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OBJECTIVE: Realignment osteotomy performed concomitantly with cartilage restoration typically requires early restricted weightbearing and can add significant morbidity, potentially leading to an increased risk of early perioperative complications. The purpose of this study was to compare the 30-day complication rates after isolated cartilage restoration (ICR) versus concomitant cartilage restoration and osteotomy (CRO) using the American College of Surgeons National Surgical Quality Improvement Program (ACS-NSQIP) database. DESIGN: NSQIP registries between 2006 and 2019 were queried using Current Procedural Terminology codes to identify patients undergoing ICR (autologous chondrocyte implantation, osteochondral autograft transfer, or osteochondral allograft transplantation) and CRO (with concomitant high tibial osteotomy, distal femoral osteotomy, and/or tibial tubercle osteotomy). Complications rates between treatment groups were compared using multivariate logistic regression analyses adjusted for sex, age, steroid use, and respiratory status. RESULTS: A total of 773 ICR and 97 CRO surgical procedures were identified. Mean patient ages were 35.9 years for the ICR group and 31.2 years for the CRO group. Operative time was significantly longer in the CRO group (170.8 min) compared with the ICR group (97.8 min). Multivariate analysis demonstrated no significant differences in rates of PE, VTE, and all-cause readmission between the ICR and CRO groups. No events of wound disruption, SSI and reoperation were found in the CRO group, while the ICR group was characterized by low rates of wound disruption, reoperation, and SSI (

Objective: To systematically review the clinical efficacy and safety of high tibial osteotomy (HTO) combined with platelet-rich plasma (PRP) for treating knee osteoarthritis (KOA) and to provide evidence of the effectiveness of evidence-based medicine for treating this disease. Methods: Clinical studies on the use of HTO combined with PRP for the treatment of KOA before September 2024 were identified. The literature that met the inclusion criteria was strictly screened out, the literature information was extracted, and the data were input into RevMan5.4 for analysis. Results: Ten studies (12 controls) with 625 patients were included. Overall, the visual analog scale (VAS) score (mean difference (MD) = -0.53, 95% confidence interval (CI) (-0.76, -0.31), P < 0.00001), range of motion (ROM) (MD = 7.24, 95% CI (2.79, 11.69), P = 0.001), Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) score (MD = -6.91, 95% CI (-9.47, -4.34), P < 0.00001), cartilage recovery (cartilage thickness: MD = 0.43, 95% CI (0.35, 0.51), P < 0.00001; cartilage regeneration: relative risk (RR) = 1.81, 95% CI (1.40, 2.33), P < 0.00001; and the International Cartilage Repair Society (ICRS) grade: RR = 1.96, 95% CI (1.44, 2.66), P < 0.0001), and the Lysholm score (MD = 6.51, 95% CI (4.97, 8.04), P < 0.00001) after HTO-PRP treatment had certain advantages compared to the control group. After treatment, there was no statistically significant difference in the knee joint mechanical axis angle between the HTO-PRP group and the control group (femoral tibial angle (FTA): MD = -0.29, 95% CI (-1.07, 0.49), P = 0.47; medial proximal tibial angle (MPTA): MD = 0.19, 95% CI (-0.49, 0.88), P = 0.58; posterior tibial slope (PTS): MD = -0.12, 95% CI (-0.49, 0.25), P = 0.53; knee varus angle (KVA): MD = -0.30, 95% CI (-1.77, 1.17), P = 0.69; weight-bearing line (WBL): MD = 1.10, 95% CI (-0.89, 3.09), P = 0.28). Conclusion: The results showed that in the treatment of KOA, the HTO-PRP group had better efficacy than the control groups did and had certain safety reliability. [ABSTRACT FROM AUTHOR]

Osteoarthritis is a common degenerative disease characterized by continuous detachment of lubrication factors from damaged cartilage matrix. This study proposes a paradigm that combines natural polyanionic polysaccharides (hyaluronic acid, HA) with dopamine (DA) to design a synovial lubrication factors‐recruiting biomimetic polyphenolized lubrication system. The biomimetic lubricants can use DA's polarity and hydrophilic groups as specific binding sites of type II collagen's polarity and hydrophilic groups to stably bind cartilage surface, and further utilize molecular specific interaction to recruit detached, joint endogenous or chondrocytes expressed synovial lubrication factors, continuously forming supramolecular lubrication complex onto cartilage matrix to induce joint lubrication. Simultaneously, the biolubricants can also utilize catechol groups to eliminate anionic free radicals and resist reactive oxygen species invasion in the early stages of joint lubrication failure. The prepared biolubricants exhibit low coefficient of friction (µ < 0.08), which is attributed to fluid and hydration lubrication provided by HA and DA side chains through fluid dynamic effect and interfacial hydration adsorption. Cell and animal experiments also demonstrate polyphenolic biolubricants have good biocompatibility and promote cartilage regeneration. Therefore, the developed synovial lubricants‐recruiting biomimetic polyphenolized biolubricants have potential for treating osteoarthritis, and also provide a theoretical basis for other biological tissues with lubrication problems. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

To confirm the protective mechanism of genistein on osteoarthritis (OA). Firstly, we constructed an anterior cruciate ligament transection (ACLT) rat model and administered two doses of genistein via gavage. The effects of the drug on cartilage damage repair and synovitis in OA rats were evaluated through pain-related behavioral assessments, pathological staining, detection of inflammatory factors, and western blot analysis. Secondly, we constructed IL-1-induced chondrocytes and synovial fibroblast models, co-incubated them with genistein, and evaluated the protective effects of genistein on both types of cells through cell apoptosis and cytoskeleton staining. To verify the role of this pathway, we applied the GSK3β inhibitor TWS119 and the Wnt/β-catenin inhibitor XAV939 to ACLT rats and two types of cells to analyze the potential mechanism of genistein's action on OA. Our results confirmed the protective effect of genistein on joint cartilage injury in ACLT rats and its alleviating effect on synovitis. The results of cell experiments showed that genistein can protect IL-1β-induced chondrocytes and synovial fibroblasts, inhibit IL-1β-induced cell apoptosis, increase the fluorescence intensity of F-actin, and inhibit inflammatory response. The results of in vivo and in vitro mechanism studies indicated that TWS119 and XAV939 can attenuate the protective effects of genistein on OA rats and IL-1-induced cell damage. Our research confirmed that genistein may be an effective drug for treating osteoarthritis. Furthermore, we discussed and confirmed that the GSK3β/Wnt/β-catenin axis serves as a downstream signaling pathway of genistein, providing theoretical support for its application. [ABSTRACT FROM AUTHOR]

Introduction: Since 3D printing can be used to design implants according to the specific conditions of patients, it has become an emerging technology in tissue engineering and regenerative medicine. How to improve the mechanical, elastic and adhesion properties of 3D-printed photocrosslinked hydrogels is the focus of cartilage tissue repair and reconstruction research. Materials and Methods: We established a strategy for toughening hydrogels by mixing GelMA-DOPA (GD), which is prepared by coupling dopamine (DA) with GelMA, with HAMA, bacterial cellulose (BC) to produce composite hydrogels (HB–GD). HB–GD hydrogel scaffolds were characterized in vitro by scanning electron microscopy (SEM), Young's modulus, swelling property and rheological property tests. And biocompatibility and chondrogenic ability were tested by live/dead staining, DNA quantitative analysis and immunofluorescence staining. Combined with 3D bioprinting technology, mouse chondrocytes (ADTC5) were added to form a biological chain to construct an in vitro model, and the feasibility of the model for nasal cartilage regeneration was verified by cytology evaluation. Results: With the increase of GD concentration, the toughness of the composite hydrogel increased (47.0 ± 2.7 kPa (HB–5GD)–158 ± 3.2 kPa (HB–20GD)), and it had excellent swelling properties, rheological properties and printing properties. The HB–GD composite hydrogel promoted the proliferation and differentiation of ATDC5. Cells in 3D printed scaffolds had higher survival rates (> 95%) and better protein expression than the encapsulated cultures. Conclusion: The HB–10GD hydrogel can be made into a porous scaffold with precise shape, good internal pore structure, high mechanical strength and good swelling rate through extrusion 3D printing. No Level Assigned: This journal requires that authors assign a level of evidence to each submission to which Evidence-Based Medicine rankings are applicable. This excludes Review Articles, Book Reviews, and manuscripts that concern Basic Science, Animal Studies, Cadaver Studies, and Experimental Studies. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Purpose: To compare short‐term patient‐reported outcomes (PRO) of two contemporary matrix‐associated autologous chondrocyte implantation (M‐ACI) products for the treatment of large articular cartilage defects of the knee. Methods: A retrospective, registry‐based, matched‐pair analysis was performed, comparing PRO of patients undergoing isolated M‐ACI with either Spherox™, a spheroid‐based ACI (Sb‐ACI), or NOVOCART™ Inject, a hydrogel‐based ACI product (Hb‐ACI), for a focal full‐thickness cartilage defect of the knee ≥4 cm2. Matching parameters included age, sex, body mass index, defect size, defect localization, symptom duration and previous surgeries. The Knee Injury and Osteoarthritis Outcome Score (KOOS) and the International Knee Documentation Committee (IKDC) score were obtained up to the 24‐month follow‐up. The total KOOS response rate and percentage of patients attaining a substantial clinical benefit (SCB) in KOOS subscores were calculated. Results: A total of 45 patients per group were matched. The response rate after 24 months was not significantly different between the groups (Sb‐ACI 64.4% vs. Hb‐ACI 82.2%, p = 0.057). The number of patients with a SCB at 24 months was not significantly different in any KOOS subscore, despite significantly higher improvement of the total KOOS (14.8 ± 16.2 vs. 21.5 ± 15.4, p = 0.047) and KOOS pain in the Hb‐ACI group (12.2 ± 18.6 vs. 20.6 ± 19.1, p = 0.037). The IKDC score in the Hb‐ACI group was significantly higher at the 12‐ and 24‐month follow‐up (60.7 ± 20.2 vs. 70.9 ± 18.0, p = 0.013). Conclusion: The response rate and number of patients achieving an SCB were not significantly different between patients treated with Sb‐ACI or Hb‐ACI. Both procedures can achieve favourable 2‐year PRO. Hb‐ACI was associated with better PRO between 1 and 2 years postoperatively; however, the clinical relevance of this benefit is yet to be proven. Level of Evidence: III, Retrospective comparative study. [ABSTRACT FROM AUTHOR]

Abstract Objective To systematically review the clinical efficacy and safety of high tibial osteotomy (HTO) combined with platelet-rich plasma (PRP) for treating knee osteoarthritis (KOA) and to provide evidence of the effectiveness of evidence-based medicine for treating this disease. Methods Clinical studies on the use of HTO combined with PRP for the treatment of KOA before September 2024 were identified. The literature that met the inclusion criteria was strictly screened out, the literature information was extracted, and the data were input into RevMan5.4 for analysis. Results Ten studies (12 controls) with 625 patients were included. Overall, the visual analog scale (VAS) score (mean difference (MD) = -0.53, 95% confidence interval (CI) (-0.76, -0.31), P

Irregular articular cartilage injury is a common type of joint trauma, often resulting from intense impacts and other factors that lead to irregularly shaped wounds, the limited regenerative capacity of cartilage and the mismatched shape of the scaffods have contributed to unsatisfactory therapeutic outcomes. While injectable materials are a traditional solution to adapt to irregular cartilage defects, they have limitations, and injectable materials often lack the porous microstructures favorable for the rapid proliferation of cartilage cells. In this study, an injectable porous polyurethane scaffold named PU-BDO-Gelatin-Foam (PUBGF) was prepared. After injection into cartilage defects, PUBGF forms in situ at the site of the defect and exhibits a dynamic microstructure during the initial two weeks. This dynamic microstructure endows the scaffold with the ability to retain substances within its interior, thereby enhancing its capacity to promote chondrogenesis. Furthermore, the chondral repair efficacy of PUBGF was validated by directly injecting it into rat articular cartilage injury sites. The injectable PUBGF scaffold demonstrates a superior potential for promoting the repair of cartilage defects when compared to traditional porous polyurethane scaffolds. The substance retention ability of this injectable porous scaffold makes it a promising option for clinical applications.

BACKGROUND: Exosomes derived from mesenchymal stem cells are prospective cell-free alternatives for treating osteoarthritis. Their therapeutic activity and clinical transformation potential can be further improved by adjusting cell culture condition. OBJECTIVE: To review the effect of cell culture conditions on exosome activity and to analyze its clinical transformation potential. METHODS: Articles concerning osteoarthritis/cartilage repair and mesenchymal stem cell-derived exosomes were retrieved on CNKI and PubMed using “exosomes, mesenchymal stem cells, osteoarthritis or cartilage repair” as Chinese search terms and “exosomes or extracellular vesicles, mesenchymal stem cells, osteoarthritis or cartilage repair” as English search terms. The search time was from 2010 to 2023. Finally, 100 articles were included for summary and analysis. RESULTS AND CONCLUSION: (1) During cell culture, providing a physical environment favorable for chondrocyte growth or adding chondroprotective small molecules, chondrogenic factors, or inflammatory factors, can further improve the regulatory activity of exosomes secreted by mesenchymal stem cells in maintaining chondrocyte phenotype, promoting cartilage regeneration, and immunosuppression. Therefore, other physical or chemical factors with similar characteristics may also improve the effects of exosomes secreted by mesenchymal stem cells for treating osteoarthritis. (2) Some treatments during cell culture, such as hypoxia induction, pulsed electromagnetic field stimulation, bioreactor, and chondroprotective molecule (e.g., human parathyroid hormone 1-34) stimulation are safe and scalable, which allows for the production of clinical-grade exosomes secreted by mesenchymal stem cells for osteoarthritis treatment. (3) Mesenchymal stem cell exosomes are expected to achieve modified treatment of osteoarthritis, and the feasibility of clinical transformation can be further improved by adjusting the cell culture regimen to enhance the therapeutic activity. [ABSTRACT FROM AUTHOR]

BACKGROUND: Osteoarthritis is one of the most common senile chronic degenerative diseases in China. Due to its complex pathogenesis and cellular molecular communication pathways, there is currently no effective method to slow down the progression of osteoarthritis. Studies have found that transforming growth factor-β is one of the key factors in the maintenance and regulation of joint stability and plays a significant role in the formation of early joints, as well as the development of bone and cartilage, and the remodeling of joints at various stages. OBJECTIVE: To review the regulatory role of the transforming growth factor-β subfamily in the occurrence and development of osteoarthritis, both domestically and internationally in recent years, to analyze the impacts it has at different stages of osteoarthritis, and to explore the potential application prospects of transforming growth factor-β in the clinical treatment of osteoarthritis, with a view to informing clinical treatment protocols.. METHODS: The relevant articles were searched by computer from CNKI Database and PubMed Database. The search terms were “osteoarthritis, transforming growth factor, signaling pathway, bone remodeling, cartilage degeneration, angiogenesis, treatment” in Chinese and English, respectively. Finally, 57 articles were included for review. RESULTS AND CONCLUSION: The pathogenesis of osteoarthritis remains a subject of ongoing exploration with no unified consensus. Numerous studies highlight the close correlation between osteoarthritis and cytokines, focusing on the transforming growth factor-β superfamily as a pivotal mechanism and therapeutic breakthrough. Transforming growth factor-β plays a crucial role in early joint cartilage formation and maintenance, promoting cartilage repair. However, post-joint formation, its protective effect weakens, leading to potential destructive consequences. This dual regulatory role is a current clinical treatment focus, necessitating further research to delineate its application scope for standardized protocols. Highly active transforming growth factor-β participates in the regulation of bone cells, osteoblasts, and osteoclasts under mechanical stress, and intervenes in the subsequent remodeling of bone microstructure. Specific inhibitors present potential targeted therapeutics, yet their safety and efficacy in clinical settings require refinement. Vascular proliferation may serve as a potential disruptive pathway in transforming growth factor-β-mediated cartilage degeneration and subchondral bone remodeling. Abnormal communication pathways can further disrupt the homeostasis of the microenvironment of osteochondral units, thereby accelerating key pathological progressions of osteoarthritis. Research on transforming growth factor-β in osteoarthritic contexts is comprehensive, holding broad clinical application prospects. Drugs related to transforming growth factor-β are in clinical trial phases, but addressing potential impacts on other tissues and precise control of targeted delivery are critical concerns. As research advances, there is optimism for innovative breakthroughs in slowing the progression of osteoarthritis in the future. [ABSTRACT FROM AUTHOR]

BACKGROUND: Laser therapy is a non-invasive and painless treatment that is considered to be an effective method suitable for the treatment of osteoarthritis due to its simplicity and non-invasive nature. Currently, the mechanism of action of laser therapy is unclear and the results of studies on its clinical application are controversial. OBJECTIVE: To review and summarize the latest research progress of laser therapy on chondrocytes, animal experiments and clinical efficacy, and to explore the possible mechanism of laser-mediated multi-pathway biological effects, so as to provide a theoretical basis for further research on the laser treatment of osteoarthritis of the knee joint. METHODS: A literature search was performed in CNKI, WanFang Data, VIP and PubMed databases for relevant literature published from 2018 to 2023, with “laser therapy, low level laser therapy, high level laser therapy, photobiomodulation, knee osteoarthritis, chondrocytes” as the search terms in Chinese and English, respectively. Together with 14 articles searched manually, 70 articles were finally included for review. RESULTS AND CONCLUSION: Laser therapy in the treatment of knee osteoarthritis is mainly categorized into two types: low-level laser therapy and highlevel laser therapy. Differences in laser parameters and treatment protocols have a direct impact on laser efficacy. When appropriate parameters are used, low-level lasers show positive effects in cellular experiments, animal models, and clinical efficacy. High-level lasers have been less studied in the treatment of knee osteoarthritis, but some preliminary clinical studies have shown positive results. Cell experiments have shown that low-level laser promotes chondrocyte proliferation and cartilage matrix synthesis, thereby reducing inflammatory response. Animal experiments have shown that low-level laser can reduce the release of pro-inflammatory factors, promote cartilage matrix synthesis, inhibit matrix degradation, and effectively improve the repair process of cartilage tissue. Low-level laser is also able to reduce oxidative stress damage and relieve pain in knee osteoarthritis. In clinical trials, both low- and high-level laser can reduce patients’ pain and improve functional activities. The combination of laser therapy and exercise therapy modalities may improve the therapeutic effect. Lasers may affect intracellular signaling and cellular functions through photobiological or thermodynamic effects. This provides direct evidence that laser promotes articular cartilage regeneration. [ABSTRACT FROM AUTHOR]

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-1β. 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-1β-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. [ABSTRACT FROM AUTHOR]

Treatments for articular cartilage injuries are still challenging, due in part to its avascular and aneural surroundings. Since the first report of autologous chondrocyte implantation, cell-based therapies have been extensively studied with a variety of cell sources, including chondrocytes and mesenchymal stem/stromal cells (MSCs). Recently, MSC-based therapy has received considerable research attention because of the relative ease in handling for tissue harvest, and subsequent cell expansion and differentiation. Using such cells, we have originally developed a 3-dimensional scaffold-free tissue-engineered construct (TEC) through simple-cell culture methods and demonstrated its feasibility for cartilage repair and regeneration in the first-in-human clinical trial. This review summarizes our novel scaffold-free approaches to use MSC for the restoration of damaged articular cartilage, documenting the progression from basic to clinical studies.

Osteoarthritis (OA) is a degenerative disease caused by a variety of factors with joint pain as the main symptom, including fibrosis, chapping, ulcers, and loss of cartilage. Traditional treatment can only delay the progression of OA, and classical delivery system have many side effects. In recent years, microspheres have shown great application prospects in the field of OA treatment. Microspheres can support cells, reproduce the natural tissue microenvironment in vitro and in vivo, and are an efficient delivery system for the release of drugs or biological agents, which can promote cell proliferation, migration, and differentiation. Thus, they have been widely used in cartilage repair and regeneration. In this review, preparation processes, basic materials, and functional characteristics of various microspheres commonly used in OA treatment are systematically reviewed. Then it is introduced surface modification strategies that can improve the biological properties of microspheres and discussed a series of applications of microsphere functionalized scaffolds in OA treatment. Finally, based on bibliometrics research, the research development, future potential, and possible research hotspots of microspheres in the field of OA therapy is systematically and dynamically evaluated. The comprehensive and systematic review will bring new understanding to the field of microsphere treatment of OA. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

To explore the ability of three-dimensional texture analyses based on gray-level run-length matrix (GLRLM) for examining the spatial distribution of pixel values on magnetic resonance imaging (MRI) relaxation time maps and detecting the compositional variation of cartilage repair following treatment with allogeneic human adipose-derived mesenchymal progenitor cells (haMPCs). Participants with knee osteoarthritis were randomly divided into three groups with intra-articular haMPCs injections: low-, medium-, and high-dose groups. We analyzed five GLRLM parameters in the T1rho, T2 and T2star maps, including run length non-uniformity (RLNonUni), gray-level non-uniformity (GLevNonU), long run emphasis (LngREmph), short run emphasis (ShrtREmp), and fraction of images in runs. We used the relative D values (the ratio of difference values to baseline) as the objective to avoid errors caused by individual differences. We calculated the two-tailed Pearson's linear correlation coefficient (r) to investigate the correlations of the texture parameters with the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) scores. Compared with the base time, significant reduction of WOMAC score was observed in both high and medium doses groups at terminal time, indicating relief of pain symptoms in high and medium groups with the treatment of allogeneic haMPCs. Significant differences were observed in the GLRLM parameters of cartilage MR relaxation time maps in different doses groups. In both T1rho and T2 relaxation time maps, the high-dose group showed significant increases in relative D values of RLNonUni, GLevNonU, LngREmph and ShrtREmp, which indicated significant changes in the uniformity of relaxation time maps. For T2star map, GLRLM parameters such as GLevNonU and ShrtREmp, especially LngREmph, showed significant increases in relative D values in high-dose group. Among all GLRLM features, LngREmph of three relaxation time maps had performed excellent linear correlations with WOMAC scores. Texture analysis of the cartilage may allow the detection of compositional variation in cartilage repair with the treatment of allogeneic haMPCs. This technique displays potential applications in understanding the mechanism of stem cell repair of the cartilage and assessing the treatment response. [ABSTRACT FROM AUTHOR]

Suitable hydrogel materials for cartilage tissue repair should exhibit high strength and toughness, and excellent biocompatibility. However, the mechanical properties of most hydrogels cannot meet the complex mechanical requirements of articular cartilage tissues. Given this situation, we have adopted a chemical cross-linking method using hexafluoro isopropanol to mediate the cross-linking of Silk Fibroin (SF) and deionized water (DI), which promoted the formation of ß-sheets, generating "high-toughness" Silk Fibroin hydrogels. The introduction of Gelatin (Gel) served to increase the content of ß-sheets and increase the tensile modulus from 24.51 ± 2.07 MPa to 39.75 ± 6.54 MPa, which significantly enhanced the flexibility of the hydrogel and meets the mechanical requirements of cartilage tissue. In addition, in vitro biological experiments have shown that the introduction of Gel promotes cell proliferation and enhances the production of cartilage extracellular matrix by chondrocytes. In vivo experiments have demonstrated that SF/Gel hydrogel promotes articular cartilage regeneration more effectively than SF hydrogel, as evidenced by improvements in gross appearance, imaging, and histology. This study has established that high-strength SF/Gel hydrogel prepared by applying the binarysolvent-induced conformation transition strategy has potential applications in cartilage tissue repair and regeneration and is a feasible biomaterial for osteochondral regeneration. [ABSTRACT FROM AUTHOR]

Articular cartilage lesions are a common injury that have become increasingly treatable with joint preservation procedures. Well-documented allograft and cellular treatments for these lesions are detailed elsewhere in this volume. This article discusses three new unique options for addressing these defects taking three different paths to address these complex injuries. Agili-C is an existing FDA- and EMEA-approved option using an acellular aragonitebased scaffold to treat both chondral and osteochondral lesions, with or without concurrent arthritis. Cartistem is a stem-cell-based product composed of culture-expanded allogeneic human umbilical cord blood-derived mesenchymal stem cells and hyaluronic acid hydrogel, which is in its final clinical trial stages in the United States, but already has regulatory approval in Korea. IMPACT and RECLAIM studies have shown the safety and efficacy of a new onestage procedure utilizing autologous chondrons combined with allogeneic mesenchymal stem cells (MSCs) that can provide another effective single-stage treatment option. [ABSTRACT FROM AUTHOR]

The case presentation describes a joint-preserving procedure for pre-existing focal cartilage damage to the shoulder joint with the onset of osteoarthritis in a young female patient with high sporting demands. A significant improvement in quality of life was achieved after an observation period of two years. Imaging morphology shows good cartilage regeneration in the PD sequences in the MRI after application of matrix-augmented bone marrow stimulation using a hyaluronic acid matrix. The clinical and morphological results offer hope for future success in delaying shoulder joint replacement. [ABSTRACT FROM AUTHOR]

General principles of cartilage repair therapies have not changed in the last years. Recommendations for cartilage repair include symptomatic ICRS grade 3 and 4 classified cartilage defects. However, what has changed in the last years is a better understanding of underlying or concomitant pathologies. Since a more precise analysis and stringent therapy of concomitant pathologies has been performed, an increase in success rates especially in formerly difficult entities could be observed. The most important concomitant pathologies in cartilage therapies of the hip-, knee- and ankle joint are axis deviations, instabilities, meniscus pathologies or prearthrotic deformities like hip dysplasia and femuroacetabular impingement syndrome. To increase the efficiency of cartilage repair procedures these pathologies should be corrected either prior to, or at latest concomitant to any cartilage repair surgery. Therefore, this article is intended to give an overview of the most important concomitant pathologies in cartilage repair of the lower extremities and their possibilities of correction. [ABSTRACT FROM AUTHOR]

Chondrocyte-based cell therapy has been used for more than 30 years and is still considered to be a promising method of cartilage repair despite some limitations. This review introduces the latest developments of four generations of autologous chondrocyte implantation and current autologous chondrocyte products. The regeneration of cartilage from adult chondrocytes is limited by culture-induced dedifferentiation and patient age. Cartibeads is an innovative three-step method to produce high-quality hyaline cartilage microtissues, and it is developed from adult dedifferentiated chondrocytes with a high number of cell passages. In addition, allogeneic chondrocyte therapies using the Quantum hollow-fiber bioreactor and several signaling pathways involved in chondrocyte-based cartilage repair are mentioned, such as WNT signaling, the BMP-2/WISP1 pathway, and the FGF19 pathway. [ABSTRACT FROM AUTHOR]

Background: Chondral defects in the knee present a significant challenge due to their limited self-healing capacity, often leading to joint degeneration and functional disability. Current treatments, including surgical approaches like mosaicplasty and regenerative therapies such as bone marrow aspirate concentrate (BMAC) augmentation, aim to address these defects and improve patient outcomes. Materials and Methods: This study conducted a single-center, randomized controlled trial to evaluate the efficacy of different treatment approaches and rehabilitation protocols for chondral defects. Thirty-seven subjects presenting with symptomatic chondral or osteochondral defects (>3 cm2) in the weight-bearing region of the femoral condyle were partitioned into three groups, and underwent mosaicplasty with or without BMAC augmentation, followed by either a 6-week or 12-week rehabilitation program. Group 1 (n = 10) received mosaicplasty combined with BMAC augmentation and engaged in a twelve-week two-phase rehabilitation protocol. Group 2 (n = 15) underwent mosaicplasty alone and participated in the same twelve-week two-phase rehabilitation regimen. Meanwhile, Group 3 (n = 12) underwent mosaicplasty and underwent a shorter six-week one-phase rehabilitation program. Clinical assessments were performed using the visual analog scale (VAS) for pain, goniometry for the knee's range of motion (ROM), manual muscle testing (MMT) for quadricep strength, and the Western Ontario and McMaster University Arthritis Index (WOMAC) for functional evaluation in three test phases. Results: Significant differences in WOMAC scale scores were observed between the three groups at the intermediate (F(2, 34) = 5.24, p < 0.010) and final (F(2, 34) = 111, p < 0.000) stages, with post hoc Tukey tests revealing variations shared among all three groups. The between-group analysis of the VAS scale demonstrated no statistically significant difference initially (F(2, 34) = 0.18, p < 0.982), but significant differences emerged following the intermediate (F(2, 34) = 11.40, p < 0.000) and final assessments (F(2, 34) = 59.87, p < 0.000), with post hoc Tukey tests revealing specific group variations, notably between Group 1 and both Group 2 and Group 3, and also between Group 3 and Group 2. The between-group analysis of quadricep muscle strength using MMT scores revealed no statistically significant differences initially (F(2, 34) = 0.376, p < 0.689) or following the intermediate assessment (F(2, 34) = 2.090, p < 0.139). The one-way ANOVA analysis showed no significant difference in the knee ROM initially (F(2, 34) = 1.037, p < 0.366), but significant differences emerged following intermediate (F(2, 34) = 9.38, p < 0.001) and final assessments (F(2, 34) = 11.60, p < 0.000). Post hoc Tukey tests revealed significant differences between Groups 1 and 2, Groups 1 and 3, and Groups 2 and 3 at intermediate and final assessments. Conclusions: The patients who received BMAC augmentation and completed a 12-week rehabilitation protocol had significantly better outcomes in pain relief, knee function, and ROM when compared to those who did not receive BMAC augmentation or those who completed a shorter rehabilitation period. Our findings suggest that combining mosaicplasty with BMAC augmentation and a comprehensive rehabilitation program can lead to superior clinical outcomes for patients with chondral defects in the knee. [ABSTRACT FROM AUTHOR]

Abstract From degeneration causing intervertebral disc issues to trauma‐induced meniscus tears, diverse factors can injure the different types of cartilage. This review highlights adhesives as a promising and rapidly implemented repair strategy. Compared to traditional techniques such as sutures and wires, adhesives offer several advantages. Importantly, they seamlessly connect with the injured tissue, deliver bioactive substances directly to the repair site, and potentially alleviate secondary problems like inflammation or degeneration. This review delves into the cutting‐edge advancements in adhesive technology, specifically focusing on their effectiveness in cartilage injury treatment and their underlying mechanisms. We begin by exploring the material characteristics of adhesives used in cartilage tissue, focusing on essential aspects like adhesion, biocompatibility, and degradability. Subsequently, we investigate the various types of adhesives currently employed in this context. Our discussion then moves to the unique role adhesives play in addressing different cartilage injuries. Finally, we acknowledge the challenges currently faced by this promising technology.

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.

Objective: This dextran-tyramine hydrogel is a novel cartilage repair technique, filling focal cartilage defects to provide a cell-free scaffold for subsequent cartilage repair. We aim to asses this techniques’ operative feasibility in the knee joint and its ability to maintain position and integrity under expected loading conditions. Method: Seven fresh-frozen human cadaver legs (age range 55–88) were used to create 30 cartilage defects on the medial and lateral femoral condyles dependent of cartilage quality, starting with 1.0 ​cm2; augmenting to 1.5 ​cm2 and eventually 2.0 ​cm2. The defects were operatively filled with the injectable hydrogel scaffold. The knees were subsequently placed on a continues passive motion machine for 30 ​min of non-load bearing movement, mimicking post-operative rehabilitation. High resolution digital photographs documented the hydrogel scaffold after placement and directly after movement. Three independent observers blinded for the moment compared the photographs on outline attachment, area coverage and hydrogel integrity. Results: The operative procedure was uncomplicated in all defects, application of the hydrogel was straightforward and comparable to common cartilage repair techniques. No macroscopic iatrogenic damage was observed. The hydrogel scaffold remained predominately unchanged after non-load bearing movement. Outline attachment, area coverage and hydrogel integrity were unaffected in 87%, 93% and 83% of defects respectively. Larger defects appear to be more affected than smaller defects, although not statistically significant (p ​> ​0.05). Conclusion: The results of this study show operative feasibility of this cell-free hydrogel scaffold for chondral defects of the knee joint. Sustained outline attachment, area coverage and hydrogel integrity were observed after non-load bearing knee movement.

Abstract Osteoarthritis (OA), known as one of the most common types of aseptic inflammation of the musculoskeletal system, is characterized by chronic pain and whole-joint lesions. With cellular and molecular changes including senescence, inflammatory alterations, and subsequent cartilage defects, OA eventually leads to a series of adverse outcomes such as pain and disability. CRISPR-Cas-related technology has been proposed and explored as a gene therapy, offering potential gene-editing tools that are in the spotlight. Considering the genetic and multigene regulatory mechanisms of OA, we systematically review current studies on CRISPR-Cas technology for improving OA in terms of senescence, inflammation, and cartilage damage and summarize various strategies for delivering CRISPR products, hoping to provide a new perspective for the treatment of OA by taking advantage of CRISPR technology.

Osteoarthritis (OA), a common degenerative disease, is characterized by high disability and imposes substantial economic impacts on individuals and society. Current clinical treatments remain inadequate for effectively managing OA. Organoids, miniature 3D tissue structures from directed differentiation of stem or progenitor cells, mimic native organ structures and functions. They are useful for drug testing and serve as active grafts for organ repair. However, organoid construction requires extracellular matrix-like 3D scaffolds for cellular growth. Hydrogel microspheres, with tunable physical and chemical properties, show promise in cartilage tissue engineering by replicating the natural microenvironment. Building on prior work on SF-DNA dual-network hydrogels for cartilage regeneration, we developed a novel RGD-SF-DNA hydrogel microsphere (RSD-MS) via a microfluidic system by integrating photopolymerization with self-assembly techniques and then modified with Pep-RGDfKA. The RSD-MSs exhibited uniform size, porous surface, and optimal swelling and degradation properties. In vitro studies demonstrated that RSD-MSs enhanced bone marrow mesenchymal stem cells (BMSCs) proliferation, adhesion, and chondrogenic differentiation. Transcriptomic analysis showed RSD-MSs induced chondrogenesis mainly through integrin-mediated adhesion pathways and glycosaminoglycan biosynthesis. Moreover, in vivo studies showed that seeding BMSCs onto RSD-MSs to create cartilage organoid precursors (COPs) significantly enhanced cartilage regeneration. In conclusion, RSD-MS was an ideal candidate for the construction and long-term cultivation of cartilage organoids, offering an innovative strategy and material choice for cartilage regeneration and tissue engineering.

Hydrogel is an ideal material for cartilage repair, but it is difficult for artificial materials to achieve ultra-low friction coefficient of cartilage at present. The amphoteric ion anionic double crosslinked P(AAm-co-AAc-co-SBMA-co-AMPS)/Fe3+hydrogel was synthesized by using the amphoteric monomer [2-(methacryloxy) ethyl] dimethyl-(3-sulfopropyl)(SBMA) and the anionic monomer 2-acrylamido-2-methylpropane sulfonic acid (AMPS). The frictional tests were conducted in water and PBS to evaluate the effects of zwitterionic and anionic groups on the coefficient of friction (CoF). The results show that the physical crosslinking point introduced by SBMA and AMPS can improve the compressive strength of hydrogel, and achieve a low CoF (0.04) in water, In addition, it is observed that CoF further decreases to 0.015 in PBS, and the decrease of CoF is caused by the highly hydrated upper layer of hydrogel produced during PBS soaking.

Articular cartilage (AC) has a poor capacity to repair once damaged, with progressive degeneration often leading to osteoarthritis (OA). While biomaterials fabricated with extra cellular matrix (ECM) native to the AC have shown promise for repair of focal AC defects, several challenges must be overcome for the repair of larger load bearing defects due to poor scaffold mechanical properties and a lack of chondrogenic potential in diseased cells. Here, we develop a method to improve such biomaterials by incorporating a bioabsorbable 3D printed reinforcing framework and the delivery of pro-chondrogenic genes to infiltrating stem cells to enhance chondrogenesis and produce hyaline tissue that is more indicative of healthy AC. A bioabsorbable polycaprolactone (PCL) 3D printed framework was surface treated to improve its hydrophilicity and used to reinforce a collagen hyaluronic acid (CHyA) matrix. The mechanically reinforced scaffolds were then gene-activated (GA) with the chondrogenic transcription factor SOX9 which was complexed with non-viral nanoparticles (NPs) generated using the glycosaminoglycan-binding enhanced transduction (GET) system, before being seeded with human mesenchymal stromal cells (hMSC). After 28 days culture in chondrogenic media, hMSCs on the GA-scaffolds deposited an ECM more indicative of healthy hyaline cartilage compared to the gene free control. SOX9 mRNA expression on the GA scaffold was 2-orders of magnitude higher than on the control, with downstream chondrogenic targets of SOX9 (COL2α1, ACAN) also expressing significantly higher mRNA levels. Expression of pro-chondrogenic ECM proteins such as COL2, were 17.5 times greater (p = 0.0018) on the GA scaffold which also resulted in enhanced production and spatial distribution of sulphated glycosaminoglycans (sGAG), which are critical to the function of healthy AC. In summary, these findings provide evidence that functionalization of a 3D printed biomimetic pro-chondrogenic scaffold with SOX9 NPs enhances the quality of ECM produced by human stem cells on such mechanically reinforced scaffolds.

Abstract Background Osteoarthritis OA is a common progressive disabling disease. Current research aims at finding therapies to prevent its progression. In this work, we assessed the therapeutic role of intra-articular injection of stromal vascular fraction SVF in collagenase induced knee OA in rats. Results Post right Knee OA induction in 42 Wistar rats, histopathological examination and quantification of articular cartilage degeneration using Mankin’s score revealed degenerative changes were significantly higher in untreated Group II compared to SVF treated Group III at 1 month (10.75 ± 0.50 and 2.50 ± 0.53, P = 0.001) and 2 months (8.50 ± 0.58, 0.50 ± 0.53, P = 0.001), respectively. Morphometric computerized image analysis revealed a significant difference between treated, untreated and healthy control group I regarding chondrocyte cellular count, articular cartilage thickness and optical density OD of the cartilage (P

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)-1β 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.

ABSTRACTMesenchymal stem cells (MSCs) with multipotential differentiation ability are main cell source for cartilage tissue engineering, but its application is restricted by the difficulty in regulating committed chondrogenic differentiation. Study revealed that certain substrate topographic structure can enhance the chondrogenic differentiation of MSCs. This study prepared silk fibroin (SF) films with gradient microscopic surface patterns based on P280-P7000 type specification sandpapers, and investigated the adhesion, proliferation and chondrogenic differentiation of human adipose-derived stem cells (hADSCs) on the SF films. The results showed that the SF films surface had convex dots with diameter of 3–50 μm, and hADSCs could adhere and proliferate well on the film. Transcriptomics analysis indicated that hADSCs tend to differentiate differently on the SF films, among which hADSCs on P1000 SF films had higher expression of chondrogenic markers Sox-9 and Col-II, with activated yes associated protein (YAP) and restricted F-actin. In vitro co-culture of human OA knee cartilage with hADSCs seeded SF films found satisfactory cartilage protection effect in P1000 group. Overall, this study preliminarily revealed the microscopic surface pattern of SF films may induce chondrogenic differentiation of hADSCs through extracellular matrix mediated Hippo/Yap pathway, and provided a new strategy for cartilage repair.

BACKGROUND: Nanocomposite hydrogel has great research prospects and application potential in the treatment of osteoarthritis. OBJECTIVE: To review the research progress of nanocomposite hydrogel in osteoarthritis and cartilage repair. METHODS: Databases such as CNKI and PubMed were searched. The English key words were “nanocomposite hydrogel, nanogel, osteoarthritis, cartage, physical encapsulation, electrostatic interaction, covalent crosslinking”, and the Chinese key words were “nanocomposite hydrogel, nanogel, osteoarthritis, cartage, physical encapsulation, physical encapsulation, electrostatic effect, covalent cross-linking”. After an initial screening of all articles based on inclusion and exclusion criteria, 71 articles with high correlation were retained for review. RESULTS AND CONCLUSION: In cell or animal experiments, nanocomposite hydrogel has the effect of improving osteoarthritis. Nanocomposite hydrogel can promote cartilage repair, improve the internal environment of osteoarthritis, and achieve the therapeutic purpose of osteoarthritis by improving the mechanical environment between joints, carrying targeted drugs, and promoting the chondrogenesis of seed cells. At present, the research of nanocomposite hydrogel in osteoarthritis disease still has a huge space to play. It is expected to open up a new way for the clinical treatment of osteoarthritis by continuing to deepen the research of material preparation and actively carrying out cell and animal experiments. [ABSTRACT FROM AUTHOR]

BACKGROUND: Scaffold materials serve as platforms that provide space and structure, playing a crucial role in the regeneration of cartilage tissue. Scholars from around the world are exploring different approaches to fabricate more ideal scaffold materials. OBJECTIVE: To review the design principles and preparation methods of cartilage scaffolds, and to further explore the advantages and limitations of various preparation methods. METHODS: Literature searches were conducted on the databases of CNKI, WanFang Data, PubMed, and FMRS from 1998 to 2023. The search terms were “cartilage repair, cartilage tissue engineering, cartilage scaffold materials, preparation” in Chinese and English. A total of 57 articles were ultimately reviewed. RESULTS AND CONCLUSION: (1) The articular cartilage has a unique structure and limited self-repair capacity after injury. Even if self-repair occurs, the newly formed cartilage is typically fibrocartilage, which is far inferior to normal articular cartilage in terms of structure and mechanical properties. It is difficult to maintain normal function and often leads to degenerative changes. Currently, the design and fabrication of scaffold materials for cartilage repair need to consider the following aspects: biocompatibility and biodegradability, suitable pore structure and porosity, appropriate mechanical properties, and bioactivity. (2) Research on the preparation of cartilage scaffolds has made significant progress, continuously introducing new preparation methods and optimization strategies. These methods have their advantages and disadvantages, providing more possibilities for customized preparation and functional design of cartilage scaffolds according to specific requirements. [ABSTRACT FROM AUTHOR]

BACKGROUND: Natural bone morphogenetic protein 2 disperses and degrades rapidly in vivo, reducing local concentration and therapeutic efficacy. Simply combining bone morphogenetic protein 2 with tissue engineering scaffolds could not stay in vivo for a long time, making it difficult to achieve good sustained and controlled release effects. OBJECTIVE: To prepare and test the biological properties and chondrogenic induction effect of collagen-binding domain-bone morphogenetic protein 2-collagen cartilage scaffold. METHODS: SD rat tail collagen was extracted and a collagen cartilage scaffold was prepared using a vacuum freeze-drying machine chemical crosslinking method. The plasmid expressing collagen-binding domain-bone morphogenetic protein 2 was constructed by rapid cloning C112 homologous recombination, constructed by genetic engineering, and introduced into E. coli, and then collagen-binding domain-bone morphogenetic protein 2 was isolated and purified. Natural bone morphogenetic protein 2 and collagen-binding domain-bone morphogenetic protein 2 were combined with collagen cartilage scaffolds, respectively, to detect the release level of bone morphogenetic protein 2 in the scaffolds. The biocompatibility of collagen-binding domain-bone morphogenetic protein 2-collagen cartilage scaffold was detected by CCK-8 assay and F-Actin staining. Bone marrow mesenchymal stem cells were implanted on two kinds of collagen cartilage scaffolds for chondrogenic induction, and their chondrogenic induction activity was tested. RESULTS AND CONCLUSION: (1) The binding rate of collagen-binding domain-bone morphogenetic protein 2 to collagen cartilage scaffolds was higher than that of natural bone morphogenetic protein 2 (P < 0.05). After being immersed in PBS for 7 days in vitro, the release of bone morphogenetic protein 2 in the collagen-binding domain bone morphogenetic protein 2-collagen cartilage scaffold was smaller than that in the natural bone morphogenetic protein 2-collagen cartilage scaffold (P < 0.05). The results of the CCK-8 assay and F-Actin staining showed that the collagen-binding domain-bone morphogenetic protein 2-collagen cartilage scaffold had no obvious cytotoxicity and had good biocompatibility. (2) After 14 days of chondrogenic induction, ELISA detection demonstrated that the expressions of agglutincan and type II collagen A1 in the collagen-binding domain-bone morphogenetic protein 2-collagen cartilage scaffold group were higher than those in the natural bone morphogenetic protein 2-collagen cartilage scaffold group (P < 0.05). Under scanning electron microscopy, more bone marrow mesenchymal stem cells were observed on the inner wall of the pores of the two groups of scaffolds, and the cell morphology and size were the same, and the cells were closely arranged, without cell fragmentation or abnormal morphology. (3) The results indicate that the collagen-binding domain-bone morphogenetic protein 2-collagen cartilage scaffold has good biological properties and chondrogenic induction activity. [ABSTRACT FROM AUTHOR]

Osteoarthritis (OA), known as one of the most common types of aseptic inflammation of the musculoskeletal system, is characterized by chronic pain and whole-joint lesions. With cellular and molecular changes including senescence, inflammatory alterations, and subsequent cartilage defects, OA eventually leads to a series of adverse outcomes such as pain and disability. CRISPR-Cas-related technology has been proposed and explored as a gene therapy, offering potential gene-editing tools that are in the spotlight. Considering the genetic and multigene regulatory mechanisms of OA, we systematically review current studies on CRISPR-Cas technology for improving OA in terms of senescence, inflammation, and cartilage damage and summarize various strategies for delivering CRISPR products, hoping to provide a new perspective for the treatment of OA by taking advantage of CRISPR technology. [ABSTRACT FROM AUTHOR]

Cartilage defects in the knee are often associated with the progression of degenerative osteoarthritis (OA), and cartilage repair is a useful strategy for managing this disease. However, cartilage repair is challenging because of the unique environment within the tissue. Recently, stem cell‐based therapies have shed new light on this issue. In this study, we prepared exosomes (EXOs) from cartilage stem/progenitor cells (CSPCs) and found that treatment with EXOs increased the viability, migration, and proliferation of cultured primary chondrocytes. In a subacute OA rat model, the application of EXOs facilitated cartilage regeneration as evidenced by histological staining. Exosomal protein analysis together with bioinformatics suggested that cyclin‐dependent kinase 9 (CDK9) is a key factor for chondrocyte growth and migration. Functional studies confirmed this prediction, that is, inhibiting CDK9 reduced the beneficial effects induced by EXOs in primary chondrocytes; while overexpression of CDK9 recapitulated the EXOs‐induced phenotypes. RNA‐Seq data showed that a set of genes involved in cell growth and migration were up‐regulated by EXOs in chondrocytes. These changes could be partially reproduced by CDK9 overexpression. Overall, our data suggest that EXOs derived from primary CSPCs hold great therapeutic potential for treating cartilage defect‐associated disorders such as degenerative OA, and that CDK9 is a key factor in this process. [ABSTRACT FROM AUTHOR]

Background: Marrow stimulation is a common reparative approach to treat injuries to cartilage and other soft tissues (e.g., rotator cuff). It involves the recruitment of bone marrow elements and mesenchymal stem cells (MSCs) into the defect, theoretically initiating a regenerative process. However, the resulting repair tissue is often weak and susceptible to deterioration with time. The populations of cells at the marrow stimulation site (beyond MSCs), and their contribution to inflammation, vascularity, and fibrosis, may play a role in quality of the repair tissue. Summary: In this review, we accomplish three goals: (1) systematically review clinical trials on the augmentation of marrow stimulation and evaluate their assumptions on the biological elements recruited; (2) detail the cellular populations in bone marrow and their impact on healing; and (3) highlight emerging technologies and approaches that could better guide these specific cell populations towards enhanced cartilage or soft tissue formation. Key Messages: We found that most clinical trials do not account for cell heterogeneity, nor do they specify the regenerative element recruited, and those that do typically utilize descriptions such as “clots,” “elements,” and “blood.” Furthermore, our review of bone marrow cell populations demonstrates a dramatically heterogenous cell population, including hematopoietic cells, immune cells, fibroblasts, macrophages, and only a small population of MSCs. Finally, the field has developed numerous innovative techniques to enhance the chondrogenic potential (and reduce the anti-regenerative impacts) of these various cell types. We hope this review will guide approaches that account for cellular heterogeneity and improve marrow stimulation techniques to treat chondral defects. [ABSTRACT FROM AUTHOR]

BACKGROUND: Cartilage degeneration and subchondral bone damage are the main pathological features of osteoarthritis, and treatment based on this pathological feature will be a promising improvement for osteoarthritis. OBJECTIVE: To design and study an annotated strontium ranelate-loaded drug delivery system and to observe its therapeutic effect on promoting cartilage repair and improving subchondral bone structure in osteoarthritis. METHODS: (1) In vitro experiment: Strontium ranelate was loaded into sodium alginate/collagen hydrogel matrix to construct in situ drug delivery system, and the in vitro slow release performance of the system was characterized. Strontium ranelate-loaded sodium alginate/collagen hydrogel (experimental group) and alginate sodium/collagen hydrogel (control group) were co-cultured with bone marrow mesenchymal stem cells, respectively, and cultured cells were used as a blank control group to detect cell proliferative activity. After chondroblast-induced differentiation, saffron O staining, Alcian blue staining and RT-qPCR were performed respectively. The two hydrogels were co-cultured with osteoblasts, and the cultured cells were used as a blank control group for immunofluorescence staining and RT-qPCR. (2) In vivo experiment: A total of 18 adult SD rats were selected and the model of right posterior knee osteoarthritis was established by the method of medial meniscectomy. After 1 week, the rats were divided into three groups by the random number table method: The blank group did not receive any treatment. The control group was injected with sodium alginate/collagen hydrogel in the knee, and the experimental group was injected with strontium ranelate-loaded sodium alginate/collagen hydrogel, with 6 rats in each group. After 6 weeks, the samples were subjected to Micro-CT scanning, hematoxylin-eosin staining, saffron O-solid green staining and immunofluorescence staining. RESULTS AND CONCLUSION: (1) In vitro experiment: Strontium ranelate-loaded sodium alginate/collagen hydrogel had porous microstructure and sustainable release of strontium ranelate. At 21 days, the cumulative release reached (60.89±0.58)%. Bone marrow mesenchymal stem cell staining showed that both hydrogels had good cytocompatibility. The results of the CCK-8 assay demonstrated that strontium ranelate-loaded sodium alginate/collagen hydrogel could promote the proliferation of bone marrow mesenchymal stem cells. The results of Safranin O staining, Alcian blue staining, immunofluorescence staining and RT-qPCR exhibited that strontium ranelate-loaded sodium alginate/collagen hydrogel could promote chondrogenic differentiation of bone marrow mesenchymal stem cells. Immunofluorescence staining and RT-qPCR revealed that strontium ranelate-loaded sodium alginate/collagen hydrogel could decrease bone resorptivity by increasing the ratio of osteophosphorin/nuclear factor κB receptor activator ligand. (2) In vivo experiment: Micro-CT scan verified that compared with the blank group and control group, the subchondral bone volume fraction and bone mineral density of the knee of rats were increased in the experimental group (P < 0.05, P < 0.01). Histological staining displayed that compared with the blank group and control group, the knee cartilage injury was significantly reduced; the expression of type II collagen was promoted, and the expression of matrix metalloproteinase 2 protein was inhibited in the experimental group (P < 0.05, P < 0.01). (3) These results confirm that the strontium ranelate-loaded sodium alginate/collagen hydrogel can promote the repair of cartilage defects in osteoarthritis and reconstruct the complex interface between cartilage and subchondral bone. [ABSTRACT FROM AUTHOR]

Purpose: To compare the outcomes of treating large cartilage defects in knee osteoarthritis using human allogeneic umbilical cord blood‐derived mesenchymal stem cell (hUCB‐MSC) implantation or arthroscopic microdrilling as a supplementary cartilage regenerative procedure combined with high tibial osteotomy (HTO). Methods: This 1‐year prospective comparative study included 25 patients with large, near full‐thickness cartilage defects (International Cartilage Repair Society grade ≥ IIIB) in the medial femoral condyles and varus malalignment. Defects were treated with hUCB‐MSC implantation or arthroscopic microdrilling combined with HTO. The primary outcomes were pain visual analogue scale and International Knee Documentation Committee subjective scores at 12, 24 and 48 weeks. Secondary outcomes included arthroscopic, histological and magnetic resonance imaging assessments at 1 year. Results: Fifteen and 10 patients were treated via hUCB‐MSC implantation and microdrilling, respectively. Baseline demographics, limb alignment and clinical outcomes did not significantly differ between the groups. Cartilage defects and total restored areas were significantly larger in the hUCB‐MSC group (7.2 ± 1.9 vs. 5.2 ± 2.1 cm2, p = 0.023; 4.5 ± 1.4 vs. 3.0 ± 1.6 cm2, p = 0.035). The proportion of moderate‐to‐strong positive type II collagen staining was significantly higher in the hUCB‐MSC group compared to that in the microdrilled group (93.3% vs. 60%, respectively). Rigidity upon probing resembled that of normal cartilage tissue more in the hUCB‐MSC group (86.7% vs. 50.0%, p = 0.075). Histological findings revealed a higher proportion of hyaline cartilage in the group with implanted hUCB‐MSC (p = 0.041). Conclusion: hUCB‐MSC implantation showed comparable clinical outcomes to those of microdrilling as supplementary cartilage procedures combined with HTO in the short term, despite the significantly larger cartilage defect in the hUCB‐MSC group. The repaired cartilage after hUCB‐MSC implantation showed greater hyaline‐type cartilage with rigidity than that after microdrilling. Level of Evidence: Level II, Prospective Comparative Cohort Study. [ABSTRACT FROM AUTHOR]

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Intact articular cartilage plays a vital role in joint homeostasis. Local cartilage repairs, where defects in the cartilage matrix are filled in and sealed to congruity, are therefore important treatments to restore a joint equilibrium. The base for all cartilage repairs is the cells; either chondrocytes or chondrogeneic cells from bone, synovia and fat tissue. The surgical options include bone marrow stimulation techniques alone or augmented with scaffolds, chondrogeneic cell implantations and osteochondral auto‐ or allografts. The current trend is to choose one‐stage procedures being easier to use from a regulatory point of view. This narrative review provides an overview of the current nonoperative and surgical options available for the repair of various cartilage lesions. Level of Evidence: Level IV. [ABSTRACT FROM AUTHOR]

Copyright of Journal of Materials Engineering / Cailiao Gongcheng is the property of Journal of Materials Engineering Editorial Office and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)