Young human plasma-derived extracellular vesicles rescue and reactivate IL-1ß and TNF-α treated chondrocytes.

Osteoarthritis (OA) is a degenerative disease that affects millions of individuals worldwide. Despite its prevalence, the exact causes and mechanisms behind OA are still not fully understood, resulting in a lack of effective treatments to slow down or halt disease progression. Recent research has discovered that extracellular vesicles (EVs) present in the circulation of young mice have a remarkable ability to activate musculoskeletal stem cells in elderly mice. Conversely, EVs derived from elderly mice do not exhibit the same potential, indicating that EVs obtained from young individuals may hold promise to activate aging cells in degenerative tissue. However, it remains unknown whether EVs derived from young individuals can also address cartilage degeneration caused by aging. In this study, we first evaluated EVs derived from young human plasma (YEVs) and EVs derived from old human plasma (OEVs) in an in vitro experiment using chondrocytes. The results revealed that YEVs effectively stimulated chondrocyte proliferation and migration, while OEVs from old plasma did not exhibit a similar effect. Given that OA represents a more complex inflammatory microenvironment, we further determine whether the benefits of YEVs on chondrocytes can be maintained in this context. Our findings indicate that YEVs have the ability to positively regulate chondrocyte function and protect them against apoptosis induced by IL-1ß and TNF-α in an in vitro OA model. Furthermore, we discovered that lyophilized EVs could be stored under mild conditions without any alterations in their physical characteristics. Considering the exceptional therapeutic effects and the wide availability of EVs from young plasma, they hold significant promise as a potential approach to activate chondrocytes and promote cartilage regeneration in early-stage OA.

Mechanical overload-induced release of extracellular mitochondrial particles from tendon cells leads to inflammation in tendinopathy.

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.

In situ fabrication of an anisotropic double-layer hydrogel as a bio-scaffold for repairing articular cartilage and subchondral bone injuries.

Articular cartilage is a smooth and elastic connective tissue playing load-bearing and lubricating roles in the human body. Normal articular cartilage comprises no blood vessels, lymphatic vessels, nerves, or undifferentiated cells, so damage self-repair is very unlikely. The injuries of articular cartilage are often accompanied by damage to the subchondral bone. The subchondral bone mainly provides mechanical support for the joint, and the successful repair of articular cartilage depends on the ability of the subchondral bone to provide a suitable environment. Currently, conventional repair treatments for articular cartilage and subchondral bone defects can hardly achieve good results due to the poor self-repairing ability of the cartilage Here, we propose a bioactive injectable double-layer hydrogel to repair articular cartilage and subchondral bone. The hydrogel scaffold mimics the multilayer structure of articular cartilage and subchondral bone. Agarose was used as a common base material for the double-layer hydrogel scaffold, in which a sodium alginate (SA)/agarose layer was used for the repair of artificially produced subchondral bone defects, while a decellularized extracellular matrix (dECM)/agarose layer was used for the repair of articular cartilage defects. The double-layer hydrogel scaffold is injectable, easy to use, and can fill in the damaged area. The hydrogel scaffold is also anisotropic both chemically and structurally. Animal experiments showed that the surface of the new cartilage tissue in the double-layer hydrogel scaffold group was closest to normal articular cartilage, with a structure similar to that of hyaline cartilage and a preliminary calcified layer. Moreover, the new subchondral bone in this group exhibited many regular bone trabeculae, and the new cartilage and subchondral bone were mechanically bound without mutual intrusion and tightly integrated with the surrounding tissue. The continuous double-layer hydrogel scaffold prepared in this study mimics the multilayer structure of articular cartilage and subchondral bone and promotes the functional repair of articular cartilage and subchondral bone, favoring close integration between the newborn tissue and the original tissue.

Nano wear particles and the periprosthetic microenvironment in aseptic loosening induced osteolysis following joint arthroplasty.

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.

Bone turnover biomarkers predict one-year all-cause mortality and walking ability in geriatric hip fracture patients.

PURPOSE: To investigate the utility of serum C-terminal cross-linking telopeptides (ß-CTX) and procollagen type I N propeptide (PINP) for predicting one-year mortality and walking ability in Chinese geriatric hip fracture patients who underwent surgical interventions. METHOD: Elderly patients (≥ 60 years) who underwent surgical interventions for unilateral low-energy hip fracture from 2015 to 2020 in our center were included. Demographic data was retrospectively retrieved from the electronic medical database. The PINP and ß-CTX concentrations were measured before the surgery. The patients were divided into two groups according to the outcome of mortality and walking ability after hip surgery, respectively. ß-CTX and PINP were divided into four grades based on quartiles [Quartile(Q)1-4] for further analysis. All the variables with p < 0.1 in univariable analysis were included in a multivariable model. RESULTS: In univariable analysis, the levels of serum ß-CTX (p = 0.007) and PINP (p = 0.025) was associated with one-year mortality, while the association between levels of serum ß-CTX (p = 0.072) or PINP (p = 0.055) with one-year disability was marginally significant. After adjustment for confounders, the relative risk [OR (95 % CI), Q4 v sQ1, p-value] of one-year mortality and one-year disability were 7.28 (2.08-29.78, p = 0.003) and 3.97 (1.44-11.69, p = 0.009) for ß-CTX and 5.87 (1.70-23.80, p = 0.008) and 3.48 (1.30-9.93, p = 0.016) for PINP, respectively. The coefficient of determination, AUC and bias-corrected C-index of predictive models based on previously reported predictors were significantly improved after integrating ß-CTX or PINP. CONCLUSION: Higher serum ß-CTX and PINP are independently associated with an increased risk of one-year mortality and disability in patients with hip fractures. The application of BTMs improves the performance of currently available predictive models.

Stem cell therapy combined with core decompression versus core decompression alone in the treatment of avascular necrosis of the femoral head: a systematic review and meta-analysis.

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 < 0.00001), and with extracted stem cells (P = 0.0002). Likewise, stem cell group had a lower radiographic progression rate at 2- to 5-year follow-up [P = 0.003], when combined with structural grafting (P < 0.00001), and with extracted stem cells (P = 0.004). Stem cell therapy resulted in an overall lower THA conversion rate (P < 0.0001) except that at a follow-up longer than 5 years. CONCLUSION: Stem cell therapy combined with core decompression was more effective in preventing collapse, radiographic progression and conversion to THA. Trial Registration The current protocol has been registered in PROSPERO with the registration number: CRD42023417248.

Activating Endogenous Neurogenesis for Spinal Cord Injury Repair: Recent Advances and Future Prospects.

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.

Tail nerve electrical stimulation promoted the efficiency of transplanted spinal cord-like tissue as a neuronal relay to repair the motor function of rats with transected spinal cord injury.

Following transected spinal cord injury (SCI), there is a critical need to restore nerve conduction at the injury site and activate the silent neural circuits caudal to the injury to promote the recovery of voluntary movement. In this study, we generated a rat model of SCI, constructed neural stem cell (NSC)-derived spinal cord-like tissue (SCLT), and evaluated its ability to replace injured spinal cord and repair nerve conduction in the spinal cord as a neuronal relay. The lumbosacral spinal cord was further activated with tail nerve electrical stimulation (TNES) as a synergistic electrical stimulation to better receive the neural information transmitted by the SCLT. Next, we investigated the neuromodulatory mechanism underlying the action of TNES and its synergism with SCLT in SCI repair. TNES promoted the regeneration and remyelination of axons and increased the proportion of glutamatergic neurons in SCLT to transmit brain-derived neural information more efficiently to the caudal spinal cord. TNES also increased the innervation of motor neurons to hindlimb muscle and improved the microenvironment of muscle tissue, resulting in effective prevention of hindlimb muscle atrophy and enhanced muscle mitochondrial energy metabolism. Tracing of the neural circuits of the sciatic nerve and tail nerve identified the mechanisms responsible for the synergistic effects of SCLT transplantation and TNES in activating central pattern generator (CPG) neural circuits and promoting voluntary motor function recovery in rats. The combination of SCLT and TNES is expected to provide a new breakthrough for patients with SCI to restore voluntary movement and control their muscles.

Distribution of bone voids in the thoracolumbar spine in Chinese adults with and without osteoporosis: A cross-sectional multi-center study based on 464 vertebrae.

Bone void is a novel intuitive morphological indicator to assess bone quality but its use in vertebrae has not been described. This cross-sectional and multi-center study aimed to investigate the distribution of bone voids in the thoracolumbar spine in Chinese adults based on quantitative computed tomography (QCT). A bone void was defined as a trabecular net region with extremely low bone mineral density (BMD) (<40 mg/cm3), detected by an algorithm based on phantom-less technology. A total of 464 vertebrae from 152 patients (51.8 ± 13.4 years old) were included. The vertebral trabecular bone was divided into eight sections based on the middle sagittal, coronal, and horizontal planes. Bone void of the whole vertebra and each section were compared between healthy, osteopenia, and osteoporosis groups and between spine levels. Receiver operator characteristic (ROC) curves were plotted and optimum cutoff points of void volume between the groups were obtained. The total void volumes of the whole vertebra were 124.3 ± 221.5 mm3, 1256.7 ± 928.7 mm3, and 5624.6 ± 3217.7 mm3 in healthy, osteopenia, and osteoporosis groups, respectively. The detection rate of vertebrae with bone voids was higher and the normalized void volume was larger in the lumbar than in thoracic vertebrae. L3 presented the largest void (2165.0 ± 3396.0 mm3), while T12 had the smallest void (448.9 ± 699.4 mm3). The bone void was mainly located in the superior-posterior-right section (40.8 %). Additionally, bone void correlated positively with age and increased rapidly after 55 years. The most significant void volume increase was found in the inferior-anterior-right section whereas the least increase was found in the inferior-posterior-left section with aging. The cutoff points were 345.1 mm3 between healthy and osteopenia groups (sensitivity = 0.923, specificity = 0.932) and 1693.4 mm3 between osteopenia and osteoporosis groups (sensitivity = 1.000, specificity = 0.897). In conclusion, this study demonstrated the bone void distribution in vertebrae using clinical QCT data. The findings provide a new perspective for the description of bone quality and showed that bone void could guide clinical practice such as osteoporosis screening.

Preoperative Vitamin D Deficiency is Associated with Increased One-Year Mortality in Chinese Geriatric Hip Fracture Patients - A Propensity Score Matching Study.

Background: Vitamin D deficiency is a common comorbidity in geriatric hip fracture patients. However, there is still an ongoing debate regarding the influence of preoperative Vitamin D status on postoperative mortality in hip fracture patients. Methods: Elderly patients (≥60 years) who underwent surgical interventions for unilateral hip fracture from 2015 to 2020 in our center were included. We retrospectively retrieved the demographic data from the electronic medical database. Preoperative serum total 25-hydroxy-Vitamin D was set as the independent variable and patients were classified as the Vitamin D deficiency (<20ng/mL) and the control groups consequently. Clinical outcomes include all-cause mortality, walking ability, and major postoperative complications in the first postoperative year. Propensity score matching (PSM) was performed in a ratio of 1:1 in the two groups for further comparison. Results: A total of 210 patients were included and 121 patients (57.6%) were diagnosed with Vitamin D deficiency. Patients in the Vitamin D deficiency group were much older and therefore preferred peripheral nerve block, and had significantly higher proportions of females, preoperative dementia, higher ASA grade, and lower baseline serum albumin level. Overall, 79 patients were identified in the Vitamin D deficiency and control groups after PSM, respectively. Patients diagnosed with Vitamin D deficiency showed a significantly higher one-year mortality (21.5% vs 6.3%, P=0.011) and a much lower one-year independent walking rate (67.1% vs.84.8%, P=0.016) after the matching. Regarding the dataset before PSM and after PSM, the AUC for serum Vitamin D for predicting one-year mortality was 0.656 (P=0.006) and 0.695 (P=0.002), respectively. Conclusion: Our retrospective PSM-design study provides new evidence that Vitamin D deficiency was associated with a significantly higher mortality and poor walking ability in the first year after surgical intervention based on southern Chinese populations.

Baseline Knee Pain Predicts Long-Term Response of Intra-Articular Steroid Injection in Symptomatic Knee Osteoarthritis: Data from OAI.

OBJECTIVE: The current study aims to investigate the factors that could predict response to intra-articular corticosteroid injection (IACI) in patients with knee osteoarthritis (KOA). METHODS: Data of participants were retrieved from the Osteoarthritis Initiative database. Participants with at least one IACI treatment on single or bilateral knees within the first 5 years of follow-up were retrospectively included. Demographic data, clinical and radiographic variables were collected at both baseline and the first follow-up after IACI treatment. Positive response to IACI treatment was defined as >20% reduction of Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) pain score from V0 to V1. All the variables with P < 0.2 after the comparison between the response and non-response groups were included in a multivariable logistic regression model to identify independent response predictive patient-specific valuables. Receiver operating characteristic curves were performed to establish the cutoff values of independent predictors. RESULTS: The current study included a total of 385 participants (473 knees), with 155 and 318 knees classified into the response group and non-response group, respectively. Those with satisfied responses to IACI treatment had significantly higher WOMAC pain score (P < 0.001), disability score (P = 0.002), and stiffness score (P = 0.015) at the baseline. Baseline WOMAC pain score showed significant association with positive response to IACI treatment in multivariate logistic analysis and the best cutoff value was 5 points. The rate of analgesics utilization was lower (P = 0.014) in the response group than the non-response group after the IACI treatment. CONCLUSION: KOA patients with a baseline WOMAC pain score ≥5 are more likely to benefit from IACI treatment.

Anisotropic hydrogel fabricated by controlled diffusion as a bio-scaffold for the regeneration of cartilage injury.

Controlled fabrication of anisotropic materials has become a hotspot in materials science, particularly biomaterials, since the next generation of tissue engineering is based on the application of heterogeneous structures that can simulate the original biological complexity of the body. The current fabrication method of producing anisotropic materials involves expensive and highly specialized equipment, and not every conventional method can be applied to preparing anisotropic materials for corresponding tissue engineering. Anisotropic materials can be easily applied to a problem in tissue engineering: cartilage injury repairing. The articular cartilage consists of four spatially distinct regions: superficial, transitional, deep, and calcified. Each region has a specific extracellular matrix composition, mechanical properties, and cellular organization; this calls for the application of an anisotropic hydrogel. Controlled diffusion, under the assistance of buoyancy, has been considered a generalized method to prepare materials using a gradient. The diffusion of two solutions can be controlled through the difference in their densities. In addition to providing anisotropy, this method realizes the in situ formation of an anisotropic hydrogel, and simplifies the preparation process, freeing it from the need for expensive equipment such as 3D printing and microfluidics. Herein, an anisotropic hydrogel based on a decellularized extracellular matrix is fabricated and characterized. The as-prepared scaffold possessed specific chemical composition, physical properties, and physiological factor gradient. In vitro experiments ensured its biocompatibility and biological effectiveness; further in vivo experiments confirmed its application in the effective regeneration of cartilage injury.

Brain morphology changes after spinal cord injury: A voxel-based meta-analysis.

Objectives: Spinal 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. Methods: We 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. Results: Our 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. Conclusion: Atrophy 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 registration: https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42021279716, identifier: CRD42021279716.

Transcription and proteome changes involved in re-innervation muscle following nerve crush in rats.

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.

Challenges and perspectives of tendon-derived cell therapy for tendinopathy: from bench to bedside.

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.

Exosome-based strategy for degenerative disease in orthopedics: Recent progress and perspectives.

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.

Contralateral advanced radiographic knee osteoarthritis predicts radiographic progression and future arthroplasty in ipsilateral knee with early-stage osteoarthritis.

PURPOSE: To explore whether the severity of contralateral knee osteoarthritis (OA) is associated with OA progression in ipsilateral knee with early OA. METHODS: Knees in early OA (Kellgren-Lawrence grade (KLG):1-2) with intact baseline demographic and clinical data were retrieved from OAI database and defined as target knees. The target knees were divided into the exposure group (contralateral knees KLG 3 to 4) and the control group (contralateral knees KLG 0 to 2). Both groups underwent propensity score matching (PSM) concerning demographic data, as well as radiographic and clinical outcomes at the baseline. The primary outcome was the upgrade of KLG in the target knee in the first 12 and 24 months. The secondary outcome was the incidence of knee arthroplasty in ipsilateral knee during the first 108 months. RESULTS: One thousand seven hundred fifty-two knees were included, with 449 in the exposure cohort and 1276 in the control cohort. Four hundred thirty-four knees in each group were matched after PSM. Target knees in the exposure cohort showed a significantly higher rate of radiographic progression in the first 12 months (12.9% vs. 5.1%, P < 0.001) and 24 months (19.6% vs. 8.1%, P < 0.001). As for the risk of future arthroplasty, a significant difference was also found between the two groups (7.8% vs. 4.0%, P = 0.02). Kaplan-Meier analysis showed that the 108-month accumulated knee survival rate was significantly lower in the exposure group (P = 0.01). CONCLUSION: The ipsilateral knee with early-stage OA is prone to have worse early to mid-, and long-term prognosis in the circumstance of contralateral radiographic advanced knee OA. Key Points •Identifying early knee osteoarthritis (OA) with a high risk of radiographic progression and future arthroplasty enables early personalized intervention. •This is a novel study to investigate the relationship between the risk of future arthroplasty and contralateral knee status. •Propensity score matching holds promise to minimize selection bias in observational studies. •Knees with early OA are prone to have a high risk of radiographic progression and future arthroplasty in the circumstance of contralateral advanced knee OA.

[Three-dimensional morphological study of the effect of false acetabulum on the femoral structure in Crowe type â £ developmental dysplasia of the hip].

Objective: To explore the effect of false acetabulum on the development and anatomical morphology of proximal femur in Crowe type Ⅳ developmental dysplasia of the hip (DDH), providing a theoretical basis for the development of femoral reconstruction strategy and prosthesis selection for total hip arthroplasty. Methods: The medical records of 47 patients (54 hips) with Crowe type Ⅳ DDH between February 2008 and March 2020 were retrospectively analyzed, of which 21 patients (26 hips) were Crowe type Ⅳa (type Ⅳa group) and 26 patients (28 hips) were Crowe type Ⅳb (type Ⅳb group). There was no significant difference in general data such as gender, age, height, weight, body mass index, and side between the two groups ( P>0.05), which were comparable. The height of femoral head dislocation, the height of pelvis, and the proportion of dislocation were measured based on preoperative anteroposterior pelvic X-ray film. Based on the preoperative femoral CT scan data, the anatomical parameters of the femur and femoral medullary cavity were measured after three-dimensional reconstruction using Mimics19.0 software to calculate the canal fare index; and the femoral medullary cavity parameters were matched with the modular S-ROM prosthesis parameters. Results: The results of X-ray film measurement showed that the height of femoral head dislocation and the proportion of dislocation in type Ⅳa group were significantly higher than those in type Ⅳb group ( P<0.05). There was no significant difference in the height of pelvis between the two groups ( P>0.05). The results of CT three-dimensional reconstruction measurements showed that compared with the type Ⅳb group, the type Ⅳa group had less isthmus height, smaller femoral head, shorter femoral neck, narrower neck-shaft angle, increased anteversion angle, and higher greater trochanter, and the differences were significant ( P<0.05). There was no significant difference in the height of femoral head, femoral offset, and height difference between greater trochanter and femoral head between the two groups ( P>0.05). There was no significant difference in the mediolateral width (ML), anteroposterior width (AP), and diameter of the isthmus (Ci level) and the AP of the medullary cavity in the plane 40 mm distal to the most prominent point on the medial side of the lesser trochanter (C -40 level) ( P>0.05), and the size of medullary cavity was significantly smaller in type Ⅳa group than in type Ⅳb group at the other levels ( P<0.05). Compared with the type Ⅳb group, the difference between the outer diameter of the prosthetic sleeve and the diameter of the medullary cavity fitting circle in the plane where the center of femoral head rotation was located from the medial most prominent point of the lesser trochanter (C 0 level) in type Ⅳa group was smaller, and the proportion of negative values was greater ( P<0.05). The difference between the longest diameter of the prosthetic sleeve triangle and the ML of the medullary cavity in the plane 10 mm proximal to the most prominent point on the medial side of the lesser trochanter (C +10 level) in type Ⅳa group was smaller, and the proportion of negative values was greater ( P<0.05). Conclusion: False acetabulum has a significant impact on the morphology of the proximal femur and medullary cavity in patients with Crowe type Ⅳ DDH, and the application of three-dimensional reconstruction technique can accurately evaluate the femoral morphology and guide the selection of femoral prosthesis.

Three-dimensional morphological analysis of true acetabulum in Crowe type IV hip dysplasia via standard-sized cup-simulated implantation.

Background: Acetabular reconstruction in Crowe type IV developmental dysplasia of the hip (DDH) can be a challenging procedure for surgeons. A high risk of acetabular revision has been reported to be associated with extremely small acetabular prostheses. However, to our knowledge, quantitative morphological and coverage evaluations of the true acetabulum in Crowe IV hips have been infrequently conducted. Useful bony landmarks for acetabular reconstruction can also facilitate satisfactory intraoperative implantation. The aim of the present study was to investigate the anatomical size, orientation angles, and 2/3-dimensional (2D/3D) coverage parameters of the true acetabulum in Crowe IV hips; evaluate the feasibility of standard cup (>44 mm) implantation at the true acetabulum in Crowe IV hips; and identify the optimal position and useful bony landmarks of the acetabular reaming center in Crowe IV hips. Methods: A total of 42 Crowe IV hips in 37 patients and 36 normal hips were included in this study. Based on pelvic 3D computed tomography (CT) reconstruction, anatomical size and integral volume of the true acetabulum were measured quantitatively. Through standard-size cup-simulated implantation, morphological assessments of the true acetabulum included Cup-CE, Cup-Sharp, acetabular anteversion angle, and thickness of the medial wall. Acetabular sector angles (ASAs) and the component coverage ratio were measured to provide coverage indices. Acetabular reconstruction was also performed at different vertical levels to measure medial bone stock and 3D component coverage. Bony landmarks for optimal component center location were also determined. Results: The anatomic shape and volume of the acetabular triangle were significantly smaller in Crowe IV hips. Compared with the control group, the dysplastic acetabulum was more anteverted and abductive, with a thicker medial wall. According to the true acetabulum, bone stock was relatively sufficient in the posterior direction and prominently deficient in the anterosuperior and superior direction. The average 3D component coverage reached 79.89% by standard-sized cup implantation, with the most satisfactory coverage achieved at the true acetabulum (at the level of 13.32 mm above the transverse acetabular ligament). Regarding the component opening plane, the optimal component center was located at the midpoint between the superolateral and posteroinferior points of the true acetabulum. Conclusions: The most satisfactory coverage was achieved at the level of the true acetabulum, of which the most prominent deficiency was mainly located in the anterosuperior and superior directions. The optimal component center was determined to be the midpoint between the superolateral and posteroinferior points of the true acetabulum.

Transtibial pull-out repair of lateral meniscus posterior root is beneficial for graft maturation after anterior cruciate ligament reconstruction: a retrospective study.

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 (ß = 0.304, P = 0.049) and LME (ß = 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.