Cartilage Repair Research Articles (Page 1)

The aim of this study was to investigate a biomimetic biodegradable cell-free osteochondral scaffold in a clinically relevant large animal model to quantify the early integration and regeneration phases after implantation. Bilateral critical-sized osteochondral defects were created in 14 sheep. One defect was filled with the scaffold, whereas the contralateral was left empty. The graft integration and regeneration tissue quality were evaluated at 14 and 30 days of follow-up. In particular, samples were evaluated for inflammation grade according to the ISO 10993-6 international standard biological evaluation of medical devices, macroscopic appearance graded according to a modified Fortier et al scoring system, histological quality according to a modified International Cartilage Repair Society (ICRS) II score, and the new trabecular bone formation with a micro-CT analysis. At 14 days, a higher defect filling was found in the scaffold group compared to the control in the gross analysis (p < 0.001). Low inflammation was observed in both groups, with a slight increase in the scaffold group at 30 days. The scaffold group had better histological scores, with a significantly higher mean global ICRS II score at 30 days compared to controls (p = 0.031). Finally, the mean percentage of new trabecular bone (BV/TV) was significantly higher in the scaffold group versus the control group, both at 14 days (11.5% (SD 4.5) and 5.2% (SD 2.3), respectively; p = 0.005) and at 30 days (28.0% (SD 8.1) and 8.8% (SD 5.0), respectively; p = 0.002). The tri-layered biomaterial showed good integration with surrounding tissues and new tissue growth promotion after 14 and 30 days post-surgery, with no safety concerns. In light of the development of appropriate postoperative rehabilitation programmes to prevent the risk of early implant failure while avoiding delays and providing a proper recovery path, this study provides support for the new cartilage field trend for this osteochondral scaffold, suggesting the possibility of safely shortening the postoperative rehabilitation phase after surgery.

Abstract The limited regenerative capacity of articular cartilage necessitates effective treatment methods for its repair. Infrapatellar fat pad (IPFP)-derived adipose stem cells (ASCs) demonstrate superior chondrogenic potential compared to subcutaneous adipose tissue (SCAT)-derived ASCs, making IPFP a promising source for cartilage regeneration. This study aimed to compare the quantitative expression of chondrogenic markers in mesenchymal stem cells (MSCs) derived from the IPFP and SCAT. Biopsy samples were collected from 25 patients undergoing knee osteoarthritis treatment. Histological and immunohistochemical analyses were performed on IPFP and SCAT samples, focusing on CD44, CD166, and SOX9 markers. The IPFP samples exhibited significantly higher relative numbers of CD44+ (13.28%), CD166+ (10.34%), and SOX9+ (7.30%) cells compared to SCAT samples, where values were 1.40%, 1.10%, and 0.90%, respectively. The differences were statistically significant (p &lt; 0.05). IPFP-ASCs showed enhanced stability in marker expression, suggesting their specialization for chondrogenic differentiation. IPFP is a superior source of MSCs for cartilage repair, with a significantly higher presence of CD44+, CD166+, and SOX9+ cells compared to SCAT. These findings highlight the potential of IPFP-derived ASCs in regenerative cartilage therapy and underscore the importance of their anatomical proximity to cartilage tissue.

Osteochondral defect is a severe health concern, particularly in the elderly, while, with limited medical treatment options. It is urgent to develop osteochondral regeneration scaffolds that integrate multiple biological cues to promote cartilage and subchondral bone repair simultaneously. In this study, osteochondral scaffolds featuring both a mechanical gradient and unidirectional micro-channels are constructed based on a bilayer hydrogel design. The soft layer, composed of a polymeric double network, mimics the mechanical properties of cartilage. The relatively stiff layer, reinforced with nanohydroxyapatite (nHAp), aligns with the subchondral bone feature. The combination of bilayer structure provides a mechanical cue to mimicthe heterogeneous modulus of the native osteochondral tissue. The bilayer design contributes to the differentiation of bone mesenchymal stem cells (BMSCs) into chondrocytes and osteoblasts, correspondingly. Moreover, the unidirectional micro-channels crossing the bilayer provide a topological cue, which facilitates the directional migration of cells. In vivo implanting in a rat osteochondral injury model demonstrates enhanced regeneration of cartilage and bone after 12 weeks. These findings suggest that the bilayer hydrogel scaffold, through the integration of mechanical and topological cues, offers a biomimetic 3D extracellular matrix with promising potential for osteochondral repair.

Mesenchymal stromal cell secretome in scaffold-based drug delivery: Advances, applications, and future directions.

Detailed rehabilitation protocols after stem cell treatment are lacking. This case highlights the rehabilitation of a patient treated with human umbilical cord blood-derived mesenchymal stem cell implantation for a large osteochondritis dissecans lesion of the knee. A 17-year-old male adolescent wrestler experienced persistent left knee pain for 1year, unresponsive to 6months of conservative treatment. MRI revealed a large osteochondritis dissecans lesion (38 × 18mm) in the lateral femoral condyle, which was treated with human umbilical cord blood-derived mesenchymal stem cell implantation. Rehabilitation was conducted in 4 phases. The protection phase (1-8wk) emphasized weight-bearing restrictions, continuous passive motion, and early gait training. The gait recovery phase (9-12wk) incorporated stationary cycling and open kinetic chain exercises. During the maturation phase (13-24wk), maximal strength and proprioception exercises were introduced with antigravity treadmill running. The final recovery phase (24-52wk) focused on plyometric drills and sport-specific activities. Team training resumed at 32weeks, and return to full competitive training occurred at 52weeks. The limb symmetry index for isokinetic knee-extensor strength and single-leg hop test reached 95.2% and 97.9%, respectively, by 12months, indicating near-complete functional recovery. The modified MRI of cartilage repair tissue score improved from 40 to 60 points between 1 and 3years postsurgery. Second-look arthroscopy revealed an International Cartilage Repair Society grade 1 at 35months. International Knee Documentation Committee scores increased from 17.2 preoperatively to 98.9 at 2years, while visual analog scale scores decreased from 10 to 2 over 3years. Accelerated weight bearing, early gait training, and phased strength exercises facilitated substantial improvements in function and cartilage healing in an adolescent wrestler with a large osteochondritis dissecans lesion. Further studies with larger cohorts are recommended to confirm these findings.

A pH-responsive nanocarrier delivered by carbine-crosslinked hydrogel paints for smart immunomodulation in arthroscopic cartilage repair

Osteoarthritis (OA) is a degenerative joint disease characterized by cartilage breakdown and chronic inflammation. Current therapies mainly relieve symptoms but do not halt disease progression. We developed collagen hydrogels incorporating propolis-loaded zeolitic imidazolate framework-8 (ZIF-8) nanoparticles (PROZIF) and menstrual blood-derived stem cells (MenSCs). Invitro assays evaluated microstructure, cell viability, anti-inflammatory activity, drug release, and cytoprotection. An osteoarthritis model was induced in rats by monosodium iodoacetate (MIA). Animals received intra-articular injections of hydrogels, and outcomes were assessed by histology, enzyme-linked immunosorbent assay (ELISA), knee swelling, and locomotor function. Collagen-PROZIF-MenSCs hydrogels with 2% nanoparticle content (COL-PROZIF-MenSCs-2) preserved MenSC viability, showed strong anti-inflammatory effects, and provided sustained propolis release. Invivo, this group significantly reduced cartilage degeneration, decreased tumor necrosis factor-alpha (TNF-α), interleukin-6 (IL-6), and interleukin-1 beta (IL-1β), and increased transforming growth factor-beta (TGF-β) and fibroblast growth factor (FGF) levels compared to controls. Knee swelling was reduced, and locomotor scores improved. Combining ZIF-8 nanoparticles with MenSCs in collagen hydrogels synergistically mitigated OA progression in rats by reducing inflammation and supporting cartilage repair. This approach demonstrates promise as a localized, cell- and drug-based therapy for OA, warranting further long-term and translational studies.

ObjectiveCurrently, there is a wide range of therapeutics that can be used to treat ankle osteoarthritis (OA), but none of them are able to fully restore the function of the ankle joint long-term. In this narrative review, we aim to summarize the current progress of using bone marrow aspirate concentrate (BMAC) for treating ankle OA.DesignPubMed was searched for publications that were published from 1990 until September 1, 2025 (moment of search). Key search terms were bone marrow aspirate concentrate and ankle OA. This yielded 17 hits, of which 10 were included in this narrative review.ResultsBMAC may enhance cartilage repair in ankle injuries and OA, especially when it is used in combination with other surgical techniques and biological treatments. However, the body of supporting evidence remains largely composed of Level II to IV studies (case-control and retrospective series). In addition, the independent role of BMAC remains unclear due to the lack of studies evaluating BMAC as a stand-alone treatment, as well as the unclear role that it plays as an adjuvant therapy.ConclusionsIn conclusion, the existing literature investigating BMAC for ankle OA is encouraging but remains inconclusive. High-quality randomized controlled trials with standardized protocols, longer follow-up, and head-to-head comparison against other treatment options are needed to establish both efficacy and cost-effectiveness. Establishing minimal reporting standards for BMAC composition is also critical to improve consistency across studies.

This study presents the development of a force-flow coupling mass transfer device, designed to explore the potential clinical applications of dynamic loading and osteochondral interface fluid flow in supporting drug therapy for cartilage injury repair. The device's stiffness was first validated under dynamic loading, followed by a quantitative analysis of tracer concentrations in cartilage using force-flow coupling. Hydrogel scaffolds were then evaluated for their mass transfer performance, with different peak stresses applied to investigate molecular transport mechanisms within cartilage. Experimental results showed that the stress-time curve of the device was consistent with that of the original fixture. Under the same peak stress, tracer concentration during peristaltic pump-driven bone-to-cartilage fluid transport was 1.40 times higher than that without flow. Mass transfer experiments with cartilage-hydrogel constructs further demonstrated that hydrogel scaffolds exhibited higher molar flow rates when the pump was activated compared to the static state, showing superior mass transfer performance relative to native cartilage. Peak stress regulation experiments revealed that dynamic loading enhanced tracer transport into the deep cartilage layer under constant flow conditions. The newly developed device facilitates experimental investigations of both native and artificial cartilage, elucidating the complex interactions between mechanical loading and osteochondral interface fluid dynamics. This technology provides crucial technical support for understanding cartilage repair mechanisms, optimizing drug delivery strategies, and evaluating the mass transfer performance of artificial cartilage under physiological loading conditions.

The effect of nigella sativa oil on healing in nasal septum perforations.

The promotion of cartilage regeneration by injectable photocurable gelatin hydrogel loaded with auto-concentrated growth factor.

Rheumatoid arthritis (RA) is a chronic autoimmune disease characterized by joint inflammation and dysfunction. Although existing treatments can alleviate symptoms, they lack a comprehensive and effective approach for treating RA. Exosomes have gained widespread attention as excellent drug delivery carriers with therapeutic potential. Tumor-derived exosomes, owing to their immunosuppressive properties, hold promise for immune regulation and may positively impact the treatment of RA. This study presents a delivery system using a cartilage matrix hyaluronic acid-chondroitin sulfate hydrogel (HC hydrogel) loaded with methotrexate-loaded osteosarcoma-derived exosomes (Exo@MTX). The injectable self-healing HC hydrogel, along with the exosomes, enables sustained release of MTX via local injection, reducing the frequency of administration and minimizing side effects. Furthermore, the system components work synergistically, not only providing immune regulation and anti-inflammatory effects by scavenging reactive oxygen species (ROS) and modulating macrophage M2 polarization but also protecting chondrocytes and promoting joint cartilage repair. Overall, this system integrates anti-inflammatory, immunoregulatory, and cartilage repair effects, demonstrating excellent therapeutic efficacy in a collagen-induced arthritis (CIA) rat model. It offers a potential therapeutic strategy leveraging tumor-derived exosome-mediated immunosuppressive effects, presenting a significant stride in RA treatment strategies.

Osteoarthritis, affecting millions globally each year, results in progressive joint function deterioration. The key to osteoarthritis treatment is the repair of damaged cartilage, while cartilage is poor at self-regeneration. Although autologous and allogeneic cartilage implantations are currently used to treat cartilage injuries, their clinical application is constrained by poor biocompatibility and limited donor availability. Tissue-engineered scaffolds have emerged as a promising strategy for cartilage repair, but their clinical translation is often limited by inadequate chondrogenic differentiation and inflammation control. In this study, we fabricated a biomimetic gelatin/graphene oxide (GO) composite cryogel scaffold for cartilage regeneration applications. This cryogel combines the advantages of gelatin and graphene oxide, exhibiting excellent mechanical properties, biocompatibility, and cell adhesion capacity while inducing chondrogenesis. After being implanted in a rat cartilage defect model, this cryogel effectively promoted structural and functional cartilage repair within 4 weeks. Furthermore, we investigated the underlying regenerative mechanism and demonstrated that this cryogel promotes cartilage regeneration by inducing chondrogenesis and suppressing oxidative phosphorylation. Collectively, these findings demonstrate that this cryogel represents a promising therapeutic approach for osteoarthritis resulting from cartilage injury.

Osteoarthritis (OA) is the most common chronic joint disease worldwide. Increasing studies have confirmed that obesity, metabolic status and gut microbiota imbalance can promote the occurrence of OA through the “metabolism-inflammation-oxidative stress” network, which is closely related to daily nutrition or dietary intake. The key nutrients with therapeutic effects mainly exert anti-inflammatory, anti-oxidative and chondro-protective effects. Among them, ω -3 polyunsaturated fatty acids and polyphenols are important components of anti-inflammatory diets, while collagen peptides, vitamin D, calcium, probiotics, glucosamine, chondroitin and hyaluronic acid are commonly used in clinical practice as important nutritional support treatments or preventive measures for OA to promote cartilage repair. In terms of dietary patterns, the Mediterranean diet (MD) rich in various nutrients can be used as the basic pattern for OA patients due to its anti-inflammatory and anti-oxidative properties and good clinical effects. Based on MD and evidence from clinical studies, this review constructs a four-level progressive nutritional plan for OA patients with the goals of relieving pain, delaying cartilage degeneration, improving function, and reducing the need for drugs and surgical intervention. We have also proposed customized nutritional management strategies for several special OA populations to reduce the occurrence of nutrition-related adverse events. Collectively, systematic nutritional intervention is expected to become the third major treatment alongside physical and drug therapy, enabling more OA patients to avoid adverse effects caused by repeated drug use and potential risks associated with surgery and prosthesis replacement.

BACKGROUNDOsteoarthritis (OA) remains a challenging degenerative joint disease with limited therapeutic interventions.AIMTo investigate the potential of synovial mesenchymal stem cell (SMSC)-derived exosomes (SMSCs-Exos) delivering GrpE-like 1 (GRPEL1) in promoting cartilage repair through phosphatase and tensin homolog-induced putative kinase 1 (PINK1)-mediated mitophagy activation.METHODSA comprehensive research approach was employed, including bioinformatics analysis of gene expression datasets (GSE169077 and GSE114007), in vitro experiments with CHON-001 chondrocytes, and in vivo rat knee OA models. Experimental techniques encompassed gene expression profiling, immunofluorescence staining, western blot analysis, co-immunoprecipitation, cell proliferation and migration assays, and histological examinations. Exosomes were genetically modified to overexpress or knockdown GRPEL1, and their effects on cellular function and mitochondrial dynamics were systematically evaluated.RESULTSBioinformatics analysis revealed GRPEL1 as a critical mitophagy-related gene with significantly altered expression in OA. In vitro studies demonstrated that GRPEL1-loaded SMSCs-Exos effectively counteracted interleukin-1 beta-induced cellular damage by enhancing chondrocyte proliferation and migration, preserving extracellular matrix integrity. Mechanistic investigations confirmed direct interaction between GRPEL1 and PINK1, leading to enhanced mitophagy activation. In vivo rat models substantiated these findings, showing significantly reduced cartilage damage, restored proteoglycan content, and improved joint structure in groups receiving GRPEL1-overexpressing exosomes. Key molecular changes included decreased reactive oxygen species, improved mitochondrial membrane potential, and increased mitophagy markers.CONCLUSIONThis study provides compelling evidence that SMSCs-Exos delivering GRPEL1 can effectively activate PINK1-mediated mitophagy, offering a promising therapeutic strategy for cartilage repair in OA. The research unveils a novel molecular mechanism for targeting mitochondrial dysfunction and presents a potential disease-modifying approach beyond current symptomatic treatments.

Talus osteoarthritis (OA) is a disabling condition that negatively affects the lives of individuals in terms of pain, functional limitation. Hydrogels, due to their viscoelastic, bioactive, and biocompatible properties, have emerged as a promising therapeutic option in cartilage repair and OA management. Currently hydrogel applications in other joint OA such as knee are extensively studied, while their use in talocrural joint degeneration remains underexplored. This systematic review aims to analyze the uncertainty in the effectiveness and safety of hydrogel-based therapies in the treatment of talus OA. Following PRISMA guidelines, a systematic search was conducted across PubMed, Embase, Scopus, Web of Science, and the Cochrane Library from 2015 up to 2025. Eligible studies included case series, cohort and randomized clinical trials investigating hydrogel implementation for talus OA. Data extraction and risk of bias assessments were independently performed by two reviewers. Thematic synthesis was applied due to heterogeneity in study designs. Preliminary screening identified 5 relevant studies. Hydrogel types included hyaluronic acid derivatives. Outcomes assessed included pain scores, joint function and imaging-based structural changes. Hydrogel-based therapies represent a promising joint-preserving option for talus osteoarthritis, offering potential cartilage support and symptom relief. However, current evidence remains limited. Larger, well-designed clinical trials with standardized outcome measures are essential to validate efficacy and refine formulations tailored to the unique biomechanics of the ankle joint.

Osteoarthritis (OA) is the most common joint disorder globally, affecting approximately 595 million individuals and representing the first cause of chronic pain and disability. Recently, the infrapatellar fat pad (IFP), an intracapsular adipose tissue in the human knee joint, was recognized as an active and metabolically significant contributor to the pathophysiology of OA through the release of pro-inflammatory cytokines, adipokines, and growth factors that sustain inflammatory response, fibrotic remodeling, and neurogenic pain. The present review provides an overview of the pathophysiological significance of the IFP in OA and current and promising therapeutic strategies targeting this adipose structure. We summarize the available preclinical and translational evidence on conservative therapies, minimally invasive interventions, and surgical options as well as IFP-derived mesenchymal stromal cells as a potential cell source for cartilage repair. Overall, preclinical research indicates that the modulation of IFP inflammation and fibrosis could alleviate pain and delay the progression of the disease. The superficial location and its central role in the pathogenesis of OA make the IFP a promising therapeutic target in knee OA (KOA).

The scaffold-free approach has emerged with a focus on creating cartilage-like tissues using cell pellets, cell spheroids, and cell sheets. However, complete repair of damaged cartilage using these tissues remains an ongoing challenge due to the limitation of thin structure and poor structural integrity. In this study, we proposed a novel method to produce scaffold-free cartilage by combining cell pellets and cell sheet technology as chondrocyte pellet-sheet tissues. The chondrocyte sheets acted as a support platform at the top and the bottom of the ten chondrocyte pellets. At day 7, the quality of the tissues cultured in a chondrogenic differentiation medium (CDM) and basal medium was compared using real-time PCR, immunofluorescence staining, proteomics, and atomic force microscopy (AFM). Our method supported the enhancement of tissue thickness. Compared to the control basal medium, the diameter and thickness of the chondrocyte pellet-sheet tissues in CDM were 1.47- and 2.21-fold increase, respectively. The level of mRNA expression and immunostaining of collagen type II were higher in the tissues cultured in CDM, compared to those in basal medium. Using proteomics, transferrin was found in both fresh and cultured CDM. The protein profiles of the tissues in CDM revealed the downregulation of actin and the upregulation of fibromodulin (FMOD), which related to the reorganization of cell shape and the production of cartilage ECM, respectively. Pathway analysis of chondrocyte pellet-sheet tissues in CDM also revealed the inhibition of RhoA and the presence of a TGFβ signaling pathway with SMAD protein signals. Moreover, Young's modulus indicating structural integrity of the tissues cultured in CDM (28.25 ± 13.13kPa) was higher than those in basal medium (4.63 ± 2.25kPa). Combining chondrocyte pellets and sheets in CDM allowed the generation of thick tissues and enhanced structural integrity. The compacted structure of the tissues in CDM might inhibit actin expression via RhoA inhibition. Growth factors in CDM, especially transferrin might be involved in chondrogenic differentiation via TGFβ signaling pathway with SMAD protein signals.

PDGF-BB inhibits F-actin formation and chondrocyte dedifferentiation in osteoarthritis via oxygen-dependent HIF-1α/SCIN regulation and RhoA/ROCK signaling inhibition.

Type II collagen (Col2), a crucial structural protein in hyaline cartilage, is essential for cartilage integrity and facilitating injury repair. However, research on recombinant type II collagen still faces many challenges, such as structure and yield, which limit the application of recombinant Col2 in biomedical fields. In this study, we achieved high-yield expression of full-length human Col2 (rhCol2) in CHO cells. The physical and chemical properties of rhCol2 were very close to native Col2, including molecular weight, triple helix structure, thermal stability and self-assembly capacity. Functional assays of primary chondrocytes have demonstrated that rhCol2 can effectively promote chondrocyte proliferation and increase the expression levels of cartilage-specific genes (Col2a1, Aggrecan, and Sox-9). Moreover, a cartilage defect model was surgically created in SD rats demonstrated that rhCol2 significantly enhanced cartilage repair, and the severity of the defect was assessed through histological and micro-CT analyses. Human chondrocytes were utilized to compare the effects of different collagens and verified through a series of functional experiments. In conclusion, these findings indicate that rhCol2 is an effective biomaterial and is expected to promote the application of recombinant collagen in the field of cartilage repair.