coverage sector angles in Crowe IVa hips were larger in the anterosuperior and superior direction, while smaller in the posterosuperior and posterior direction, with no subgroup difference in total component coverage. Both 3D bone mapping and correlation analysis reveal that posterosuperior and posterior bone stock is highly associated with the component coverage. Conclusion With the presence of the false acetabulum, there existed acetabular anteversion and segmental coverage distinctions between subgroups. During the acetabular reconstruction, management of posterosuperior and posterior bone stock was important for ideal component coverage.

Human umbilical cord mesenchymal stem cells (UCMSCs) are a novel stem-cell source to treat osteoarthritis (OA). Here we investigated the therapeutic effects of UCMSCs injection strategies on knee OA in a rabbit model. Thirty OA rabbits randomly received normal saline, a single dose of 1 × 106 UCMSCs, or three injections of 1 × 106 UCMSCs at 2, 4, 6 weeks. Articular cartilages were collected after 8 weeks. Macroscopic and histological assessments indicated that intra-articular injection of UCMSCs, both single and multiple injection, significantly reduced the formation of periarticular osteophytes and articular cartilage degeneration when compared with the control. Furthermore, both UCMSCs injections increased the expression of chondrogenic markers in the articular cartilage, and reduced the levels of TNF-α and IL-6 in synovium. Micro-CT showed significant reduction of sub-chondral bone degeneration and osteophytes in the multiple-injection group compared to the control and single-injection group. Taken together, intra-articular injection of UCMSCs for OA treatment is safe and effective. Single and multiple injection of UCMSCs had comparable reparative effect on cartilage lesions, while multiple injection of UCMSCs further exerted effect on enhancing subchondral bone volume.

Abstract Tendinopathy is one of the most common musculoskeletal diseases, and mechanical overload is considered its primary cause. However, the underlying mechanism through which mechanical overload induces tendinopathy has not been determined. In this study, we identified for the first time that tendon cells can release extracellular mitochondria (ExtraMito) particles, a subtype of medium extracellular particles (mEPs), into the environment through a process regulated by mechanical loading. RNA sequencing systematically revealed that oxygen-related reactions, extracellular particles, and inflammation were present in diseased human tendons, suggesting that these factors play a role in the pathogenesis of tendinopathy. We simulated the disease condition by imposing a 9% strain overload on three-dimensional mouse tendon constructs in our cyclic uniaxial stretching bioreactor. The three-dimensional mouse tendon constructs under normal loading with 6% strain exhibited an extended mitochondrial network, as observed through live-cell confocal laser scanning microscopy. In contrast, mechanical overload led to a fragmented mitochondrial network. Our microscopic and immunoblot results demonstrated that mechanical loading induced tendon cells to release ExtraMito particles. Furthermore, we showed that mEPs released from tendon cells overloaded with a 9% strain (mEP9%) induced macrophage chemotaxis and increased the production of proinflammatory cytokines, including IL-6, CXCL1, and IL-18, from macrophages compared to mEP0%, mEP3%, and mEP6%. Partial depletion of the ExtraMito particles from mEP9% by magnetic-activated cell sorting significantly reduced macrophage chemotaxis. N-acetyl-L-cysteine treatment preserved the mitochondrial network in overloaded tendon cells, diminishing overload-induced macrophage chemotaxis toward mEP9%. These findings revealed a novel mechanism of tendinopathy; in an overloaded environment, ExtraMito particles convey mechanical response signals from tendon cells to the immune microenvironment, culminating in tendinopathy.

Background Glucocorticoids have been widely used in perioperative period for postoperative pain relief after total knee arthroplasty (TKA). However, the optimal administration protocols of glucocorticoids remain controversial. This study aims to compare the efficacy of glucocorticoids between intravenous and periarticular injection on clinical outcomes. Methods A total of 114 patients were randomly assigned to intravenous (IV) group ( n = 57) and periarticular injection (PI) group ( n = 57). The IV group received 10 mg dexamethasone intravenously and the PI group received periarticular injection of 10 mg dexamethasone during the procedure. The clinical outcomes were assessed using visual analogue scale (VAS), knee society score (KSS), range of motion (ROM), knee swelling, inflammation markers and complications after TKA. Results The VAS score during walking at 2nd day postoperatively was lower in the PI group compared with the IV group (2.08 ± 1.45 vs 2.73 ± 1.69, p = .039), and there was no significant difference at the other time points of VAS score in two groups. The inflammation markers, knee swelling, knee ROM and KSS score were not statistically different. Vomiting and other complications occurrence were not significantly different between the two groups. Conclusions Intraoperative periarticular injection of glucocorticoids has similar analgesic effect compared to intravenous in the postoperative period following TKA and may be even more effective on the second postoperative day. In addition, periarticular injection of glucocorticoids does not impose an excess risk or complication on patients.

Abstract Introduction Accumulated clinical trials had been focused on stem cell therapy in combination of core decompression (CD) in the treatment of avascular necrosis of the femoral head (ANFH). Nonetheless, the results were inconclusive. Here, we performed a systematic review and meta-analysis of previous randomized controlled trials (RCTs) and retrospective studies to assess whether combined stem cell augmentation with CD improved the outcomes of ANFH compared with CD alone. Methods The current study included 11 RCTs and 7 retrospective studies reporting the clinical outcomes of a total of 916 patients and 1257 hips. 557 and 700 hips received CD and CD plus stem cell therapy, respectively. To compare CD with CD plus stem cell therapy, we examined the clinical evaluating scores, the occurrence of the femoral head, radiologic progression and conversion to total hip arthroplasty (THA). Results Only 10 studies reported significantly greater improvement in hip functions while combining stem cell procedure with CD. The pooled results in subgroup analysis indicated that stem cell group had a lower collapse rate on a mid-term basis (P = 0.001), when combined with mechanical support (P

After spinal cord injury (SCI), endogenous neural stem cells are activated and migrate to the injury site where they differentiate into astrocytes, but they rarely differentiate into neurons. It is difficult for brain-derived information to be transmitted through the injury site after SCI because of the lack of neurons that can relay neural information through the injury site, and the functional recovery of adult mammals is difficult to achieve. The development of bioactive materials, tissue engineering, stem cell therapy, and physiotherapy has provided new strategies for the treatment of SCI and shown broad application prospects, such as promoting endogenous neurogenesis after SCI. In this review, we focus on novel approaches including tissue engineering, stem cell technology, and physiotherapy to promote endogenous neurogenesis and their therapeutic effects on SCI. Moreover, we explore the mechanisms and challenges of endogenous neurogenesis for the repair of SCI.

Joint arthroplasty is an option for end-stage septic arthritis due to joint infection after effective control of infection. However, complications such as osteolysis and aseptic loosening can arise afterwards due to wear and tear caused by high joint activity after surgery, necessitating joint revision. Some studies on tissue pathology after prosthesis implantation have identified various cell populations involved in the process. However, these studies have often overlooked the complexity of the altered periprosthetic microenvironment, especially the role of nano wear particles in the etiology of osteolysis and aseptic loosening. To address this gap, we propose the concept of the “prosthetic microenvironment”. In this perspective, we first summarize the histological changes in the periprosthetic tissue from prosthetic implantation to aseptic loosening, then analyze the cellular components in the periprosthetic microenvironment post prosthetic implantation. We further elucidate the interactions among cells within periprosthetic tissues, and display the impact of wear particles on the disturbed periprosthetic microenvironments. Moreover, we explore the origins of disease states arising from imbalances in the homeostasis of the periprosthetic microenvironment. The aim of this review is to summarize the role of relevant factors in the microenvironment of the periprosthetic tissues, in an attempt to contribute to the development of innovative treatments to manage this common complication of joint replacement surgery.

Abstract Tendon is composed of dense fibrous connective tissues, connecting muscle at the myotendinous junction (MTJ) to bone at the enthesis and allowing mechanical force to transmit from muscle to bone. Tendon diseases occur at different zones of the tendon, including enthesis, MTJ and midsubstance of the tendon, due to a variety of environmental and genetic factors which consequently result in different frequencies and recovery rates. Self-healing properties of tendons are limited, and cell therapeutic approaches in which injured tendon tissues are renewed by cell replenishment are highly sought after. Homologous use of individual’s tendon-derived cells, predominantly differentiated tenocytes and tendon-derived stem cells, is emerging as a treatment for tendinopathy through achieving minimal cell manipulation for clinical use. This is the first review summarizing the progress of tendon-derived cell therapy in clinical use and its challenges due to the structural complexity of tendons, heterogeneous composition of extracellular cell matrix and cells and unsuitable cell sources. Further to that, novel future perspectives to improve therapeutic effect in tendon-derived cell therapy based on current basic knowledge are discussed.

Abstract Severe peripheral nerve injury leads to the irreparable disruption of nerve fibers. This leads to disruption of synapses with the designated muscle, which consequently go through progressive atrophy and damage of muscle function. The molecular mechanism that underlies the re-innervation process has yet to be evaluated using proteomics or transcriptomics. In the present study, multi-dimensional data were therefore integrated with transcriptome and proteome profiles in order to investigate the mechanism of re-innervation in muscles. Two simulated nerve injury muscle models in the rat tibial nerve were compared: the nerve was either cut (denervated, DN group) or crushed but with the nerve sheath intact (re-innervated, RN group). The control group had a preserved and intact tibial nerve. At 4 weeks, the RN group showed better tibial nerve function and recovery of muscle atrophy compared to the DN group. As the high expression of Myh3, Postn, Col6a1 and Cfi, the RN group demonstrated superior re-innervation as well. Both differentially expressed genes (DEGs) and proteins (DEPs) were enriched in the peroxisome proliferator-activated receptors (PPARs) signaling pathway, as well as the energy metabolism. This study provides basic information regarding DEGs and DEPs during re-innervation-induced muscle atrophy. Furthermore, the crucial genes and proteins can be detected as possible treatment targets in the future.

Background: Degenerative diseases in orthopaedics have become a significant global public health issue with the aging of the population worldwide. The traditional medical interventions, including physical therapy, pharmacological therapy and even surgery, hardly work to modify degenerative progression. Stem cell–based therapy is widely accepted to treat degenerative orthopaedic disease effectively but possesses several limitations, such as the need for strict monitoring of production and storage and the potential risks of tumorigenicity and immune rejection in clinical translation. Furthermore, the ethical issues surrounding the acquisition of embryonic stem cells are also broadly concerned. Exosome-based therapy has rapidly grown in popularity in recent years and is regarded as an ideal alternative to stem cell–based therapy, offering a promise to achieve ‘cell-free’ tissue regeneration. Methods: Traditionally, the native exosomes extracted from stem cells are directly injected into the injured site to promote tissue regeneration. Recently, several modified exosome–based strategies were developed to overcome the limitations of native exosomes, which include mainly exogenous molecule loading and exosome delivery through scaffolds. In this paper, a systematic review of the exosome-based strategy for degenerative disease in orthopaedics is presented. Results: Treatment strategies based on the native exosomes are effective but with several disadvantages such as rapid diffusion and insufficient and fluctuating functional contents. The modified exosome–based strategies can better match the requirements of the regeneration in some complex healing processes. Conclusion: Exosome-based strategies hold promise to manage degenerative disease in orthopaedics prior to patients reaching the advanced stage of disease in the future. The timely summary and highlights offered herein could provide a research perspective to promote the development of exosome-based therapy, facilitating the clinical translation of exosomes in orthopaedics. Translational potential of this article: Exosome-based therapy is superior in anti-senescence and anti-inflammatory effects and possesses lower risks of tumorigenicity and immune rejection relative to stem cell–based therapy. Exosome-based therapy is regarded as an ideal alternative to stem cell–based therapy, offering a promise to achieve ‘cell-free’ tissue regeneration.

Abstract Purpose To determine the repair of LMPR lesions would improve the ACL graft maturation. Method A total of 49 patients underwent ACL reconstruction were included in this study. Patients were furtherly sub-grouped according to the status of LMPR: intact (17), repair (16) and resected (16). Assessments performed pre- and 2 years post-operatively included patients-reported scores and arthrometer side-to-side difference. Magnetic resonance imaging was used 2 years after the surgery to compare the lateral meniscal extrusion (LME), anterior tibial subluxation of the medial compartment (ATSMC), anterior tibial subluxation of the lateral compartment (ATSLC), the difference of ATSMC and ATSLC, and signal/noise quotient (SNQ) of ACL graft. Results In LMPR resected group, it showed greater post-operative ATSMC-ATSLC difference when compared with pre-operatively (P = 0.006) and with the other 2 groups (intact: P = 0.031; repair: P = 0.048). SNQ of ACL graft was higher in LMPR resected group than those in LMPR intact (P = 0.004) and repair group (P = 0.002). The LMPR repair group showed significant reduction in LME post-operatively (P = 0.001). Post-operative measures on ATSLC-ATSMC difference (β = 0.304, P = 0.049) and LME (β = 0.492, P = 0.003) showed significant association with graft SNQ. Conclusions Transtibial repair of LMPR concomitant with ACL reconstruction restored translational stability, reduced meniscus extrusion, making it beneficial for ACL graft maturation.

Abstract Background Femur-tibia angle (FTA) and patella-tibia angle (PTA) are two MRI measurements that reflect the rotation of the knee joint. The purposes of this study were to assess whether FTA and PTA are associated with ACL tear and to explore their roles in ACL tear diagnosis. Methods FTA, PTA, ACL angle and anterior tibial subluxation were compared between the two matched groups: ACL tear group and control group (each n = 20). Diagnostic performance was evaluated in a consecutive 120-patient cohort who underwent MR imaging of the knee and subsequently had arthroscopy. Different measurements were assessed by area under the curve (AUC) of receiver operating characteristic (ROC) curve. Results FTA and PTA increased significantly in ACL tears group when compared to the control group (4.79 and 7.36 degrees, respectively, p

Abstract Background When performing femoral reconstruction in patients with Crowe type IV developmental dysplasia of the hip (DDH), anatomical deformity presents many technical challenges to orthopedic surgeons. The false acetabulum is suggested to influence load transmission and femoral development. The aim of this study was to describe the morphological features of dysplastic femurs in Crowe type IV DDH and further evaluate the potential effect of the false acetabulum on morphological features and medullary canal of Crowe type IV femurs. Methods We analyzed preoperative computed tomography scans from 45 patients with 51 hips (25 hips without false acetabulum in the IVa group and 26 hips with false acetabulum in the IVb group) who were diagnosed with Crowe type IV DDH and 30 normal hips in our hospital between January 2009 and January 2019. Three-dimensional reconstruction was performed using Mimics software, and the coronal femoral plane was determined to evaluate the following parameters: dislocation height, dislocation ratio, height of the femoral head (FH), height of the greater trochanter (GT), GT–FH height discrepancy, height of the isthmus, neck-shaft angle, femoral offset and anteversion of the femoral neck. The mediolateral (ML) width, anterolateral (AP) width and diameter of medullary canal of the proximal femur were measured on the axial sections. Further, canal flare index (CFI), metaphyseal-CFI and diaphyseal-CFI were also calculated. Results Compared with the normal femurs, the Crowe type IV DDH femurs had a higher femoral head, larger GT–FH height discrepancy, larger femoral neck anteversion, higher isthmus position and smaller femoral offset. Dislocation height and dislocation rate were significantly larger in the IVa DDH group (65.34 ± 9.83 mm vs. 52.24 ± 11.42 mm). Further, the IVb femurs had a significantly lower isthmus position, larger neck-shaft angle and smaller femoral neck anteversion than IVa femurs. The ML, AP canal widths and the diameter of medullary canal in both DDH groups were significantly smaller than the normal group. Dimensional parameters of IVa femurs were also narrower than IVb femurs in most sections, but with no difference at the level of isthmus. According to the CFIs, the variation of proximal medullary canal in IVb femurs was mainly located in the diaphyseal region, while that in IVa femurs was located in the whole proximal femur. Conclusions High dislocated femurs are associated with more anteverted femoral neck, smaller femoral offset and narrower medullary canal. Without stimulation of the false acetabulum, IVa DDH femurs were associated with higher dislocation and notably narrower medullary canal, whose variation of medullary canal was located in the whole proximal femur.

ObjectivesSpinal cord injury (SCI) remodels the brain structure and alters brain function. To identify specific changes in brain gray matter volume (GMV) and white matter volume (WMV) following SCI, we conducted a voxel-based meta-analysis of whole-brain voxel-based morphometry (VBM) studies.MethodsWe performed a comprehensive literature search on VBM studies that compared SCI patients and healthy controls in PubMed, Web of Science and the China National Knowledge Infrastructure from 1980 to April 2022. Then, we conducted a voxel-based meta-analysis using seed-based d mapping with permutation of subject images (SDM-PSI). Meta-regression analysis was performed to identify the effects of clinical characteristics.ResultsOur study collected 20 studies with 22 GMV datasets and 15 WMV datasets, including 410 patients and 406 healthy controls. Compared with healthy controls, SCI patients showed significant GMV loss in the left insula and bilateral thalamus and significant WMV loss in the bilateral corticospinal tract (CST). Additionally, a higher motor score and pinprick score were positively related to greater GMV in the right postcentral gyrus, whereas a positive relationship was observed between the light touch score and the bilateral postcentral gyrus.ConclusionAtrophy in the thalamus and bilateral CST suggest that SCI may trigger neurodegeneration changes in the sensory and motor pathways. Furthermore, atrophy of the left insula may indicate depression and neuropathic pain in SCI patients. These indicators of structural abnormalities could serve as neuroimaging biomarkers for evaluating the prognosis and treatment effect, as well as for monitoring disease progression. The application of neuroimaging biomarkers in the brain for SCI may also lead to personalized treatment strategies.Systematic review registrationhttps://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42021279716, identifier: CRD42021279716.

Background: Tendons are the force transferring tissue that enable joint movement. Excessive mechanical loading is commonly considered as a primary factor causing tendinopathy, however, an increasing body of evidence supports the hypothesis that overloading creates microdamage of collagen fibers resulting in a localized decreased loading on the cell population within the damaged site. Heterotopic ossification is a complication of late stage tendinopathy, which can significantly affect the mechanical properties and homeostasis of the tendon. Here, we the examine the effect of mechanical underloading on tendon ossification and investigate its underlying molecular mechanism. Method: Rabbit Achilles tendons were dissected and cultured in an underloading environment (3% cyclic tensile stain,0.25 ​Hz, 8 ​h/day) for either 10, 15 or 20 days. Using isolated tendon-derived stem cells (TDSCs) 3D constructs were generated, cultured and subjected to an underloading environment for 6 days. Histological assessments were performed to evaluate the structure of the 3D constructs; qPCR and immunohistochemistry were employed to study TDSC differentiation and the β-catenin signal pathway was investigated by Western blotting. Mechanical testing was used to determine ability of the tendon to withstand force generation. Result: Tendons cultured for extended times in an environment of underloading showed progressive heterotopic ossification and a reduction in biomechanical strength. qPCR revealed that 3D TDSCs constructs cultured in an underloading environment exhibited increased expression of several osteogenic genes: these include RUNX2, ALP and osteocalcin in comparison to tenogenic differentiation markers (scleraxis and tenomodulin). Immunohistochemical analysis further confirmed high osteocalcin production in 3D TDSCs constructs subject to underloading. Western blotting of TDSC constructs revealed that β-catenin accumulation and translocation were associated with an increase in phosphorylation at Ser552 and decrease phosphorylation at Ser33. Conclusion: These findings unveil a potential mechanism for heterotopic ossification in tendinopathy due to the underloading of TDSCs at the damage sites, and also that β-catenin could be a potential target for treating heterotopic ossification in tendons. The Translational potential: Tendon heterotopic ossification detrimentally affect quality of life especially for those who has atheletic career. This study reveals the possible mechanism of heterotpic ossification in tendon related to mechanical loading. This study provided the possible to develop a mechanical stimulation protocol for preventive and therapeutic purpose for tendon heterotopic ossification.

Abstract Background Femoral neck fractures in elderly patients typically warrant operative treatment and are related to high risks of mortality and morbidity. As early hip arthroplasties for elderly femoral neck fractures are widely accepted, rapid predicting models that allowed quantitative and individualized prognosis assessments are strongly needed as references for orthopedic surgeons during preoperative conversations. Methods Data of patients aged ≥ 65 years old who underwent primary unilateral hemiarthroplasty or total hip arthroplasty due to femoral neck fracture between January 1st, 2012 and June 30th, 2019 in our center were collected. Candidate variables included demographic data, comorbidities, and routine preoperative screening tests. The main outcomes included 1-year mortality and free walking rate after hip arthroplasty. Patients were randomly divided into derivation and validation groups in the ratio of three to one. Nomograms were developed based on multivariable logistic regressions of derivation group via R language. One thousand bootstraps were used for internal validation. Those models were further tested in the validation group for external validation. Results The final analysis was performed on 702 patients after exclusion and follow-up. All-cause 1-year mortality of the entire data set was 23.4%, while the free walking rate was 57.3%. Preoperative walking ability showed the biggest impact on predicting 1-year mortality and walking ability. Static nomograms were created from the final multivariable models, which allowed simplified graphical computations for the risks of 1-year mortality and walking ability in a certain patient. The bias-corrected C index of those nomograms for predicting 1-year mortality in the derivation group and the validation group were 0.789 and 0.768, while they were 0.807 and 0.759 for predicting postoperative walking ability. The AUC of the mortality and walking ability predicting models were 0.791 and 0.818, respectively. Conclusions Our models enabled rapid preoperative 1-year mortality and walking ability predictions in Asian elderly femoral neck fracture patients who planned for hip arthroplasty, with adequate predictive discrimination and calibration. Those rapid assessment models could help surgeons in making more reasonable clinical decisions and subsequently reducing the risk of potential medical dispute via quantitative and individualized prognosis assessments.

Abstract Background Treatment of avascular necrosis of the femoral head (ANFH) in young patients remains a clinical challenge. A current controversy is whether hip-preserving surgery results in better outcomes. The adverse effects of hip-preserving surgery are associated with the fill material for the necrotic areas. This study aims to evaluate the early effects of autologous bone marrow buffy coat (BBC) and angioconductive bioceramic rod (ABR) grafting with advanced core decompression (ACD) on early ANFH. Methods Forty-four (57 hips) patients with early ANFH from 2015 to 2020 were recruited for this study. They were randomized into two groups: group A received ACD, BBC, and ABR grafting; group B received treatment of ACD with β-tricalcium phosphate (β-TCP) granules and ABR grafting. The outcomes were assessed using the Harris Hip Scores (HHS) and survival rate analysis. The follow-up endpoint was defined as conversion to total hip arthroplasty (THA). Results Forty patients (51 hips) were ultimately included in this study for analysis. Compared with group B, patients in group A had higher postoperative function score (P = 0.032) and postoperative Harris Hip Scores (HHS) (P = 0.041). Kaplan-Meier analysis showed a trend that the survivorship of the femoral head was higher in group A than in group B. Conclusion The short-term follow-up results showed that the autologous bone marrow buffy coat and angioconductive bioceramic rod grafting with advanced core decompression is effective in the treatment of early ANFH. Trial registration Chictr.org.cn , ChiCTR2000039595. Retrospectively registered on 11 February 2015.

This preliminary research determines whether a combination of reverse end-to-side neurorrhaphy and rapamycin treatment achieves a better functional outcome than a single application after prolonged peripheral nerve injury. We found that the tibial nerve function of the reverse end-to-side + rapamycin group recovered better, with a higher tibial function index value, higher amplitude recovery rate, and shorter latency delay rate (P < 0.05). The reverse end-to-side + rapamycin group better protected the gastrocnemius muscle with more forceful contractility, tetanic tension, and a higher myofibril cross-sectional area (P < 0.05). Combining reverse end-to-side neurorrhaphy with rapamycin treatment is a practical approach to promoting the recovery of chronically denervated muscle atrophy after peripheral nerve injury.

Abstract Background Botulinum toxin (Botox) injection is in widespread clinical use for the treatment of muscle spasms and tendinopathy but the mechanism of action is poorly understood. Hypothesis We hypothesised that the reduction of patellar-tendon mechanical-loading following intra-muscular injection of Botox results in tendon atrophy that is at least in part mediated by the induction of senescence of tendon-derived stem cells (TDSCs). Study design Controlled laboratory study Methods A total of 36 mice were randomly divided into 2 groups (18 Botox-injected and 18 vehicle-only control). Mice were injected into the right vastus lateralis of quadriceps muscles either with Botox (to induce mechanical stress deprivation of the patellar tendon) or with normal saline as a control. At 2 weeks post-injection, animals were euthanized prior to tissues being harvested for either evaluation of tendon morphology or in vitro studies. TDSCs were isolated by cell-sorting prior to determination of viability, differentiation capacity or the presence of senescence markers, as well as assessing their response to mechanical loading in a bioreactor. Finally, to examine the mechanism of tendon atrophy in vitro, the PTEN/AKT-mediated cell senescence pathway was evaluated in TDSCs from both groups. Results Two weeks after Botox injection, patellar tendons displayed several atrophic features including tissue volume reduction, collagen fibre misalignment and increased degradation. A colony formation assay revealed a significantly reduced number of colony forming units of TDSCs in the Botox-injected group compared to controls. Multipotent differentiation capacities of TDSCs were also diminished after Botox injection. To examine if mechanically deprived TDSC are capable of forming tendon tissue, we used an isolated bioreactor system to culture tendon constructs using TDSC. These results showed that TDSCs from the Botox-treated group failed to restore tenogenic differentiation after appropriate mechanical loading. Examination of the signalling pathway revealed that injection of Botox into quadriceps muscles causes PTEN/AKT-mediated cell senescence of TDSCs. Conclusion Intramuscular injection of Botox interferes with tendon homeostasis by inducing tendon atrophy and senescence of TDSCs. Botox injection may have long-term adverse consequences for the treatment of tendinopathy. Clinical relevance Intramuscular Botox injection for tendinopathy or tendon injury could result in adverse effects in human tendons and evaluation of its long-term efficacy is warranted.

Abstract Background Although medical intervention of periprosthetic bone loss in the immediate postoperative period was recommended, not all the patients experienced periprosthetic bone loss after total hip arthroplasty (THA). Prediction tools that enrolled all potential risk factors to calculate an individualized prediction of postoperative periprosthetic bone loss were strongly needed for clinical decision-making. Methods Data of the patients who underwent primary unilateral cementless THA between April 2015 and October 2017 in our center were retrospectively collected. Candidate variables included demographic data and bone mineral density (BMD) in spine, hip, and periprosthetic regions that measured 1 week after THA. Outcomes of interest included the risk of postoperative periprosthetic bone loss in Gruen zone 1, 7, and total zones in the 1st postoperative year. Nomograms were presented based on multiple logistic regressions via R language. One thousand Bootstraps were used for internal validation. Results Five hundred sixty-three patients met the inclusion criteria were enrolled, and the final analysis was performed in 427 patients (195 male and 232 female) after the exclusion. The mean BMD of Gruen zone 1, 7, and total were decreased by 4.1%, 6.4%, and 1.7% at the 1st year after THA, respectively. 61.1% of the patients (261/427) experienced bone loss in Gruen zone 1 at the 1st postoperative year, while there were 58.1% (248/427) in Gruen zone 7 and 63.0% (269/427) in Gruen zone total. Bias-corrected C-index for risk of postoperative bone loss in Gruen zone 1, 7, and total zones in the 1st postoperative year were 0.700, 0.785, and 0.696, respectively. The most highly influential factors for the postoperative periprosthetic bone loss were primary diagnosis and BMD in the corresponding Gruen zones at the baseline. Conclusions To the best of our knowledge, our study represented the first time to use the nomograms in estimating the risk of postoperative periprosthetic bone loss with adequate predictive discrimination and calibration. Those predictive models would help surgeons to identify high-risk patients who may benefit from anti-bone-resorptive treatment in the early postoperative period effectively. It is also beneficial for patients, as they can choose the treatment options based on a reasonable expectation following surgery.

Objectives: Residual hip dysplasia is the most common underlying condition leading to secondary osteoarthritis (OA) of the hip. Subchondral bone alterations in OA secondary to hip dysplasia (HD-OA) are poorly investigated. The aim of the present study was to analyse the microarchitecture, bone remodelling and pathological alterations of subchondral bone in femoral heads from patients with HD-OA. Methods: Subchondral bone specimens were extracted from both weight-bearing and non–weight-bearing regions of femoral heads from 20 patients with HD-OA and 20 patients with osteoporotic femoral neck fracture, during hip replacement surgery. Micro-CT and histological examination were performed to assess the microarchitecture and histopathological changes. Results: The weight-bearing subchondral bone showed significantly more sclerotic microarchitecture and higher bone remodelling level in HD-OA as compared with osteoporosis. In the non–weight-bearing region, the two diseases shared similar microarchitectural characteristics, but higher bone remodelling level was detected in HD-OA. Distinct regional differences were observed in HD-OA, whereas the two regions exhibited similar characteristics in osteoporosis. In addition, HD-OA displayed more serious pathological alterations, including subchondral bone cyst, metaplastic cartilaginous tissue, bone marrow oedema and fibrous tissue, especially in the weight-bearing region. Conclusions: Osteoarthritic deteriorations of subchondral bone induced by hip dysplasia spread throughout the whole joint, but exhibit region-dependent variations, with the weight-bearing region more seriously affected. Biomechanical stress might exert a pivotal impact on subchondral bone homeostasis in hip dysplasia. The translational potential of this article: The histomorphometric findings in the project indicate an early intervention for the development of hip dysplasia in clinic.

Abstract Background A method that can accurately predict the outcome of surgery can give patients timely feedback. In addition, to some extent, an objective evaluation method can help the surgeon quickly summarize the patient’s surgical experience and lessen dependence on the long wait for follow-up results. However, there was still no precise tool to predict clinical outcomes of total knee arthroplasty (TKA). This study aimed to develop a scoring system to predict clinical results of TKA and then grade the quality of TKA. Methods We retrospectively reviewed 98 primary TKAs performed between April 2013 and March 2017 to determine predictors of clinical outcomes among lower-extremity angles of alignment. Applying multivariable linear-regression analysis, we built Models (i) and (ii) to predict detailed clinical outcomes which were evaluated using the Knee Society Score (KSS). Multivariable logistic-regression analysis was used to establish Model (iii) to predict probability of getting a good clinical outcome (PGGCO) which was evaluated by Knee Injury and Osteoarthritis Outcome Score (KOOS) score. Finally, we designed a new scoring system consisting of 3 prediction models and presented a method of grading TKA quality. Thirty primary TKAs between April and December 2017 were enrolled for external validation. Results We set up a scoring system consisting of 3 models. The interpretations of Model (i) and (ii) were good (R2 = 0.756 and 0.764, respectively). Model (iii) displayed good discrimination, with an area under the curve (AUC) of 0.936, and good calibration according to the calibration curve. Quality of surgery was stratified as follows: “A” = PGGCO ≥0.8, “B” = PGGCO ≤0.6 but

Abstract Background Avascular necrosis of the femoral head (ANFH) is a severely disabling disease of the hip. Several clinical trials have shown promising outcomes on the use of mesenchymal stem cells for the treatment of ANFH, but long-term clinical assessments are lacking. Previously, we reported the 2-year follow-up results of a prospective, double-blinded, randomized, controlled study on autologous bone marrow buffy coat grafting combined with core decompression in patients with ANFH. Here, we report the 10-year follow-up results of this study. Methods We recruited 43 (53 hips) patients from 2009 to 2010. The hips were randomly allocated to code decompression (CD) with or without bone marrow buffy coat (BBC) grafting. Participants underwent follow-up at 24, 60, and 120 months postoperatively. The visual analogue scale (VAS), Lequesne algofunctional index, and Western Ontario and McMaster Universities Arthritis Index (WOMAC) osteoarthritis scores were recorded. Survival rate analysis and prognostic factor analysis were performed. The endpoint was defined as progression to Ficat stage IV or conversion to hip arthroplasty. Results A total of 31 patients (41 hips) were included in the final analysis. The CD + BBC group had better subjective assessment scores than the CD group. The average survival times were 102.3 months and 78.1 months in the CD + BBC group and CD group, respectively (log-rank test, P = 0.029). In the univariate Cox proportional hazards regression model, age [hazard ratio (HR) = 1.079, P = 0.047] and preoperative Ficat stage (HR = 3.283, P = 0.028) indicated a high risk for progression, while the use of BBC (HR = 0.332, P = 0.042) indicated a low risk. Preoperative Ficat stage III was isolated as an independent risk factor for clinical failure in the multivariate model (HR = 3.743, P = 0.018). Conclusion The 10-year follow-up results of this prospective, double-blinded, randomized, controlled study showed that the use of autologous BBC in combination with core decompression was more effective than the use of core decompression alone. Trial registration ClinicalTrials.gov, NCT01613612 . Registered on 13 December 2011—retrospectively registered

Abstract Background Design modifications in prostheses may cause alterations in gait kinematics, thus influencing functional restoration of knees after total knee arthroplasty (TKA). The aim of the study was to investigate the differences in gait kinematics and clinical outcomes after single radius (SR) versus multiple radius (MR) TKA. Method The present retrospective study included 38 unilateral TKA involving 20 knees using MR design implant and 18 knees using SR design implant. Thirty-six healthy volunteers were also recruited. The mean follow-up time was 16 ± 3 months. At the end of follow-up, the 6 degrees of freedom (DOF) kinematics of knees and range of motion (ROM) were measured with a portable optical tracking system. Knee society score (KSS) and knee injury, and osteoarthritis outcome score (KOOS) were also collected. Results Patients in the SR group had significantly higher scores in activities of daily living (84.7 ± 15.9) and sports and recreation (67.5 ± 25.2) KOOS sub-score than MR group (69.9 ± 17.6, P = 0.012; 50.0 ± 20.8, P = 0.027, respectively). Significant differences were detected between MR knees and SR knees (1.82° ± 3.11° vs 4.93° ± 3.58°, P = 0.009), and MR knees and healthy knees (1.82° ± 3.11° vs 3.62° ± 3.52°, P = 0.032) in adduction/abduction ROM. The proximal/distal translation was significantly smaller in MR knees (0.58 ± 0.54 cm) compared with SR knees (1.03 ± 0.53 cm, P = 0.003) or healthy knees (0.84 ± 0.45 cm, P = 0.039). SR knees (0.24 ± 0.40 cm) had smaller translation compared with the MR group (0.54 ± 0.33 cm, P = 0.017) and control group (0.67 ± 0.36 cm, P = 0.028). No significant difference was detected in the other DOFs during the gait cycle. Significant difference was detected in extension/flexion, internal/external rotation, adduction/abduction, proximal/distal and medial/lateral among MR, SR and healthy knees. Conclusion After TKA, patients have altered gait kinematics compared with the control group. MR and SR design showed varied characteristics in 6 DOF gait kinematics, which could be the cause of the difference in functional outcome.

Abstract Background Strength deficits, muscle imbalances, and quadriceps inhibition are common after the total knee arthroplasty (TKA). It was suggested that theoretically single radius (SR) femoral protheses could provide longer extensor moment arm compared to the multiple radius (MR) design. However, quantitative evidence has not yet been reported. Thus, the aim of the study was to investigate the differences in isokinetic data and to compare the patient-reported outcome scores between TKA SR and MR design. Method The present retrospective study included 36 TKA involving 16 knees (9 patients) using SR design implant and 20 knees (11 patients) using MR design implant. The mean follow-up time was longer than 1 year. Isokinetic knee flexion and extension torques of the operated leg were evaluated at 60°/s and 180°/s. Quadriceps and hamstring torques and ratios, work and power were recorded. Angle-specific torques were also collected at different extension or flexion angles. Results Both groups showed improvement in knee society scores (KSS) and knee injury, and osteoarthritis outcome score (KOOS) after operation. Patients in SR group had significantly higher scores in KSS-knee, symptoms and activities of daily living KOOS sub-score than those in the MR group at the end of the follow-up. The peak knee flexion torque, peak knee extension torque and maximum knee flexion work were greater in SR group at 180°/s and 60°/s. At 60°/s, and SR group had higher average knee flexion power and average knee extension power than MR group. In the isometric contraction test, the knee extension torque was higher in SR group than in MR group. At 180°/s, SR group showed higher flexion torques at 30°, 40°, 50°, 60° compared with MR group. At 60°/s, SR group showed higher flexion torques at 30°, 40°, 50°, 60°, 80° when compared with MR group. Additionally, SR group also provided higher extension torques at 40°, 50°, 60° than the MR group. There were no differences in other isokinetic and isometric parameters between the two groups. Conclusion Femoral design exerted an influence on quadriceps and hamstring strength after TKA, and SR design shows advantages, in terms of higher extension and flexion strength, over MR design.

Traditional Chinese medicine (TCM) has demonstrated superior therapeutic effect for musculoskeletal diseases for thousands of years. Recently, the herbal extracts of TCM have received rapid advances in musculoskeletal tissue engineering (MTE). A literature review collecting both English and Chinese references on bioactive herbal extracts of TCM in biomaterial-based approaches was performed. This review provides an up-to-date overview of application of TCMs in the field of MTE, involving regulation of multiple signaling pathways in osteogenesis, angiogenesis, anti-inflammation, and chondrogenesis. Meanwhile, we highlight the potential advantages of TCM, opening the possibility of its extensive application in MTE. Overall, the superiority of traditional Chinese medicine turns it into an attractive candidate for coupling with advanced additive manufacturing technology.

Abstract Background Total hip arthroplasty is the most common orthopaedic procedure for the end-stage hip diseases. Periprosthetic bone loss is closely related to the increased risk of implant loosening and periprosthetic fractures, but the predictive value of periprosthetic bone mineral density (BMD) measured immediately after surgery has not yet been investigated. Methods From April 2015 to October 2017, 64 patients with femoral neck fracture, hip osteoarthritis, femoral head necrosis, or developmental dysplasia of the hip underwent unilateral total hip arthroplasty. Demographic data, bone mineral density of the hip and spine, periprosthetic BMD of 7 Gruen zones, and radiographic parameters measured preoperatively, 1 week, 3 months, and 12 months after surgery were collected. A p value

Abstract Background Revision total hip arthroplasty (THA) with large acetabular defect remains a challenge. Though trabecular metal (TM) cup and augments have been introduced in defect reconstruction with good result, the accurate positioning of implant is important to avoid complications. Therefore, we aimed to evaluate the usefulness of three-dimensional (3D) simulation and 3D model in assisting implant positioning during complex revision THA. Methods Sixteen patients (18 hips) who underwent revision THA with a Paprosky type III acetabular defect were analyzed retrospectively. Placement of acetabular cup and TM augments was simulated with 3D simulation software and 3D model preoperatively. Cup anteversion, abduction angle, and hip center were measured in each case preoperatively and postoperatively. Primary outcome was the percentage of outliers according to Lewinnek safe zone and Harris hip score (HHS). Secondary outcome was the correlation between the 3D planned and the postoperative value. Results The percentage of outliers was significantly corrected from 77.78% (14/18) preoperatively to 38.88% (7/18) postoperatively (p = 0.04). There was a significant correlation between mean planned cup anteversion and postoperative value (13.39 vs 11.99, r = 0.894; p < 0.001). There was a significant correlation between mean planned abduction and postoperative value (42.67 vs 44.91, r = 0.921, p < 0.001). The number of planned and used augments was the same in all the cases. In 15 cases (83.33%), the size of planned and used TM augments was the same. The HHS was significantly improved at final follow-up (80.94 vs 27.50, p < 0.001). No cases presented dislocation or radiological signs of loosening. Conclusion Preoperative 3D simulation and model were considered the useful method to assist implant positioning in revision THA with complex acetabular defect, with moderate to high accuracy and satisfied clinical outcome.

Intervertebral disc degeneration (IVDD) is an important risk factor of low back pain. We previously found upregulated markers of fibrosis, the late stage of chronic inflammation, in degenerated IVD with a small number of clinical specimens. Here, we aimed to study on a larger scale the association of cyclooxygenase 2 (COX2), an inflammation and/or pain marker, with IVDD. This study involved 107 LBP participants. The IVD degeneration level was graded on a 1–5 scale according to the Pfirrmann classification system. Discs at grades 1-3 were further grouped as white discs with grades 4-5 as black discs. We recorded baseline information about age, gender, body mass index (BMI), diabetes history, smoking history, and magnetic resonance imaging (MRI). Their association with IVDD was statistically analyzed. The expression level of COX2 was investigated by immunohistochemistry. The total integrated COX2 optical density (IOD), number of COX2-positive cells, and total cell number of each image were counted and analyzed by Image-Pro Plus software. The IOD and number of COX2-positive cells were divided by the total cell number to obtain COX2 expression density (IOD/cell) and COX2 positivity (cell+/cell). As a result, among the baseline information investigated, only age was found to have a significant association with IVDD. The IOD/cell was found to be significantly increased from grade 2 to grade 5, as well as in black discs compared to white discs. The cell+/cell displayed the same trend that it increased in highly degenerative discs compared to their counterparts. In conclusion, the expression of COX2 is associated with IVDD, which highlights COX2 as a biomarker for IVD degeneration and indicates the involvement of inflammation and pain signaling in IVDD.