Mechanical stimulation promotes fibrochondrocyte proliferation by activating the TRPV4 signaling pathway during tendon-bone insertion healing: CCN2 plays an important regulatory role.

Background: We previously confirmed that mechanical stimulation is an important factor in the repair of tendon-bone insertion (TBI) injuries and that mechanoreceptors such as transient receptor potential ion-channel subfamily V member 4 (TRPV4; also known as transient receptor potential vanilloid 4) are key to transforming mechanical stimulation into intracellular biochemical signals. This study aims to elucidate the mechanism of mechanical stimulation regulating TRPV4. Methods: Immunohistochemical staining and western blotting were used to evaluate cartilage repair at the TBI after injury. The RNA expression and protein expression of mechanoreceptors and key pathway molecules regulating cartilage proliferation were analyzed. TBI samples were collected for transcriptome sequencing to detect gene expression. Calcium-ion imaging and flow cytometry were used to evaluate the function of TPRV4 and cellular communication network factor 2 (CCN2) after the administration of siRNA, recombinant adenovirus and agonists. Results: We found that treadmill training improved the quality of TBI healing and enhanced fibrochondrocyte proliferation. The transcriptome sequencing results suggested that the elevated expression of the mechanistically stimulated regulator CCN2 and the exogenous administration of recombinant human CCN2 significantly promoted TRPV4 protein expression and fibrochondrocyte proliferation. In vitro, under mechanical stimulation conditions, small interfering RNA (siRNA)-CCN2 not only inhibited the proliferation of primary fibrochondrocytes but also suppressed TRPV4 protein expression and activity. Subsequently, primary fibrochondrocytes were treated with the TRPV4 agonist GSK1016790A and the recombinant adenovirus TRPV4 (Ad-TRPV4), and GSK1016790A partially reversed the inhibitory effect of siRNA-CCN2. The phosphoinositide 3-kinase/ protein kinase B (PI3K/AKT) signaling pathway participated in the above process. Conclusions: Mechanical stimulation promoted fibrochondrocyte proliferation and TBI healing by activating TRPV4 channels and the PI3K/AKT signaling pathway, and CCN2 may be a key regulatory protein in maintaining TRPV4 activation.

Advancements and regulations of biomanufacturing cell-based cartilage repair therapies.

Cell-based therapies for cartilage repair, including autologous chondrocyte implantation and allogeneic stem cell treatments, show great promise but face challenges due to high costs and regulatory hurdles. This review summarizes available and investigational products, focusing on allogeneic therapies and the impact of diverse regulatory landscapes on their clinical translation.

Three-dimensional gas-foamed scaffolds decorated with metal phenolic networks for cartilage regeneration.

Inflammation is a major impediment to the healing of cartilage injuries, yet bioactive scaffolds suitable for cartilage repair in inflammatory environments are extremely rare. Herein, we utilized electrospinning to fabricate a two-dimensional nanofiber scaffold (2DS), which was then subjected to gas foaming to obtain a three-dimensional scaffold (3DS). 3DS was modified with metal phenolic networks (MPNs) composed of epigallocatechin gallate (EGCG) and strontium ions (Sr2+) to afford a MPNs-modified 3D scaffold (3DS-E). Gas-foamed scaffold exhibited multilayered structure conducive to cellular infiltration and proliferation. Compared to other groups, 3DS-E better preserved chondrocytes under interleukin (IL)-1ß induced inflammatory environment, showing less apoptosis of chondrocytes and higher expression of cartilage matrix. Additionally, 3DS-E facilitated the regeneration of more mature cartilage in vivo, reduced cell apoptosis, and decreased the expression of pro-inflammatory cytokines. Taken together, 3DS-E may offer an ideal candidate for cartilage regeneration.

Does scaffold enhancement show significant superiority over microfracture alone for treating knee chondral defects? A systematic review and meta-analysis of randomised clinical trials.

PURPOSE: Chondral and osteochondral lesions in the knee are common conditions that significantly impair individuals' well-being and can lead to osteoarthritis, imposing substantial burdens on healthcare systems. The limited natural healing capacity of articular cartilage necessitates innovative treatment strategies. Microfracture (MF) is a widely used technique for knee chondral defects, but its long-term efficacy is often inadequate. Although recent randomised controlled trials have compared microfractures with scaffold-enhanced therapies, a comprehensive systematic review and meta-analysis are lacking. METHODS: An extensive literature search was conducted in PubMed and EMBASE databases following PRISMA guidelines. Inclusion criteria focused on randomised controlled trials (RCTs) comparing microfractures alone to matrix-induced chondrogenesis for knee chondral defects with at least a 12-month follow-up. Ten randomised controlled trials conducted between 2013 and 2024, enroling 378 patients, were included. RESULTS: The meta-analysis showed no significant superiority of scaffolds over MF (p > 0.05) in International Knee Documentation Committee, Knee Injury and Osteoarthritis Outcome, Visual Analog Scale, and Magnetic Resonance Observation of Cartilage Repair Tissue scores at 12 and 24 months. However, individual studies suggested the potential benefits of scaffolds, especially in long-term outcomes. Clinical improvements from MF typically decline after 2-3 years, underscoring the need for long-term follow-up in future research. CONCLUSION: Our meta-analysis shows no significant difference between MF and MF with scaffold in treating knee cartilage defects, though some long-term RCTs demonstrate statistically significant differences. The absence of a universally accepted algorithm for analysing knee chondral defects limits this study. Establishing reliable guidelines and standardised study protocols is essential to improve long-term patient outcomes and the quality of future papers. LEVEL OF EVIDENCE: Level I.

Influence of cartilage defects and a collagen gel on integrity of corresponding intact cartilage: a biomechanical in-vitro study.

INTRODUCTION: Numerous cartilage repair procedures have been developed for focal lesions to minimize suffering and possibly prevent the development of osteoarthritis with a focus on so-called one-step procedures. The aim of this work was to investigate the effects of both focal cartilage defects and a biomaterial (ChondroFiller) on the corresponding articular cartilage. MATERIALS AND METHODS: On a friction test stand, 18 porcine osteochondral cylinders were tested in six experimental setups under cyclic loading (33 N) against a friction partner in saline solution. The friction partner (cartilage, bone, cartilage defect, cartilage defect with ChondroFiller) and the running times (1 hour and 6 hours) were varied. The damage to the osteochondral cylinders was assessed histologically using a visual damage classification. RESULTS: The cartilage versus bone group showed severe cartilage damage in both the one-hour and six-hour experiments, with an average damage score of 3.5. Damage in the cartilage versus cartilage defect group was moderate, with damage values of 2.5 (1 h) and 2.67 (6 h). The cartilage versus cartilage defect with ChondroFiller group showed a damage value of 2.67 for the one-hour and 2.5 for the six-hour trials. CONCLUSIONS: Even focal grade IV cartilage lesions can lead to significant damage to the corresponding cartilage in vitro. The damage could not be reduced by the use of ChondroFiller, likely because of the initial instability of this biomaterial. Therefore, a biomaterial must be stable in the beginning with regard to full weight-bearing, or joint loading should be delayed until stable filling of the defect is achieved.

Trends in Cartilage Repair Techniques for Chondral Defects in the Hip in Germany: An Epidemiological Analysis from 2006 to 2022.

Cartilage repair techniques for chondral defects in the hip are crucial for treating conditions like femoroacetabular impingement, developmental dysplasia, and osteonecrosis, especially in young patients to delay the progression of osteoarthritis. This study aims to present age and sex distributions and trends in hip-preserving surgeries in Germany from 2006 to 2022, analyzing 116,179 procedures using the German OPS coding system. The procedures were categorized into three groups: debridement, refixation, and regeneration. Arthroscopy was more common than arthrotomy (98,916 vs. 17,263). Males underwent more procedures than females (63,771 vs. 52,408). Debridement had a monomodal age distribution peaking at 43.42 years, while refixation and regeneration exhibited bimodal patterns. Regenerative procedures were primarily performed on younger patients (average 27.73 years). A Joinpoint analysis showed an initial increase in procedures, peaking around 2013, followed by a decline. Arthroscopic procedures peaked at approximately 9000 in 2013, whereas arthrotomies peaked at around 1200 after 2014. The decline in procedures post-2013 may reflect refined surgical indications and a shift towards outpatient settings. These findings underscore the trend towards minimally invasive, scaffold-based treatments, with regenerative techniques showing promising outcomes in younger patients. Future research should focus on prospective comparative studies and cost-benefit analyses to guide clinical decision-making.

Exosomes derived from primary cartilage stem/progenitor cells promote the repair of osteoarthritic chondrocytes by modulating immune responses.

BACKGROUND: Exosomes derived from primary chondrogenic stem/progenitor cells (CSPCs-EXOs) show promise in cartilage repair due to their immunomodulatory and regenerative properties. However, their specific therapeutic potential in osteoarthritis (OA), especially in modulating immune responses and enhancing chondrocyte function, requires further exploration. This study aims to clarify CSPCs-EXOs' effects on OA by investigating their role in chondrocyte proliferation, migration, inflammation inhibition, and cartilage regeneration. METHODS: A rat model of osteoarthritis was established using monosodium iodoacetate (MIA). CSPCs-EXOs were isolated and characterized before being administered to the OA rats. Comprehensive transcriptomic analysis was conducted to identify differentially expressed genes (DEGs) and signaling pathways influenced by CSPCs-EXOs. Histopathological evaluation of cartilage tissue, immunohistochemistry, and in vitro assays were performed to assess chondrocyte proliferation, migration, inflammation, and intracellular environmental changes. RESULTS: CSPCs-EXOs treatment significantly reduced OA-induced cartilage damage, shown by improved histopathological features, increased chondrocyte proliferation, migration, and enhanced cartilage matrix integrity. CSPCs-EXOs uniquely modulated immune pathways and enhanced cellular repair, setting them apart from traditional treatments. Transcriptomic analysis revealed regulation of immune response, inflammation, oxidative stress, and DNA repair pathways. CSPCs-EXOs downregulated inflammatory cytokines (TNF, IL-17) and upregulated pathways for cellular proliferation, migration, and metabolism. They also altered splicing patterns of DNA repair enzymes, indicating a role in boosting repair mechanisms. CONCLUSIONS: CSPCs-EXOs promote cartilage repair in osteoarthritis by modulating immune responses, inhibiting inflammation, and improving the intracellular environment. These findings emphasize their innovative therapeutic potential and offer key insights into their regenerative mechanisms, positioning CSPCs-EXOs as a promising strategy for OA treatment and a foundation for future clinical applications in cartilage tissue engineering and regenerative medicine.

Three-Dimensional Printed Silk Fibroin/Hyaluronic Acid Scaffold with Functionalized Modification Results in Excellent Mechanical Strength and Efficient Endogenous Cell Recruitment for Articular Cartilage Regeneration.

Treatment of articular cartilage remains a great challenge due to its limited self-repair capability. In tissue engineering, a scaffold with both mechanical strength and regenerative capacity has been highly desired. This study developed a double-network scaffold based on natural biomaterials of silk fibroin (SF) and methacrylated hyaluronic acid (MAHA) using three-dimensional (3D) printing technology. Structural and mechanical characteristics of the scaffold was first investigated. To enhance its ability of recruiting endogenous bone marrow mesenchymal stem cells (BMSCs), the scaffold was conjugated with a proven BMSC-specific-affinity peptide E7, and its biocompatibility and capacity of cell recruitment were assessed in vitro. Animal experiments were conducted to evaluate cartilage regeneration after transplantation of the described scaffolds. The SF/HA scaffolds exhibited a hierarchical macro-microporous structure with ideal mechanical properties, and offered a 3D spatial microenvironment for cell migration and proliferation. In vitro experiments demonstrated excellent biocompatibility of the scaffolds to support BMSCs proliferation, differentiation, and extracellular matrix production. In vivo, superior capacity of cartilage regeneration was displayed by the SF/MAHA + E7 scaffold as compared with microfracture and unconjugated SF/MAHA scaffold based on macroscopic, histologic and imaging evaluation. In conclusion, this structurally and functionally optimized SF/MAHA + E7 scaffold may provide a promising approach to repair articular cartilage lesions in situ.

Mesenchymal Stem Cells and Secretome as a New Possible Approach to Treat Cartilage Damage: An In Vitro Study.

Introduction: Osteoarthritis is a degenerative condition of the cartilage, often common among the population and occurs frequently with aging. Many factors are decisive for the development of its pathogenesis such as age, obesity, trauma, mechanical load, and modification of synovial biology. The main features of osteoarthritis are chondrocytes and cartilage matrix loss, which lead to pain, loss of function of the whole joint, and disability, representing a relevant health problem. Recently, a new therapeutic approach based on cell therapy has been studying the regenerative ability of mesenchymal stem cells for osteoarthritic chondrocytes. Aim: This in vitro study clarifies the regenerative effects of multipotent adipose-derived stem cells and the pluripotent amniotic epithelial stem cells on arthrosis chondrocytes by performing co-culture experiments. Methods: We studied the regenerative potential of secretome (soluble factors and extracellular vesicles), mesenchymal stem cells, and the adipose stromal vascular fraction. The regenerative effects were evaluated by gene and protein expression analysis of articular cartilage-specific genes and proteins like col2a1, acan, and sox9. Results: Mesenchymal stem cells, secretome, and adipose stromal vascular fractions influenced the cartilage genes and protein expression. Conclusions: The results indicate that the treatment with mesenchymal stem cells could be the best biological approach for cartilage regenerative medicine.

Outcomes After Osteochondral Allograft Transplantation of the Medial Femoral Condyle in Patients With Varus and Nonvarus Alignment.

BACKGROUND: Fresh osteochondral allograft (OCA) transplantation is an effective technique for the treatment of focal chondral and osteochondral defects in the knee. Coronal-plane malalignment leads to increased contact forces within a compartment and subsequently the cartilage repair site and may lead to higher failure rates. However, the magnitude of the effect of coronal-plane malalignment on graft survivorship and clinical outcomes has not been well characterized. PURPOSE: To evaluate how varus malalignment affects graft survival and patient-reported outcomes after isolated OCA transplantation of the medial femoral condyle (MFC). STUDY DESIGN: Cohort study; Level of evidence, 3. METHODS: A total of 70 patients (74 knees) who underwent primary OCA transplantation of the MFC between 2005 and 2019 were identified from a prospectively collected single-surgeon cartilage registry with a minimum 2-year follow-up. Coronal-plane alignment was evaluated utilizing standing hip-to-ankle radiographs. OCA failure, defined as removal of the graft or conversion to arthroplasty, and reoperations were recorded. Patient-reported outcomes were obtained preoperatively and postoperatively using the International Knee Documentation Committee score, Knee injury and Osteoarthritis Outcome Score, modified Merle d'Aubigné-Postel score, and overall patient satisfaction score. RESULTS: The mean mechanical tibiofemoral angle for patients with varus alignment was 3.9° of varus (range, 1.1° to 8.9°) and for patients with nonvarus alignment it was 0.02° of valgus (range, 3.6° varus to 4.6° valgus). Graft survivorship was 95.3% in the varus group and 95.8% in the nonvarus group (P = .918) at 5 years postoperatively. Reoperations after OCA transplantation occurred in 14.0% of the varus group and 22.6% of the nonvarus group (P = .336). The mean International Knee Documentation Committee total score improved from 45.2 preoperatively to 74.8 at latest follow-up in the varus group and from 40.5 preoperatively to 72.3 at latest follow-up in the nonvarus group. Patient satisfaction was >85%. CONCLUSION: Patients undergoing isolated OCA transplantation of the MFC had high rates (>90%) of graft survivorship and significant improvements in pain and function. Patients with mild preexisting varus malalignment were found to have no difference in the failure rate or clinical outcomes compared with patients with nonvarus alignment.

Drug-Loaded Bioscaffolds for Osteochondral Regeneration.

Osteochondral defect is a complex tissue loss disease caused by arthritis, high-energy trauma, and many other reasons. Due to the unique structural characteristics of osteochondral tissue, the repair process is sophisticated and involves the regeneration of both hyaline cartilage and subchondral bone. However, the current clinical treatments often fall short of achieving the desired outcomes. Tissue engineering bioscaffolds, especially those created via three-dimensional (3D) printing, offer promising solutions for osteochondral defects due to their precisely controllable 3D structures. The microstructure of 3D-printed bioscaffolds provides an excellent physical environment for cell adhesion and proliferation, as well as nutrient transport. Traditional 3D-printed bioscaffolds offer mere physical stimulation, while drug-loaded 3D bioscaffolds accelerate the tissue repair process by synergistically combining drug therapy with physical stimulation. In this review, the physiological characteristics of osteochondral tissue and current treatments of osteochondral defect were reviewed. Subsequently, the latest progress in drug-loaded bioscaffolds was discussed and highlighted in terms of classification, characteristics, and applications. The perspectives of scaffold design, drug control release, and biosafety were also discussed. We hope this article will serve as a valuable reference for the design and development of osteochondral regenerative bioscaffolds and pave the way for the use of drug-loaded bioscaffolds in clinical therapy.

Harnessing Peptide-Based Hydrogels for Enhanced Cartilage Tissue Engineering.

Cartilage tissue engineering remains a formidable challenge due to its complex, avascular structure and limited regenerative capacity. Traditional approaches, such as microfracture, autografts, and stem cell delivery, often fail to restore functional tissue adequately. Recently, there has been a surge in the exploration of new materials that mimic the extracellular microenvironment necessary to guide tissue regeneration. This review investigates the potential of peptide-based hydrogels as an innovative solution for cartilage regeneration. These hydrogels, formed via supramolecular self-assembly, exhibit excellent properties, including biocompatibility, ECM mimicry, and controlled biodegradation, making them highly suitable for cartilage tissue engineering. This review explains the structure of cartilage and the principles of supramolecular and peptide hydrogels. It also delves into their specific properties relevant to cartilage regeneration. Additionally, this review presents recent examples and a comparative analysis of various peptide-based hydrogels used for cartilage regeneration. The review also addresses the translational challenges of these materials, highlighting regulatory hurdles and the complexities of clinical application. This comprehensive investigation provides valuable insights for biomedical researchers, tissue engineers, and clinical professionals aiming to enhance cartilage repair methodologies.

High-precision bioactive scaffold with dECM and extracellular vesicles targeting 4E-BP inhibition for cartilage injury repair.

The restoration of cartilage injuries remains a formidable challenge in orthopedics, chiefly attributed to the absence of vascularization and innervation in cartilage. Decellularized extracellular matrix (dECM) derived from cartilage, following antigenic removal through decellularization processes, has exhibited remarkable biocompatibility and bioactivity, rendering it a viable candidate for cartilage repair. Additionally, extracellular vesicles (EVs) generated from cartilage have demonstrated a synergistic effect when combined with dECM, potentially mitigating the inhibitory impact on protein synthesis by phosphorylating 4ebp, thereby promoting the synthesis of cartilage-related proteins such as collagen. In pursuit of this objective, we have innovated a novel bioink and repair scaffold characterized by exceptional biocompatibility, bioactivity, and biodegradability, establishing a tissue-specific microenvironment conducive to chondrogenesis. Within rat osteochondral defects, the biologically active scaffold successfully prompted the formation of transparent cartilage, featuring adequate mechanical strength, favorable elasticity, and dECM deposition indicative of cartilage. In summary, this study has effectively engineered a hydrogel bioink tailored for cartilage repair and devised a bioactive cartilage repair scaffold proficient in instigating cell differentiation and fostering cartilage repair.

Culturing Osteochondral Explants Under Rotary Shaking or After Removing Bone Marrow Elements Increases Explant Cellular Viability.

BACKGROUND: Reduced viability in the deepest zones of osteochondral allografts (OCAs) can weaken the subchondral interface, potentially increasing the risk of failure. This reduction may result from nutritional imbalances due to uneven media distribution or interference from bone marrow elements. PURPOSE: To investigate whether culturing OCAs using a rotary shaker or removing the bone marrow elements would increase graft cellular viability. STUDY DESIGN: Controlled laboratory study. METHODS: Bovine osteochondral explants were stored for 28 days at 4°C under 3 different conditions (n = 6 explants per group): static (control group), rotary shaker at 150 rpm (shaker group), and static after removal of bone marrow elements using a Waterpik device (Waterpik group). Chondrocyte viability was assessed using live/dead staining across the entire tissue and in each zone (superficial, middle, deep). Subchondral bone viability was assessed using TUNEL (terminal deoxynucleotidal transferase-mediated biotin-deoxyuridine triphosphate nick-end labeling) staining to detect apoptotic cells. RESULTS: Both shaker (64.2%; P = .010) and Waterpik (65.6%; P = .005) conditions showed significantly higher chondrocyte viability compared with control (49.8%). When samples were analyzed by zone, the shaker and Waterpik groups displayed higher cellular viability at the middle zone (shaker = 60.6%, P < .001; Waterpik = 56.1%, P < .001) and deep zone (shaker = 63.1%, P = .018; Waterpik = 61.5%, P = .025) than the control group (25.6% at middle zone; 32.8% at deep zone). Additionally, shaker (56.7%; P = .018) and Waterpik (51.4%; P = .007) groups demonstrated a lower percentage of apoptotic cells in subchondral bone compared with control (88.0%). No significant differences were observed between the shaker and Waterpik groups in any of the analyses. CONCLUSION: Both rotary shaking and removal of bone marrow elements during storage of osteochondral explants led to higher chondrocyte viability at the middle and deep zones of the graft compared with the static storage condition. Enhancing nutrition delivery to the graft could improve its quality, potentially improving outcomes of OCA transplantation. CLINICAL RELEVANCE: The use of a rotary shaker or the removal of bone marrow elements may significantly improve the culture conditions, increasing graft viability and integrity after OCA storage.

Angiogenesis unveiled: Insights into its role and mechanisms in cartilage injury.

Osteoarthritis (OA) commonly results in compromised mobility and disability, thereby imposing a significant burden on healthcare systems. Cartilage injury is a prevalent pathological manifestation in OA and constitutes a central focus for the development of treatment strategies. Despite the considerable number of studies aimed at delaying this degenerative process, their outcomes remain unvalidated in preclinical settings. Recently, therapeutic strategies focused on angiogenesis have attracted the growing interest from researchers. Thus, we conducted a comprehensive literature review to elucidate the current progress in research and pinpoint research gaps in this domain. Additionally, it provides theoretical guidance for future research endeavors and the development of treatment strategies.

Development of scaffold-free tissue-engineered constructs derived from mesenchymal stem cells with serum-free media for cartilage repair and long-term preservation.

Synovial mesenchymal stem cells (sMSCs) have great potential for cartilage repair, but their therapeutic design to avoid adverse effects associated with unknown factors remains a challenge. In addition, because long-term preservation is indispensable to maintain high quality levels until implantation, it is necessary to reduce their fluctuations. This study aimed to investigate the properties and feasibility of novel scaffold-free tissue-engineered constructs using serum-free media and to develop long-term preservation methods. sMSCs were cultured in serum-free media, seeded at high density in a monolayer, and finally developed as a sheet-like construct called "gMSC1". The properties of frozen gMSC1 (Fro-gMSC1) were compared with those of refrigerated gMSC1 (Ref-gMSC1) and then examined by their profile. Chondrogenic differentiation potential was analyzed by quantitative real-time polymerase chain reaction and quantification of glycosaminoglycan content. Xenografts into the cartilage defect model in rats were evaluated by histological staining. gMSC1 showed nearly similar properties independent of the preservation conditions. The animal experiment demonstrated that the defect could be filled with cartilage-like tissue with good integration to the adjacent tissue, suggesting that gMSC1 was formed and replaced the cartilage. Furthermore, several chondrogenesis-related factors were significantly secreted inside and outside gMSC1. Morphological analysis of Fro-gMSC1 revealed comparable quality levels to those of fresh gMSC1. Thus, if cryopreserved, gMSC1, with no complicated materials or processes, could have sustained cartilage repair capacity. gMSC1 is a prominent candidate in novel clinical practice for cartilage repair, allowing for large quantities to be manufactured at one time and preserved for a long term by freezing. Supplementary Information: The online version contains supplementary material available at 10.1007/s10616-024-00637-y.

[Advances in clinical repair techniques for localized knee cartilage lesions].

Objective: To summarize the classic and latest treatment techniques for localized knee cartilage lesions in clinical practice and create a new comprehensive clinical decision-making process. Methods: The advantages and limitations of various treatment methods for localized knee cartilage lesions were summarized by extensive review of relevant literature at home and abroad in recent years. Results: Currently, there are various surgical methods for treating localized knee cartilage injuries in clinical practice, each with its own pros and cons. For patients with cartilage injuries less than 2 cm 2 and 2-4 cm 2 with bone loss are recommended to undergo osteochondral autograft (OAT) and osteochondral allograft (OCA) surgeries. For patients with cartilage injuries less than 2 cm 2 and 2-4 cm 2 without bone loss had treatment options including bone marrow-based techniques (micro-fracture and ogous matrix induced chondrogenesis), autologous chondrocyte implantation (ACI)/matrix-induced ACI, particulated juvenile allograft cartilage (PJAC), OAT, and OCA. For patients with cartilage injuries larger than 4 cm 2 with bone loss were recommended to undergo OCA. For patients with cartilage injuries larger than 4 cm 2 without bone loss, treatment options included ACI/matrix-induced ACI, OAT, and PJAC. Conclusion: There are many treatment techniques available for localized knee cartilage lesions. Treatment strategy selection should be based on the size and location of the lesion, the extent of involvement of the subchondral bone, and the level of evidence supporting each technique in the literature.

Treatment of osteochondral injuries of the humeral head using fresh osteochondral allograft transplantation.

Background: Large osteochondral lesions of the humeral head can result from locked posterior dislocations, avascular necrosis, and osteochondritis dissecans. Fresh osteochondral allograft (OCA) transplantation is a treatment option for young patients with focal osteochondral defects of the humeral head. The purpose of this case series was to assess graft survivorship, subjective patient-reported outcomes, and satisfaction among 7 patients who underwent OCA transplantation of the humeral head. Methods: We identified 7 patients who underwent humeral head OCA transplantation between 2008 and 2017. A custom questionnaire including the American Shoulder and Elbow Surgeons score, Quick Disabilities of the Arm, Shoulder, and Hand score (QuickDash), Likert satisfaction, and reoperations was mailed to each patient. Clinical failure was defined as further surgery that involved removal of the allograft. Results: Median follow-up duration was 10 years (range, 4.6 to 13.5 years) with a median age of 21.6 years (range, 18.5 to 43.5 years). Most patients (86%) reported improved function and reduced pain. At the final follow-up, 71% of patients reported ongoing problems with their shoulder including pain, stiffness, clicking/grinding, limited range of motion, and instability. Return to recreational activities was high at 86% but 43% expressed limitations with activity due to their shoulder. Overall satisfaction was high at 71% with mean American Shoulder and Elbow Surgeons and QuickDASH scores at 62.4 and 29.2, respectively. Reoperation after OCA occurred in 1 patient (14%). Conclusion: Among this case series of 7 patients who underwent OCA transplantation of the humeral head, patient satisfaction was high at 10-year follow-up and most returned to recreational activity although most also had persistent shoulder symptoms.

Osteocyte-derived exosomes regulate the DLX2/wnt pathway to alleviate osteoarthritis by mediating cartilage repair.

BACKGROUND: Chondrocyte viability, apoptosis, and migration are closely related to cartilage injury in osteoarthritis (OA) joints. Exosomes are identified as potential therapeutic agents for OA. OBJECTIVE: This study aimed to investigate the role of exosomes derived from osteocytes in OA, particularly focusing on their effects on cartilage repair and molecular mechanisms. METHODS: An injury cell model was established by treating chondrocytes with IL-1ß. Cartilage repair was evaluated using cell counting kit-8, flow cytometry, scratch test, and Western Blot. Molecular mechanisms were analyzed using quantitative real-time PCR, bioinformatic analysis, and Western Blot. An OA mouse model was established to explore the role of exosomal DLX2 in vivo. RESULTS: Osteocyte-released exosomes promoted cell viability and migration, and inhibited apoptosis and extracellular matrix (ECM) deposition. Moreover, exosomes upregulated DLX2 expression, and knockdown of DLX2 activated the Wnt pathway. Additionally, exosomes attenuated OA in mice by transmitting DLX2. CONCLUSION: Osteocyte-derived exosomal DLX2 alleviated IL-1ß-induced cartilage repair and inactivated the Wnt pathway, thereby alleviating OA progression. The findings suggested that osteocyte-derived exosomes may hold promise as a treatment for OA.