[Analysis of kinematic changes of hip joint after total hip arthroplasty].

Objective: To analyze the kinematic changes of the hip joint after total hip arthroplasty (THA) through three-dimensional gait analysis. Methods: Patients with hip joint diseases admitted between October 2022 and June 2023 were selected as the subjects. The patients who met the selective criteria were finally included in the THA group. The healthy volunteers matched with the THA group in the same age were included as the control group. Baseline data including age, gender, body mass index (BMI), and laterality were compared between the two groups. The Harris hip score (HHS) and the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) score were recorded preoperatively and at last follow-up in the THA group. Three-dimensional motion capture system was utilized to collect spatiotemporal parameters and kinematic data during walking, including stride length, cadence, and maximum/minimum values, range of motion (ROM) in hip joint abduction/adduction, external/internal rotation, and flexion/extension, as well as gait scores. Differences between the two groups were analyzed. Additionally, the correlation between gait scores and postoperative HHS and WOMAC scores were analyzed in the THA group. Finally, the kinematic data of each degree of freedom (DOF) were fitted into a gait diagram, and the dynamic changes of the 3-DOF of the hip joint during the gait cycle were quantitatively analyzed. Results: There was no significant difference in gender, age, laterality, and BMI between the two groups ( n=20, P>0.05). The mean follow-up time in the THA group was 9.9 months (range, 6-12 months). The HHS and WOMAC scores at last follow-up in the THA group showed significant improvement when compared with preoperative scores ( P<0.05). Gait scores were positively correlated with postoperative HHS score ( r=0.585, P=0.007) and negatively correlated with WOMAC score ( r=-0.619, P=0.004). There was no significant difference in stride length and cadence between the THA and control groups ( P>0.05), but gait score was significantly lower in the THA group than in the control group ( P<0.05). There was no significant difference in maximum and minimum values of flexion/extension, external/internal rotation, and abduction/adduction between the two groups ( P>0.05); however, ROM in the THA group was significantly lower than that in the control group ( P<0.05). There were significant differences between the two groups of flexion/extension in multiple phases of the gait cycle ( P<0.05). Conclusion: Early post-THA hip joint kinematics exhibit relative adduction, external rotation, and flexion during the gait cycle compared to normal individuals, with incomplete recovery of kinematic parameters in three degrees of freedom. Significant differences in flexion are observed at multiple phases of the gait cycle compared to normal individuals.

Preoperative transthoracic echocardiography does not lead to decreased postoperative mortality but with increased time to surgery and length of stay in Chinese geriatric hip fracture patients.

PURPOSE: The present study aimed to investigate the influence of preoperative TTE on postoperative short-term mortality, surgery delay, as well as other economic and clinical outcomes in Chinese geriatric hip fracture patients. METHODS: This retrospective, matched-cohort study enrolled geriatric hip fracture patients (≥ 60 years) who underwent surgical interventions at our center between 2015 and 2020. The primary exposure was inpatient preoperative TTE. Demographic and clinical data that were reported as risk factors for postoperative mortality were retrieved from the medical data center as the covariates. The primary clinical outcomes were all-cause mortality at 30 days, 90 days, 180 days, and 1 year. Time from hospital presentation to surgery, length of stay (LOS), inpatient cost, frequency of cardiology consultation and coronary angiography (CAG) were also assessed. The propensity score matching (PSM) was performed in a ratio of 1:1. RESULTS: 447 patients were identified and 216 of them received a preoperative TTE (48.3%). After successfully matching 390 patients (87.2%), patients receiving TTE showed significantly higher 30-day mortality (6.6% vs 2.0%, P = 0.044). But no significant difference was found in 90-day, 180-day, and 365-day mortality as well as the 1-year accumulated survival rate. Receipt of TTE was also associated with significant increases in LOS (13.6 days vs 11.4 days, P = 0.017), waiting time for surgery (5.9 days vs 4.3 days, P < 0.001), and lower proportion of receiving surgery within 48 h (7.2% vs. 26.2%, P < 0.001). According to the multivariable logistic analysis, only ejection fraction (30 days, 90 days), aorta diameter (30 days, 90 days, 180 days, 365 days), left ventricular posterior wall diameter (90 days, 180 days, 365 days), aortic valve velocity (90 days) and mitral valve A-peak (90 days, 180 days) were association with postoperative mortality among the 17 parameters in the TTE reports. Besides, TTE has no influence on the frequency of preoperative cardiology consultation. CONCLUSION: Preoperative TTE does not lead to decreased postoperative mortality but with increased time to surgery and length of stay in Chinese geriatric hip fracture patients. The predictive ability of TTE parameters is limited for postoperative mortality.

Intraoperative intravenous versus periarticular injection of glucocorticoids in improving clinical outcomes after total knee arthroplasty: A prospective, randomized and controlled study.

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.

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.

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.

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.

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.