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Background: Microfracture is one surgical treatment strategy for osteochondral lesions of the talus (OLTs) but results in fibrocartilage repair tissue, which has inferior mechanical properties to native hyaline cartilage. Biological regulation of microfracture has been suggested to improve the quality of cartilage repair in patients. Purpose: To determine if administration of losartan, fisetin, or losartan and fisetin combined can enhance microfracture-mediated cartilage repair of OLTs in a rabbit model. Study Design: Controlled laboratory study. Methods: Four-month-old female rabbits were divided into the following groups (8 rabbits per group): microfracture only (microfracture), microfracture plus losartan (losartan), microfracture plus fisetin (fisetin), and microfracture plus losartan and fisetin (losartan+fisetin). A 2.7-mm osteochondral defect and 4 microfracture holes were created in the talar dome cartilage. The rabbits were administered losartan (10 mg/kg/day), fisetin (20 mg/kg/day), or losartan and fisetin orally until euthanized 12 weeks after surgery. Gross evaluation, micro–computed tomography, histology, and immunohistochemistry evaluations of the osteochondral defects were performed as well as quantitative polymerase chain reaction of capsule tissue and enzyme-linked immunosorbent assay of serum. Results: The losartan and fisetin groups had increased International Cartilage Regeneration & Joint Preservation Society macroscopic scores with improved cartilage repair and enhanced subchondral bone healing compared with the microfracture group. However, the losartan+fisetin group did not show a synergistic effect. O'Driscoll histology scores were higher in the losartan and fisetin groups compared with the microfracture group, while the losartan+fisetin group had a lower score than the losartan, fisetin, and microfracture groups. Collagen type 2 staining revealed organized chondrocytes in the losartan and fisetin groups, but the losartan+fisetin group did not show improvement when compared with other groups. Fisetin treatment decreased catalase and transforming growth factor-β1–activated kinase 1 expression in capsular tissue. Conclusion: Concomitant microfracture and biological regulation, using oral administration of either losartan or fisetin, may improve cartilage healing of OLTs; however, losartan and fisetin combined in the current drug administration regimen does not appear to provide synergistic effects. Clinical Relevance: Oral intake of losartan or fisetin may result in beneficial effects on microfracture-mediated cartilage repair of OLTs. [ABSTRACT FROM AUTHOR]

Preclinical models of osteochondral defects (OCDs) are fundamental test beds to evaluate treatment modalities before clinical translation. To increase the rigor and reproducibility of translational science for a robust "go or no‐go," we evaluated disease progression and pain phenotypes within the whole joint for two OCD rat models with same defect size (1.5 x 0.8 mm) placed either in the trochlea or medial condyle of femur. Remarkably, we only found subtle transitory changes to gaits of rats with trochlear defect without any discernible effect to allodynia. At 8‐weeks post‐surgery, anatomical evaluations of joint showed early signs of osteoarthritis with EPIC‐microCT. For the trochlear defect, cartilage attenuation was increased in trochlear, medial, and lateral compartments of the femur. For condylar defect, increased cartilage attenuation was isolated to the medial condyle of the femur. Further, the medial ossicle showed signs of deterioration as indicated with decreased bone mineral density and increased bone surface area to volume ratio. Thus, OCD in a weight‐bearing region of the femur gave rise to more advanced osteoarthritis phenotype within a unilateral joint compartment. Subchondral bone remodeling was evident in both models without any indication of closure of the articular cartilage surface. We conclude that rat OCD, placed in the trochlear or condylar region of the femur, leads to differing severity of osteoarthritis progression. As found herein, repair of the defect with fibrous tissue and subchondral bone is insufficient to alleviate onset of osteoarthritis. Future therapies using rat OCD model should address joint osteoarthritis in addition to repair itself. [ABSTRACT FROM AUTHOR]

Background: Treatment of articular cartilage injury remains a challenging clinical problem in orthopedics. Chitosan-derived biomaterial could be a potential adjuvant treatment to improve cartilage repair. In the current study, we examined the effects of two potential chitosan-derived materials on cartilage regeneration of osteochondral defects in rabbits. Methods: An osteochondral defect was created over the rabbit knee and treated using three approaches: group A received no material (n = 24), group B received chitosan membranes with glucose absorption (CGA; n = 25), and group C received chitosan-glucose derivative membranes obtained via the Maillard reaction (CGMR; n = 25). Cartilage repair over the osteochondral defect was analyzed 12 weeks post-surgery via histological analysis, immunostaining, and reverse transcription-qualitative polymerase chain reaction (RT-qPCR) for type-I and type-II collagen mRNA. Results: According to histological analysis, CGMR-treated defects showed significantly improved modified O'Driscoll scoring when compared with no material- and CGA-treated defects (20.9 ± 4.3 vs. 13.00 ± 2.5 and 17.7 ± 4.6, p < 0.001). Moreover, group C exhibited higher intensity of type-II collagen immunohistochemical staining over the regenerated cartilage than groups A and B, along with increased expression of type-II collagen mRNA by RT-qPCR. Conclusions: CGMR might improve cartilage regeneration in osteochondral defects. [ABSTRACT FROM AUTHOR]

Background: Osteochondral defects of the medial femoral condyle combined with varus malalignment in young and active patients are a debilitating condition, which can result in early osteoarthritis. Osteochondral autologous transfer (OAT) combined with valgus high tibial osteotomy (HTO) might therefore be a comprehensive solution to maintain long-term knee function. Purpose/Hypothesis: The purpose of this study was to report clinical results and survivorship after combined OAT and valgus HTO for symptomatic osteochondral defects of the medial femoral condyle in the setting of varus malalignment at a long-term follow-up. It was hypothesized that undergoing combined OAT and valgus HTO would produce favorable clinical results along with a low rate of conversion to arthroplasty. Study Design: Case series; Level of evidence, 4. Methods: All patients treated between 1998 and 2008 with combined valgus HTO and OAT for deep osteochondral defects of the medial femoral condyle and concomitant varus malalignment >2° without meniscal repair/transplantation, osteoarthritis, or ligamentous instability/reconstruction were included. The survival rates of this combined procedure were evaluated. Failure was defined as conversion to knee joint arthroplasty during the follow-up period. Patient-reported outcomes were collected pre- and postoperatively, including the Lysholm score, visual analog scale score, Knee injury and Osteoarthritis Outcome Score (KOOS), Tegner Activity Scale score, and subjective level of satisfaction (scale 0-10). Results: Of 74 patients who were included for 10-year follow-up, 3 had died. A total of 15 patients were lost to follow-up, so 56 patients could be reevaluated, for a follow-up rate of nearly 80%. The mean age at surgery was 38.8 ± 9.9 years (range, 19.9-62.4 years), and the mean follow-up time was 18.9 ± 3.0 years (median, 18.8 years; range, 14.1-24.8 years). The survival rates were 87% at 10 years, 86% at 15 years, and 77% at 19 years after surgery. At final follow-up, the Lysholm score showed a mean increase of 39 points (95% CI, 25.4-50.0 points; P <.001) from 40 points to 79 points, representing a significant improvement. Overall, 96% of patients surpassed the minimal clinically important difference (MCID) for the Lysholm score. The visual analog scale score decreased by a mean of 4.8 points (range, 5-10 points) from 7.5 points to 2.7 points (P <.001), and 80% of patients surpassed the MCID. The mean Tegner Activity Scale score was 4.5 ± 1.6, and the mean KOOS subscale scores at final follow-up were as follows: Pain: 81 ± 21 (range, 19-100), Symptoms: 80 ± 22 (range, 21-100), Activities of Daily Living: 85 ± 21 (range, 18-100), Sports: 68 ± 32 (range, 0-100), and Quality of Life: 67 ± 28 (range, 0-100). Overall, 78% of the patients were satisfied with the results of the operation. Conclusion: The combination of OAT and valgus HTO presents a viable treatment option for patients affected by osteochondral defects of the medial femoral condyle and concurrent varus malalignment. A sustained and substantial improvement in clinical outcomes, significantly reduced pain severity, and a high rate of long-term survivorship can be anticipated in the long-term follow-up. [ABSTRACT FROM AUTHOR]

Background: There is a lack of procedures that adequately address the subchondral bone structure and function for reconstructing osteochondral defects in the femoral condyles. Purpose: To biomechanically evaluate the tibiofemoral joint contact characteristics before and after reconstruction of femoral condylar osteochondral defects using a novel hybrid reconstructive procedure, which was hypothesized to restore the contact characteristics to the intact condition. Study Design: Controlled laboratory study. Methods: Tibiofemoral contact areas, contact forces, and mean contact pressures were measured in 8 cadaveric knees (mean age 52 ± 11 years; 6 women, 2 men) using a custom testing system and pressure mapping sensors. Five conditions were tested for each condyle: intact, 8-mm defect, 8-mm repair, 10-mm defect, and 10-mm repair. Medial femoral condylar defects were evaluated at 30° of knee flexion and lateral condylar defects were evaluated at 60° of knee flexion, with compressive loads of 50, 100, and 150 N. The defects were reconstructed with a titanium fenestrated threaded implant countersunk in the subchondral bone and an acellular dermal matrix allograft. Repeated-measures analysis of variance with Bonferroni correction for multiple comparisons was used to compare the results between the 5 testing conditions at each load. Results: Medial condylar defects significantly increased mean contact pressure on the lateral side (P <.042), which was restored to the intact levels with repair. The lateral condylar defect decreased the mean contact pressure laterally while increasing the mean pressure medially. The lateral and medial mean contact pressures were restored to intact levels with the 8-mm lateral condylar defect repair. The medial mean contact pressure was restored to intact levels with the 10-mm lateral condylar defect repair. The lateral mean contact pressure decreased compared with the intact state with the lateral condylar 10-mm defect repair. Conclusion: Tibiofemoral joint contact pressure was restored to the intact condition after reconstruction of osteochondral defects with dermal allograft matrix and subchondral implants for the repair of both 8- and 10-mm lateral condylar defects as well as 8-mm medial condylar defects but not completely for 10-mm medial condylar defects. Clinical Relevance: The novel hybrid procedure for osteochondral defect repair restored tibiofemoral joint contact characteristics to normal in a cadaveric model. [ABSTRACT FROM AUTHOR]

Introducrion Repair of the affected articular surface still remains an unsolved problem. The purpose of this study was to assess the efficacy of a biodegradable polycaprolactone implant coated with hydroxyapatite on the healing of an osteochondral defect of the femoral condyle in rats. Materials and methods An osteochondral defect of the medial femoral condyle was modeled in 76 Wistar rats divided into 2 groups. In the experimental group, the defect was replaced with a biodegradable polycaprolactone membrane coated with hydroxyapatite. In the control group, the defect remained untreated. The results were assessed within a year. Results In the experimental group, the animals had a significantly better range of motion at all stages of the experiment than the control animals. The implant ensured the integrity and congruence of the articular surface. On day 180, a newly formed area of the articular surface of the organotypic structure was observed in the defect. Biomechanical properties of the repaied zone restored after 60 days while in the control one they remained lower by 27-29 %. Discussion Filling the defect with an elastic implant made of polyprolactone with hydroxyapatite provided early functional load on the joint. The structure of the implant, simulating the extracellular matrix, promoted the growth, proliferation and directed differentiation of cells in the area of the osteochondral defect. The moderate rate of biodegradability of the material provided gradual replacement of the implant with organ-specific tissues. Conclusion A biodegradable polycaprolactone implant impregnated with hydroxyapatite particles might be effective for experimental osteochondral defect repair.

Natural articular cartilage is a typical self‐healing and superlubrication system capable of maintaining extremely low friction under physiological loadings. Cartilage wear and accidental trauma can cause irreversible defects to cartilage and subchondral bone with a significant decrease in intra‐articular lubrication, leading to the development of severe osteoarthritis and osteochondral defect. To address the important clinical problem of osteochondral defect, a bioinspired hard–soft (PEEK‐lubrication hydrogel) composite scaffold is designed and developed. The polymerization of polyethylene glycol diacrylamide (PEGDAA) and 2‐methacryloyloxyethyl phosphorylcholine (MPC) on polyetheretherketone (PEEK) substrate is achieved by UV initiation to form a strong interfacial bonding, and nano‐hydroxyapatite is deposited on porous PEEK substrate via polydopamine coating to improve osteogenic capability. Accordingly, the composite scaffold is successfully developed with lubrication and osteogenic activity. The tribological tests show that the lubrication performance of the composite scaffold is based on the hydration lubrication mechanism of the upper hydrogel layer, and the in vitro and in vivo experiments demonstrate that the composite scaffold is endowed with excellent biocompatibility and bioactivity. In conclusion, the bioinspired strategy for preparing a hard–soft composite scaffold shows a promising way in the treatment of osteochondral defect and provided a guideline for designing functional PEEK‐based biomaterials in tissue engineering scaffolds. [ABSTRACT FROM AUTHOR]

Background: Microfracture is the most common treatment for cartilage defects of the knee. In microfracture surgery, holes are randomly drilled into the subchondral bone. The effect of the hole's location on its interaction with the cartilage defect site and its influence on the healing process is currently uncertain. Purpose: To investigate the effects of different microfracture locations on healing in a rabbit knee osteochondral defect model. Study Design: Controlled laboratory study. Methods: A total of 29 adult New Zealand White rabbits were divided into 5 groups. In the healthy cartilage control group (n = 5), no surgical procedure was performed. Cylindrical full-thickness cartilage defects (5 × 3 mm) were created in the patellar groove of the remaining 24 rabbits. In the defect control group (n = 6), only the defect was created. A microfracture was performed at the 12-o'clock position (group peripheral single; n = 6), centrally (group central; n = 6), and at the 12- and 6-o'clock positions (group peripheral double; n = 6) of the defect. The animals were sacrificed after 8 weeks. Cartilage healing was evaluated by International Cartilage Regeneration & Joint Preservation Society (ICRS) score, modified O'Driscoll score, immunohistochemical analysis (type 1 collagen, type 2 collagen, and aggrecan), and scanning electron microscopy analysis. Results: In group peripheral double, better cartilage healing was observed in all parameters compared with the other groups (P <.05). Group peripheral double had the greatest amount of filling, with 79% of the defect area filled with fibrocartilage repair tissue. Group peripheral single demonstrated filling of 73% of the defect area, group central 56%, and the defect control group 45%. The ICRS score was significantly higher in group peripheral single compared with group central and the defect control group. Type 2 collagen and aggrecan immunoreactivity were significantly stronger in group central than group peripheral single and the defect control group (P <.05). Conclusion: Microfracture performed at the peripheral margin of the defect had better filling characteristics in a rabbit model. This study suggests that interaction of pluripotent cells released from the microfracture site with the intact cartilage may enhance the quality of the repair tissue. Clinical Relevance: The location of microfracture holes in relation to the peripheral border of the osteochondral defect (to the intact cartilage) is important in both the quality and the quantity of the newly formed repair tissue. [ABSTRACT FROM AUTHOR]

BACKGROUND: Articular cartilage is a kind of hyaline cartilage that has poor self-repair ability. Traditional treatments can merely regenerate fibrocartilage in the defect area but not completely repair a cartilage defect. Hence, it is necessary to explore an effective therapy for cartilage defects through regenerating hyaline cartilage. Platelet-rich plasma is an autologous platelet-rich extract containing various growth factors that has been widely applied in the treatment of articular cartilage defects currently and has shown beneficial therapeutic effects on various types of articular cartilage defects. At present, platelet-rich plasma therapy is a promising treatment for articular cartilage defects. OBJECTIVE: To summarize the preparation, storage and activation of platelet-rich plasma, analyze the properties of platelet-rich plasma in treating different types of articular cartilage defects, and discuss the therapeutic effects of platelet-rich plasma in treating articular cartilage defects. METHODS: Related articles were searched in PubMed, Web of Science, and CNKI using the keywords of “platelet-rich plasma, articular cartilage, prepraration, mechanism, full-thickness cartilage defect, osteochondral defect, weight-bearing areas defect, hip, knee, ankle, osteoarthritis, rheumatoid arthritis in English and Chinese. The search time was from database inception to August 2021. Initially 225 articles were searched and 90 eligible articles were included in final analysis. RESULTS AND CONCLUSION: Platelet-rich plasma contains high concentrations of growth factors that can play roles in promoting chondrocyte proliferation, regulating cartilage matrix secretion, inducing stem cell proliferation and differentiation, forming a strong scaffold structure, reducing inflammation, lubricating rough articular surface and reducing immune response in vivo, which can meet the requirements for treating various types of cartilage defects. Platelet rich plasma has a good therapeutic effect on full-thickness cartilage defects, osteochondral defects, weight-bearing area cartilage defects, osteoarthritis, and rheumatoid arthritis. Platelet-rich plasma also has the potential to treat growth plate defects considering its curative effects on these abnormal conditions. [ABSTRACT FROM AUTHOR]

Background: Osteochondral defects of the talus can be effectively treated using microfracture, which is technically safe, accessible, and affordable. However, fibrous tissue and fibrocartilage comprise the majority of tissue repairs resulting from these procedures. These tissue types lack the mechanical characteristics of native hyaline cartilage and might significantly contribute to the decline in long-term outcomes. Recombinant human-bone morphogenetic protein–2 (rhBMP-2) has been shown to promote matrix synthesis and increase cartilage formation, thus enhancing chondrogenesis in vitro. Purpose: This study aimed to evaluate the treatment ability of combining rhBMP-2 with microfracture in rabbit talus osteochondral defect. Study Design: Controlled laboratory study. Methods: A full-thickness chondral defect (3 × 3 × 2 mm) was constructed in the center talar dome of 24 New Zealand White male rabbits, which were then divided into 4 groups of 6. Each group received the appropriate treatment: group 1 (control; no treatment of defect), group 2 (microfracture treatment), group 3 (rhBMP-2/hydroxyapatite treatment), and group 4 (microfracture combined with rhBMP-2/hydroxyapatite treatment). Animals were sacrificed at 2, 4, and 6 weeks postoperatively. The International Cartilage Regeneration & Joint Preservation Society macroscopic score, which considers the degree of defect repair, the integration to the border zone, and the macroscopic appearance, was used to assess the repaired tissue's macroscopic appearance. Subchondral bone regeneration in defects was analyzed using micro–computed tomography, and the histological findings were graded using a modified version of the Wakitani scoring system for osteochondral repair. Results: At 2, 4, and 6 weeks, micro-computed tomography analysis revealed that groups 3 and 4 exhibited subchondral bone healing that was more significantly improved compared with groups 1. No sample showed excessive bone growth from the subchondral bone area. According to macroscopic and histological results, group 4 showed higher-quality cartilage and more accelerated cartilage regeneration than the other groups over time. Conclusion: These findings show that osteochondral defect repair in a rabbit talus model could be effectively accelerated and improved by combining rhBMP-2 with microfracture. Clinical Relevance: Using rhBMP-2 in combination with microfracture may enhance the repair of talar osteochondral lesions. [ABSTRACT FROM AUTHOR]

• Chondrogenic/osteogenic ECM membranes could promote chondrogenic/osteogenic abilities of bilayer scaffolds. • Repair of osteochondral defect is significantly improved with the ECM membranes wrapped bilayer scaffold. • Bilayer scaffold is prepared from Graphene oxide-collagen with (bottom layer)/and without Nano-hydroxyapatite (top layers). Both bone and cartilage microenvironments play a crucial role in the regeneration of osteochondral defects caused by osteoarthritis (OA). A major challenge is how to simulate gradient changing mechanical properties and inducing abilities of regenerative microenvironments on the integrated scaffold to achieve simultaneous regeneration. In this work, a concept of biphasic ECM assembled graphene oxide-collagen (GO-COL)/ Nano-hydroxyapatite (nHap) composite is proposed. GO-COL/nHap bilayer scaffold with gradient concentration was formed by crosslinking and freeze-drying in stages to mimic the gradient distribution of mechanical properties of articular cartilage and bone. Then we prepared chondrogenic/osteogenic ECM membranes (CgECM/OgECM) with chondrocytes from rat knee respectively, and assembled them onto corresponding layers. The morphology, physical properties, biocompatibility, and osteochondrogenic capability of the scaffold were evaluated in vitro and in vivo. Mechanically, gene expression and protein level assessments showed greater osteochondrogenic activity in the biphasic ECM scaffold group compared to the GO-COL bilayer scaffold group. In vivo studies using a rat knee osteochondral defect model further confirmed the superior repair effect of the biphasic ECM-scaffold group compared to the blank group. Taken together, the proposed ECM assembled GO-COL/nHap strategy open a window to realize different microenvironment mimicking in a whole scaffold, making it a potential off-the-shelf method for osteochondral tissue engineering. [ABSTRACT FROM AUTHOR]

Because of limited self-healing ability, the treatment of articular cartilage defects is still an important clinical challenge. Hydrogel-based biomaterials have broad application prospects in articular cartilage repair. In this study, gelatin methacrylate (GelMA)and silk fibroin (SF) were combined to form a composite hydrogel with an interpenetrating network (IPN) structure under ultraviolet irradiation and ethanol treatment. Introducing silk fibroin into GelMA hydrogel significantly increased mechanical strength as compressive modulus reached 300 kPa in a GelMA/SF-5 (50 mg/mL silk fibroin) group. Moreover, composite IPN hydrogels demonstrated reduced swelling ratios and favorable biocompatibility and supported chondrogenesis of bone mesenchymal stem cells (BMSCs) at day 7 and day 14. Additionally, significantly higher gene expressions of Col-2, Acan, and Sox-9 (p < 0.01) were found in IPN hydrogel groups when compared with the GelMA group. An in vivo study was performed to confirm that the GelMA-SF IPN hydrogel could promote cartilage regeneration. The results showed partial regeneration of cartilage in groups treated with hydrogels only and satisfactory cartilage repair in groups of cell-seeded hydrogels, indicating the necessity of additional seeding cells in hydro-gel-based cartilage treatment. Therefore, our results suggest that the GelMA/SF IPN hydrogels may be a potential functional material in cartilage repair and regeneration. [ABSTRACT FROM AUTHOR]

Background: The first-line clinical strategy for small cartilage/osteochondral defects is microfracture (MF). However, its repair efficacy needs improvement. Hypothesis: Appropriate energy radial shockwave stimulation in MF holes would greatly improve repair efficacy in the porcine osteochondral defect model, and it may obtain comparable performance with common tissue engineering techniques. Study Design: Controlled laboratory study. Methods: Osteochondral defect models (8-mm diameter, 3-mm depth) were established in the weightbearing area of Bama pigs' medial femoral condyles. In total, 25 minipigs were randomly divided into 5 groups: control (Con; without treatment), MF, MF augmentation (MF+; treated with appropriate energy radial shockwave stimulation in MF holes after MF), tissue engineering (TE; treated with compounds of microcarrier and bone marrow mesenchymal stem cells), and sham (as the positive control). After 3 months of intervention, osteochondral specimens were harvested for macroscopic, radiological, biomechanical, and histological evaluations. The statistical data were analyzed using 1-way analysis of variance. Results: Based on the macroscopic appearance, the smoothness and integration of the repaired tissue in the MF+ group were improved when compared with the Con and MF groups. The histological staining suggested more abundant cartilaginous matrix deposition in the MF+ group versus the Con and MF groups. The general scores of the macroscopic and histological appearances were comparable in the MF+ and the TE groups. The high signal areas of the osteochondral unit in the magnetic resonance images were significantly decreased in the MF+ group, with no difference with the TE group. The micro–computed tomography data demonstrated the safety of direct in situ radial shockwave performance. Biomechanical tests revealed that the repaired tissue's Young modulus was highest in the MF+ group and not statistically different from that in the TE group. Conclusion: Direct in situ radial shockwave stimulation with appropriate energy significantly improves the short-term repair efficacy of MF. More encouragingly, the MF+ group in our study obtained repair performance comparable with the TE therapy. Clinical Relevance: This strategy is easy to perform and can readily be generalized with safety and higher cartilage repair efficacy. Moreover, it is expected to be accomplished under arthroscopy, indicating tremendous clinical transformative value. [ABSTRACT FROM AUTHOR]

Background: Chondral defects in the knee have biomechanical differences because of defect size and location. Prior literature only compares the maximum stress experienced with large defects. Hypothesis: It was hypothesized that pressure surrounding the chondral defect would increase with size and vary in location, such that a size cutoff exists that suggests surgical intervention. Study Design: Controlled laboratory study. Methods: Isolated chondral defects from 0.09 to 1.0 cm2 were created on the medial and lateral femoral condyles of 6 human cadaveric knees. The knees were fixed to a uniaxial load frame and loaded from 0 to 600 N at full extension. Another defect was created at the point of tibiofemoral contact at 30° of flexion. Tibiofemoral contact pressures were measured. Peak contact pressure was the highest value in the area delimited within a 3-mm rim around the defect. The location of the peak contact pressure was determined. Results: At full extension, the mean maximum pressures on the medial femoral condyle ranged from 4.30 to 6.91 MPa at 0.09 and 1.0 cm2, respectively (P <.01). The location of the peak pressure was found posteromedial in defects between 0.09 and 0.25 cm2, shifting anterolaterally at sizes 0.49 and 1.0 cm2 (P <.01). The maximum pressures on the lateral femoral condyle ranged from 3.63 to 5.81 MPa at 0.09 and 1.0 cm2, respectively (P =.02). The location of the peak contact pressure point was anterolateral in defects between 0.09 and 0.25 cm2, shifting posterolaterally at 0.49 and 1.0 cm2 (P <.01). No differences in contact pressure between full extension and 30° of flexion were found for either the lateral or medial condyles. Conclusion: Full-thickness chondral defects bilaterally had a significant increase in contact pressure between defect sizes of 0.49 and 1.0 cm2. The location of the maximum contact pressures surrounding the lesion also varied with larger defects. Contact area redistribution and cartilage stress change may affect adjacent cartilage integrity. Clinical Relevance: Size cutoffs may exist earlier in the natural history of chondral defects than previously realized, suggesting a lower threshold for intervention. [ABSTRACT FROM AUTHOR]

Background: It is unclear whether the results of osteochondral transplant using autografts or allografts for talar osteochondral defect are equivalent. Purpose: A systematic review of the literature was conducted to compare allografts and autografts in terms of patient-reported outcome measures (PROMs), MRI findings, and complications. Study Design: Systematic review; Level of evidence, 4. Methods: This study was conducted according to the PRISMA guidelines. The literature search was conducted in February 2021. All studies investigating the outcomes of allograft and/or autograft osteochondral transplant as management for osteochondral defects of the talus were accessed. The outcomes of interest were visual analog scale (VAS) score for pain, American Orthopaedic Foot and Ankle Society (AOFAS) score, and Magnetic Resonance Observation of Cartilage Repair Tissue (MOCART) score. Data concerning the rates of failure and revision surgery were also collected. Continuous data were analyzed using the mean difference (MD), whereas binary data were evaluated with the odds ratio (OR) effect measure. Results: Data from 40 studies (1174 procedures) with a mean follow-up of 46.5 ± 25 months were retrieved. There was comparability concerning the length of follow-up, male to female ratio, mean age, body mass index, defect size, VAS score, and AOFAS score (P >.1) between the groups at baseline. At the last follow-up, the MOCART (MD, 10.5; P =.04) and AOFAS (MD, 4.8; P =.04) scores were better in the autograft group. The VAS score was similar between the 2 groups (P =.4). At the last follow-up, autografts demonstrated lower rate of revision surgery (OR, 7.2; P <.0001) and failure (OR, 5.1; P <.0001). Conclusion: Based on the main findings of the present systematic review, talar osteochondral transplant using allografts was associated with higher rates of failure and revision compared with autografts at midterm follow-up. [ABSTRACT FROM AUTHOR]

The treatment of osteochondral joint lesions requires the regeneration of both articular cartilage and subchondral bone tissue. Scaffold-based strategies aimed at mimicking the native osteochondral structure have been explored with mixed results. The aim of this study was to evaluate the regenerative potential of a tri-layered osteochondral cell-free scaffold in a large animal model at both 6 and 12 months of follow-up. Bilateral critical-sized osteochondral defects were created in 22 sheep. One defect was filled with the scaffold, whereas the contralateral was left empty. The repair tissue quality was evaluated at 6 and 12 months of follow-up in terms of macroscopic appearance, histology, trabecular bone formation, and inflammation grade. The mean global ICRS II score in the scaffold and control groups was 41 ± 11 vs 30 ± 6 at 6 months (p = 0.004) and 54 ± 13 vs 37 ± 11 at 12 months (p = 0.002), respectively. A higher percentage of bone was found in the treatment group compared to controls both at 6 (BV/TV 48.8 ± 8.6 % vs 37.4 ± 9.5 %, respectively; p < 0.001) and 12 months (BV/TV 51.8 ± 8.8 % vs 42.1 ± 12.6 %, respectively; p = 0.023). No significant levels of inflammation were seen. These results demonstrated the scaffold safety and potential to regenerate both cartilage and subchondral tissues in a large animal model of knee osteochondral lesions. [Display omitted] [ABSTRACT FROM AUTHOR]

• Systematic summary of the physiological gradients at the osteochondral interface. • Fabrication method of cell, composition, pore size, mechanical gradient scaffolds. • Evaluation of repairing effect of gradient scaffolds on damaged osteochondral tissue. In recent years, the incidence of osteoarthritis (OA) has been increasing worldwide. This disease not only affects the articular cartilage but also impairs the subchondral bone and surrounding tissues. Therefore, there has been much research dedicated to osteochondral defect repair. In tissue engineering, integrated gradient tissue-engineered osteochondral scaffold has been proposed as a promising treatment, that can simultaneously repair articular cartilage, osteochondral interface, and subchondral bone. It is possible to identify a variety of physiological gradients between the surface of the articular cartilage and the subchondral bone. Simulating these gradients in scaffold design is an effective way to regenerate osteochondral tissue. Starting from various physiological gradients, this review provides an overview of current research on gradient scaffolds for the repair of osteochondral tissue. [ABSTRACT FROM AUTHOR]

Background: Seeding cells are key factors in cell-based cartilage tissue regeneration. Monoculture of either chondrocyte or mesenchymal stem cells has several limitations. In recent years, co-culture strategies have provided potential solutions. In this study, directly co-cultured rat costal chondrocytes (CCs) and human Wharton's jelly mesenchymal stem (hWJMSCs) cells were evaluated as a candidate to regenerate articular cartilage. Methods: Rat CCs are directly co-cultured with hWJMSCs in a pellet model at different ratios (3:1, 1:1, 1:3) for 21 days. The monoculture pellets were used as controls. RT-qPCR, biochemical assays, histological staining and evaluations were performed to analyze the chondrogenic differentiation of each group. The 1:1 ratio co-culture pellet group together with monoculture controls were implanted into the osteochondral defects made on the femoral grooves of the rats for 4, 8, 12 weeks. Then, macroscopic and histological evaluations were performed. Results: Compared to rat CCs pellet group, 3:1 and 1:1 ratio group demonstrated similar extracellular matrix production but less hypertrophy intendency. Immunochemistry staining found the consistent results. RT-PCR analysis indicated that chondrogenesis was promoted in co-cultured rat CCs, while expressions of hypertrophic genes were inhibited. However, hWJMSCs showed only slightly improved in chondrogenesis but not significantly different in hypertrophic expressions. In vivo experiments showed that all the pellets filled the defects but co-culture pellets demonstrated reduced hypertrophy, better surrounding cartilage integration and appropriate subchondral bone remodeling. Conclusion: Co-culture of rat CCs and hWJMSCs demonstrated stable chondrogenic phenotype and decreased hypertrophic intendency in both vitro and vivo. These results suggest this co-culture combination as a promising candidate in articular cartilage regeneration. [ABSTRACT FROM AUTHOR]

Background: Many procedures to reconstruct osteochondral defects of the elbow radiocapitellar (RC) joint lack versatility or durability or do not directly address the subchondral bone structure and function. Purpose/Hypothesis: To biomechanically characterize the RC joint contact area, force, pressure, and peak pressure before and after reconstruction of osteochondral defects using a novel hybrid reconstructive procedure. It was hypothesized that the procedure would restore the contact characteristics to the intact condition. Study Design: Controlled laboratory study. Methods: A total of 10 cadaveric elbows (mean age 67 ± 2.7 years) were dissected to isolate the humerus and radial head. RC contact area, contact force, mean contact pressure, and peak contact pressure were measured with the elbow at 45° of flexion and neutral forearm rotation at compressive loads of 25, 50, and 75 N. Osteochondral defects 8 and 11 mm in diameter were created at the center of the capitellum; the defects were then reconstructed with a titanium fenestrated threaded implant, countersunk in the subchondral bone, with an acellular dermal matrix allograft sutured in place on top of the implant. Five conditions (intact, 8-mm defect, 8-mm repair, 11-mm defect, and 11-mm repair) were tested and results were compared using repeated-measures analysis of variance. Results: Both 8- and 11-mm defects significantly increased RC mean contact pressure at all compressive loads (P ≤.008) and significantly increased peak contact pressure at compressive loads of 50 and 75 N (P <.002) compared with the intact condition. Repair of the 8-mm defect significantly decreased RC mean contact pressure at 25- and 50-N loads (P ≤.009) and significantly decreased peak contact pressure at 50- and 75-N loads (P ≤.035) compared with the defect condition. Repair of the 11-mm defect decreased mean contact pressure significantly at all compressive loads (P ≤.001) and peak contact pressure at 50- and 75-N loads (P <.044) compared with the defect condition. Conclusion: RC joint contact pressure was restored to intact conditions while avoiding increased peak contact pressure or edge loading after repairing osteochondral defects related to osteochondrosis with a novel hybrid reconstruction technique. Clinical Relevance: This hybrid procedure that addresses the entire osteochondral unit may provide a new treatment option for osteochondral defects. [ABSTRACT FROM AUTHOR]

The symptomatic full-thickness cartilage lesions or cartilage degeneration leads to the destruction of the normal chondral architecture and bone structure in affected area, causes the osteoarthritis, and general damage to the health. Knee joints are most frequently affected by this condition. The permanent damage of the articular cartilage and subchondral bone has motivated many scientists and clinicians to explore new methods of regeneration of osteochondral defects, such as novel materials. We studied the potential of the biocement based on calcium phosphate consisting of a mixture of four amino acids (glycine, proline, hydroxyproline and lysine) in the regenerating process of the artificially created osteochondral defect on the porcine medial femoral condyle in the stifle joint. The mass ratio of the amino acids in biocement CAL was 4:2:2:1. The Ca/P ratio in cement was 1.67 which correspond with ratio in hydroxyapatite. We compared the results with spontaneous healing of an artificially created cyst with that of the healthy tissue. The animal group treated with biocement paste CAL presented completely filled osteochondral defects. The results were confirmed by histological and radiological assessments, which have shown regenerated chondral and bone tissue in the examined knee joints. Macroscopic evaluation showed that neocartilage was well integrated with the adjacent native cartilage in animal group with biocement CAL, compared with healing of the artificial cyst, where treated cartilage surfaces were visibly lower than the surrounding native cartilage surface and a border between native and restored tissue was apparent. The qualitative assessment of the implant histology specimens showed full regeneration of the hyaline cartilage and subchondral bone in animals with biocement CAL. The artificial cyst group showed remarkable fibrillation. The detailed MRI analysis of cross-section of osteochondral defect confirmed the complete cartilage and subchondral bone healing where the thickness of the regenerated cartilage was 1.5 mm. The MRI imaging of defects in the artificial cyst group showed incomplete healing, neo cartilage tissue reduced up to 50%.

Because of limited self-healing ability, the treatment of articular cartilage defects is still an important clinical challenge. Hydrogel-based biomaterials have broad application prospects in articular cartilage repair. In this study, gelatin methacrylate (GelMA)and silk fibroin (SF) were combined to form a composite hydrogel with an interpenetrating network (IPN) structure under ultraviolet irradiation and ethanol treatment. Introducing silk fibroin into GelMA hydrogel significantly increased mechanical strength as compressive modulus reached 300 kPa in a GelMA/SF-5 (50 mg/mL silk fibroin) group. Moreover, composite IPN hydrogels demonstrated reduced swelling ratios and favorable biocompatibility and supported chondrogenesis of bone mesenchymal stem cells (BMSCs) at day 7 and day 14. Additionally, significantly higher gene expressions of Col-2, Acan, and Sox-9 (p < 0.01) were found in IPN hydrogel groups when compared with the GelMA group. An in vivo study was performed to confirm that the GelMA-SF IPN hydrogel could promote cartilage regeneration. The results showed partial regeneration of cartilage in groups treated with hydrogels only and satisfactory cartilage repair in groups of cell-seeded hydrogels, indicating the necessity of additional seeding cells in hydro-gel-based cartilage treatment. Therefore, our results suggest that the GelMA/SF IPN hydrogels may be a potential functional material in cartilage repair and regeneration.

Background: Hemiarthroplasty using a polyvinyl alcohol (PVA) hydrogel synthetic implant has been suggested as a good alternative to arthrodesis for the treatment of hallux rigidus. However, failure rates as high as 20% have been recorded. Purpose: To characterize the pathological processes in bone, cartilage, and the synovial membrane after PVA hemiarthroplasty in an ovine model with 6 months of follow-up. Study Design: Controlled laboratory study. Methods: A unilateral osteochondral defect (8-mm diameter × 10-mm depth) was made in the medial femoral condyle in 6 sheep. Animals were randomized to receive a PVA implant (n = 4) or to have an empty defect (n = 2) and were monitored for 6 months. Patellofemoral radiographs were obtained at monthly intervals, and quantitative computed tomography was performed at the end of the study. After death, the joints were macroscopically evaluated and scored. Osteochondral and synovial membrane histological findings were assessed using modified Osteoarthritis Research Society International (OARSI) and aseptic lymphocyte-dominated vasculitis-associated lesion (ALVAL) scoring systems. Immunohistochemistry using Iba1 was performed to evaluate activated macrophage infiltration. Results: Overall, 2 sheep with PVA implants were euthanized at 1 and 5 months because of uncontrollable pain and lameness (failed implants). Quantitative computed tomography showed that sheep with failed implants had 2.1-fold more osteolysis than those with successful implants. The sheep with failed implants had osteoarthritis with extensive glycosaminoglycan loss and cartilage fibrillation of the condyle and opposing tibial surface on histological examination. A foreign body reaction with severe chronic lymphoplasmacytic and granulomatous inflammation with giant cells was detected surrounding the implant. The synovial membrane ALVAL score was 9 of 19 and 14 of 19 in failed implants with synovial hyperplasia and lymphoplasmacytic and macrophage infiltration. In contrast, the synovial membrane in successful implants and empty defects was normal (ALVAL score = 0/19). Immunolabeling for Iba1 in failed implants confirmed extensive and dense macrophage infiltration within the condyle and synovial membrane, with the highest immunoreactive score (9/9). Conclusion: PVA hydrogel implants had a 50% failure rate with uncontrollable pain, severe osteolysis, inflammation, and foreign body reactions. Clinical Relevance: The failure rate and pathological characteristics of the PVA implants suggest that their use should not be continued in human patients without further in vivo safety studies. [ABSTRACT FROM AUTHOR]

Background: The physiologic regenerative capacity of cartilage is severely limited. Current studies on the repair of osteochondral defects (OCDs) have mainly focused on the regeneration of cartilage tissues. The antler cartilage is a unique regenerative cartilage that has the potential for cartilage repair. Methods: Antler decellularized cartilage-derived matrix scaffolds (adCDMs) were prepared by combining freezing-thawing and enzymatic degradation. Their DNA, glycosaminoglycans (GAGs), and collagen content were then detected. Biosafety and biocompatibility were evaluated by pyrogen detection, hemolysis analysis, cytotoxicity evaluation, and subcutaneous implantation experiments. adCDMs were implanted into rabbit articular cartilage defects for 2 months to evaluate their therapeutic effects. Results: AdCDMs were observed to be rich in collagen and GAGs and devoid of cells. AdCDMs were also determined to have good biosafety and biocompatibility. Both four- and eight-week treatments of OCDs showed a flat and smooth surface of the healing cartilage at the adCDMs filled site. The international cartilage repair society scores (ICRS) of adCDMs were significantly higher than those of controls (porcine dCDMs and normal saline) (p < 0.05). The repaired tissue in the adCDM group was fibrotic with high collagen, specifically, type II collagen. Conclusions: We concluded that adCDMs could achieve excellent cartilage regeneration repair in a rabbit knee OCDs model. Our study stresses the importance and benefits of adCDMs in bone formation and overall anatomical reconstitution, and it provides a novel source for developing cartilage-regenerating repair materials. [ABSTRACT FROM AUTHOR]

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Background: Ultrapurified alginate (UPAL) gel implantation has been demonstrated as effective in cartilage repair for osteochondral defects; however, cell transplantation within UPAL gels would be required to treat larger defects. Hypothesis: The combination of UPAL gel and bone marrow aspirate concentrate (BMAC) would enhance cartilage repair and subchondral bone repair for large osteochondral defects. Study Design: Controlled laboratory study. Methods: A total of 104 osteochondral defects (1 defect per knee) of 52 rabbits were randomly divided into 4 groups (26 defects per group): defects without any treatment (Defect group), defects treated using UPAL gel alone (UPAL group), defects treated using UPAL gel containing allogenic bone marrow mesenchymal stromal cells (UPAL-MSC group), and defects treated using UPAL gel containing BMAC (UPAL-BMAC group). At 4 and 16 weeks postoperatively, macroscopic and histologic evaluations and measurements of repaired subchondral bone volumes of reparative tissues were performed. Collagen orientation and mechanical properties of the reparative tissue were assessed at 16 weeks. Results: The defects in the UPAL-BMAC group were repaired with hyaline-like cartilage with well-organized collagen structures. The histologic scores at 4 weeks were significantly higher in the UPAL-BMAC group (16.9 ± 2.0) than in the Defect group (4.7 ± 1.9; P <.05), the UPAL group (10.0 ± 3.3; P <.05), and the UPAL-MSC group (12.2 ± 2.9; P <.05). At 16 weeks, the score in the UPAL-BMAC group (24.4 ± 1.7) was significantly higher than those in the Defect group (9.0 ± 3.7; P <.05), the UPAL group (14.2 ± 3.9; P <.05), and the UPAL-MSC group (16.3 ± 3.6; P <.05). At 4 and 16 weeks, the macroscopic evaluations were significantly superior in the UPAL-BMAC group compared with the other groups, and the values of repaired subchondral bone volumes in the UPAL-BMAC group were significantly higher than those in the Defect and UPAL groups. The mechanical properties of the reparative tissues were significantly better in the UPAL-BMAC group than in the other groups. Conclusion: The implantation of UPAL gel containing BMAC-enhanced hyaline-like cartilage repair and subchondral bone repair of osteochondral defects in a rabbit knee model. Clinical Relevance: These data support the potential clinical application of 1-step treatment for large osteochondral defects using biomaterial implantation with cell transplantation. [ABSTRACT FROM AUTHOR]

Background: Long-term outcomes of current clinical interventions for osteochondral defect are less than satisfactory. One possible reason is an ignorance of the interface structure between cartilage and subchondral bone, the calcified cartilage zone (CCZ). However, the importance of natural CCZ in osteochondral defects has not been directly described. Purpose: To explore the feasibility of fabricating trilayer scaffold containing natural CCZ for osteochondral defects and the role of CCZ in the repair process. Study Design: Controlled laboratory study. Methods: The scaffold was prepared by cross-linking lyophilized type II collagen sponge and acellular normal pig subchondral bone with or without natural CCZ. Autologous bone marrow stem cells (BMSCs) of minipig were mixed with type II collagen gel and injected into the cartilage layer of the scaffold before operation. Thirty minipigs were randomly divided into CCZ (n = 10), non-CCZ (n = 10), and blank control (n = 10) groups. An 8 mm–diameter full-thickness osteochondral defect was created on the trochlear surface, and scaffold containing BMSCs was transplanted into the defect according to grouping requirements. At 12 and 24 weeks postoperatively, specimens were assessed by macroscopic observation, magnetic resonance imaging examination, and histological observations (hematoxylin and eosin, Safranin O–fast green, type II collagen immunohistochemical, and Sirius red staining). Semiquantitative cartilage repair scoring was conducted using the MOCART (Magnetic Resonance Observation of Cartilage Repair Tissue) system and the O'Driscoll repaired cartilage value system. Results: The defects in the blank control and non-CCZ groups were filled with fibrous tissue, while the cartilage layer of the CCZ group was mainly repaired by hyaline cartilage at 24 weeks postoperatively. The superior repair outcome of the CCZ group was confirmed by MOCART and O'Driscoll score. Conclusion: The trilayer scaffold containing natural CCZ obtained the best repair effect compared with the non-CCZ scaffold and the blank control, indicating the importance of the CCZ in osteochondral tissue engineering. Clinical Relevance: This study demonstrates the necessity to reconstruct CCZ in clinical osteochondral defect repair and provides a possible strategy for osteochondral tissue engineering. [ABSTRACT FROM AUTHOR]

Purpose: Intra-articular malunion of tibial plateau fracture is a complex problem to treat. We are presenting outcomes of our series of patients of malunited tibial plateau fractures treated with osteo-chondro-meniscal allograft from lateral tibial plateau harvested from patients undergoing total knee arthroplasty (TKA). Methods: The technique was used in four patients. Preoperative computed tomography (CT) scan was used to match donor and recipient graft dimensions and to measure any malalignment. Patients were evaluated for Visual analogue Scale (VAS) for pain (scale 1–10 cm), WOMAC (Western Ontario McMaster Osteo-Arthritis Index) score, knee range of motion, and limb alignment. Results: There were three medial tibial plateau malunions and one lateral tibial plateau malunion. Articular comminution with depression was seen in all of them. One patient underwent concurrent high tibial osteotomy for the elevation of the medial tibial plateau and posterior cruciate ligament reconstruction was performed concurrently in one patient. All patients showed improvement in knee range of motion, WOMAC score, and VAS score for knee pain. Limb alignment improved in all cases. Radiologically there was consolidation of the allograft in all the cases at 6 months. The mean follow-up was 15.2 months (range 12–18 months). Conclusion: Osteochondral allograft can be a good choice for reconstructing large articular cartilage defects in tibial plateau malunions. Osteo-chondro-meniscal grafts obtained during TKA can be a viable alternative for reconstructing such defects with excellent early clinical, functional, and radiological outcomes. Level of Evidence: IV. [ABSTRACT FROM AUTHOR]

Osteochondral defects of the ankle (OCD) are being increasingly identified as a clinically significant consequence of injury to the ankle, with the potential to lead to osteoarthritis if left untreated. The aim of this retrospective cohort study was to evaluate a single-stage treatment of OCD, based on bone marrow aspirate (BMA) centrifuged to produce bone marrow concentrate (BMC). In a dual syringe, the concentrate was mixed with thrombin in one syringe, whereas hyaluronan and fibrinogen were mixed in a second syringe. The two mixtures were then injected and combined into the prepared defect. Clinical outcome and quality of life scores (MOXFQ and EQ-5D) were collected at baseline and yearly thereafter. Multilevel models were used to analyse the pattern of scores over time. Ninety-four patients were treated between 2015 and 2020. The means of each of the three components of the MOXFQ significantly improved between baseline and 1 year (p < 0.001 for each component), with no further change from year 1 to year 3. The EQ-5D index also improved significantly from baseline to 1 year, with no evidence for further change. Our results strongly indicate that this BMC treatment is safe for, and well tolerated by, patients with OCD of the ankle as both primary treatment and those who have failed primary treatment. This technique provides a safe, efficacious alternative to currently employed cartilage repair techniques, with favourable outcomes and a low complication rate at 36 months.

Bioactive scaffolds from synthetical polymers or decellularized cartilage matrices have been widely used in osteochondral regeneration. However, the risks of potential immunological reactions and the inevitable donor morbidity of these scaffolds have limited their practical applications. To address these issues, a biological extracellular matrix (ECM) scaffold derived from allogenic decellularized bone marrow mesenchymal stem cell (BMSC) sheets was established for osteochondral reconstruction. BMSCs were induced to form cell sheets. Three different concentrations of sodium dodecyl sulfate (SDS), namely, 0.5%, 1%, and 3%, were used to decellularize these BMSC sheets to prepare the ECM. Histological and microstructural observations were performed in vitro and then the ECM scaffolds were implanted into osteochondral defects in rabbits to evaluate the repair effect in vivo. Treatment with 0.5% SDS not only efficiently removed BMSCs but also successfully preserved the original structure and bioactive components of the ECM When compared with the 1% and 3% SDS groups, histological observations substantiated the superior repair effect of osteochondral defects, including the simultaneous regeneration of well-vascularized subchondral bone and avascular articular cartilage integrated with native tissues in the 0.5% SDS group. Moreover, RT-PCR indicated that ECM scaffolds could promote the osteogenic differentiation potential of BMSCs under osteogenic conditions while increasing the chondrogenic differentiation potential of BMSCs under chondrogenic conditions. Allogenic BMSC sheets decellularized with 0.5% SDS treatment increased the recruitment of BMSCs and significantly improved the regeneration of osteochondral defects in rabbits, thus providing a prospective approach for both articular cartilage and subchondral bone reconstruction with cell-free transplantation. Image, graphical abstract [ABSTRACT FROM AUTHOR]

Objective: We used biomimetic scaffolds, chondral scaffolds, and microfractures to repair experimentally created osteochondral defects in rat knees and then compared the results of each method. Materials and Methods: We used a total of 56 female Wistar albino rats. The rats were grouped into 4 groups, with 14 rats each: biomimetic scaffold, chondral scaffold, microfracture, and control groups. Cylindrical full-thickness osteochondral defects 2.5 mm in diameter and 2 mm in depth were drilled into the right knees with the rats under general anesthesia. The knees of all rats were operated again after 4 weeks. Biomimetic and chondral scaffolds were classified into two groups. Microfractures 0.5 mm in diameter and 0.8 mm in depth were created in the rats of the microfracture group. The control group received no treatment. All the rats were observed for 6 weeks and then sacrificed, with samples subjected to macroscopic and histopathological examinations. Results: The macroscopic and histopathological results in the biomimetic scaffold group differed significantly from those of the other treatment groups (p<0.05). When we compared the 3 treatment groups, the results of the chondral scaffold group were better than those of the microfracture group. The results of the microfracture group were somewhat better than those of the control group, but the result was not statistically significant (p>0.05). Conclusions: Nanocomposite multilayer biomimetic scaffolds were better than chondral scaffolds and microfractures when used to treat osteochondral defects. [ABSTRACT FROM AUTHOR]

BACKGROUND: Although desired cartilage repair has been realized via tissue engineering technology, these achievements mainly focus on small-size defect under a normal physical condition. However, cartilage defects are always accompanied by the underlying diseases in clinical practice, such as osteoarthritis and rheumatoid arthritis. Meanwhile, the location, scope, and depth of cartilage defects are uncertain, which brings a great challenge in cartilage tissue repair. OBJECTlVE: To summarize the methods of repairing articular cartilage defects at different locations and under inflammatory condition. METHODS: We searched PubMed and CNKI with the search terms "cartilage defect regeneration, osteochondral, growth plate, weight-bearing area, inflammatory" in Chiense and English to retrieve related papers published before March 2019. A total of 209 papers were retrieved and 86 were included in the final analysis according to inclusion and exclusion criteria. RESULTS AND CONCLUSION: For articular cartilage defects under different special conditions, the repair goals and strategies are different. For repair of full-layer cartilage defects and osteochondral structure defects, multi-layered scaffolds are often used to repair the unique stratified cartilage structure and subchondral bone structure, while avoiding the problem of heterotopic ossification in neonatal cartilage. To avoid deformity after long bone maturation, growth factors such as insulin-like growth factor and bone morphogenetic protein 7 should be added to continuously stimulate the repair of the growth plate and promote bone growth. For cartilage repair in the weight-bearing area, the scaffolds should have good mechanical property, which ensure not to undergo severe deformation and structural damage when loaded. In addition, the new cartilage tissue has sufficient mechanical strength to support sustained longitudinal pressure and wear. For cartilage defects in the inflammatory state, both inflammation management and cartilage defect repair should be considered, and introduction of mesenchymal stem cells can regulate immune function and promote tissue regeneration, such that articular cartilage defect can be completely repaired. [ABSTRACT FROM AUTHOR]

Background: Human amniotic mesenchymal stem cells (hAMSCs) are being widely applied in various fields. Therefore, hAMSCs represent a promising candidate to facilitate cartilage regeneration. Nonetheless, no studies have investigated the application of hAMSC sheets to repair cartilage defects in vivo. Purpose: To evaluate hAMSC sheets encapsulating cartilage particles to promote repair of rabbit osteochondral defects. Study Design: Controlled laboratory study. Methods: hAMSC sheets were constructed with passage 3 hAMSCs. The phenotypic and structural characteristics of hAMSC sheets were evaluated by flow cytometry and scanning electron microscopy, respectively. The potential for chondrogenic differentiation of hAMSC sheets was assessed by cartilage-specific marker staining, immunohistochemistry, and mRNA and protein expression (SOX9, COLII, and ACAN). Osteochondral defects (diameter, 3.5 mm; depth, 3 mm) were created in the left patellar grooves of 20 New Zealand White rabbits (female or male). The defects were treated with hAMSC sheet/cartilage particles (n = 5), cartilage particles (n = 5), hAMSC sheets (n = 5), or fibrin glue (n = 5). Macroscopic and histological evaluations of the regenerated tissue were conducted after 3 months. The survival time and differentiation of transplanted hAMSCs in the defect area were evaluated by immunofluorescence. Results: hAMSC sheets had a multilayered structure, with cells stacked layer by layer. Importantly, hAMSC sheets highly expressed phenotypic markers of mesenchymal stem cells. Cartilage-specific marker staining and immunohistochemistry were positive, and mRNA and protein expression was higher in the chondrogenically induced hAMSC sheet group than in the hAMSC sheet group (P <.05). hAMSC sheet/cartilage particles formed a large amount of hyaline-like cartilage in the defect area. In addition, macroscopic and histological scores were significantly higher than those in the other groups. Integration with surrounding normal cartilage and subchondral bone regeneration in the hAMSC sheet/cartilage particles group were better when compared with the other groups. A large number of human nuclear-specific antigen-positive cells were observed in the defect area of hAMSC sheet/cartilage particles and hAMSC sheet groups. Moreover, some positive cells expressed SOX9. Conclusion: hAMSC sheets encapsulating cartilage particles facilitate osteochondral defect repair. Clinical Relevance: Delivery of cells in the form of a cell sheet in conjunction with cartilage particles provides a novel approach for cell-based cartilage regeneration. [ABSTRACT FROM AUTHOR]

Aim: An attempt was made to improve osteochondral healing with allogeneic mesenchymal stem cells (MSCs) along with certain growth factors. Materials & methods: Induced knee osteochondral defects were filled as: phosphate buffer saline (group A); MSCs in collagen gel (group B); group B plus insulin like growth factor-1 (group C); group C plus transforming growth factor β-1 (group D). Results: Gross and scanning electron microscopy showed superior morphology and surface architecture of the healed tissue in groups D and C. Histologically, group D revealed hyaline cartilage characteristic features followed in order by group C and group B. In all treatment groups, chondrogenic matrix, collagen II2B (col II 2B) and aggrecan were secreted. Conclusion: Combined use of MSCs and growth factors could accelerate osteochondral healing. [ABSTRACT FROM AUTHOR]

Background: The treatment of osteochondral defects (OCDs) constitutes a major problem for orthopaedic surgeons. The altered mechanics and the cell types, with associated soluble factors derived from the exposed subchondral bone, are likely responsible for the mechanically and structurally inferior articular cartilage subsequently obtained as a repair tissue. There is therefore an unmet clinical need for bioresponsive biomaterials that allow cell delivery, reduce cell infiltration from the bone marrow, and support chondrogenesis in the presence of joint mechanical loading. Purpose: To develop a cell-laden injectable biomaterial, with bioadhesive properties, low cell invasion, and good mechanoresilience, in which simulated joint loading could induce tissue maturation through the production and activation of transforming growth factor beta 1 (TGF-β1). Study Design: Controlled laboratory study. Methods: Human bone marrow–derived mesenchymal stromal/stem cells were encapsulated in tyramine-modified hyaluronic acid (HA-Tyr) hydrogels, with crosslinking initiated by the addition of horseradish peroxidase (HRP) and various concentrations of hydrogen peroxide (H2O2; 0.3-2 mM). Cytocompatibility and biomechanical and adhesive properties were analyzed by live/dead staining, rheology, and push-out test, respectively. For multiaxial loading, cell-laden hydrogels were subjected to 10% compression superimposed onto a 0.5-N preload and shear loading (±25°) at 1 Hz for 1 hour per day and 5 times a week for 4 weeks. TGF-β1 production and activation were measured by enzyme-linked immunosorbent assay (ELISA). Results: The viscoelastic properties of the cell-laden HA-Tyr hydrogels, as crosslinked with different ratios of HRP and H2O2, were demonstrated for a range of cell densities and HRP/H2O2 concentrations. In the absence of serum supplementation, cell invasion into HA-Tyr hydrogels was minimal to absent. The bonding strength of HA-Tyr to articular cartilage compared favorably with clinically used fibrin gel. Conclusion: HA-Tyr hydrogels can be mechanically conditioned to induce activation of endogenous TGF-b1 produced by the embedded cells. HA-Tyr hydrogels function as cell carriers supporting biomechanically induced production and activation of TGF-β1 and as bioadhesive materials with low cell invasion, suggesting that they hold promise as a novel biomaterial for OCD repair strategies. Clinical Relevance: Leveraging physiological joint mechanics to support chondrogenic graft maturation in an optimized mechanosensitive hydrogel in the absence of exogenous growth factors is of highest interest for OCD repair. [ABSTRACT FROM AUTHOR]

Purpose: The treatment of osteochondral defects in joint cartilage remains challenging due to its limited repair capacity. This study presents a metallic osteochondral plug with hydroxyapatite (HA)-coated cap edges for improved implant-tissue contact. The hypothesis was that improved attachment prevents from synovial fluid-influx and thereby avoids osteolysis and resulting implant instability.Methods: In total, 24 female, adult sheep were randomized into three groups. All animals received an Episealer®-implant in the medial condyle of the right knee. The implants were coated with two different HA versions or uncoated (control group). After 12 weeks, the implant-tissue connections were analysed radiologically and histologically.Results: In general, the groups with the coated cap edges showed a better quality of tissue connection to the implant. The occurrence of gaps between tissue and implant was more seldom, the binding of calcified and hyaline cartilage to the cap was significantly better than in the uncoated group. A histomorphometrically measured lower amount of void space in these groups compared to the group with the uncoated edges confirmed that.Conclusions: The hypothesis of a tighter cartilage bone contact was confirmed. The HA coating of the implant's cap edges resulted in better adherence of cartilage to the implant, which was not previously reported. In conclusion, this led to a better contact between implant and cartilage as well as neighbouring bone. In clinical routine, joint fluid is aggressive, penetrates through cartilage rifts, and promotes osteolysis and loosening of implants. The observed sealing effect will act to prevent joint fluid to get access to the implant-tissue interfaces. Joint fluid is aggressive, can cause osteolysis, and can, clinically cause pain. These effects are liable to decrease with these findings and will further the longevity of these osteochondral implants. [ABSTRACT FROM AUTHOR]

Background: Recruitment of endogenous stem cells has been considered an alternative to cell injection/implantation in articular cartilage repair. Purpose: (1) To develop a cartilage tissue-engineering scaffold with clinically available biomaterials and functionalize the scaffold with an aptamer (Apt19s) that specifically recognizes pluripotent stem cells. (2) To determine whether this scaffold could recruit joint-resident mesenchymal stem cells (MSCs) when implanted into an osteochondral defect in a rabbit model and to examine the effects of cartilage regeneration. Study Design: Controlled laboratory study. Methods: The reinforced scaffold was fabricated by embedding a silk fibroin sponge into silk fibroin/hyaluronic acid–tyramine hydrogel and characterized in vitro. A cylindrical osteochondral defect (3.2 mm wide × 4 mm deep) was created in the trochlear grooves of rabbit knees. The rabbits were randomly assigned into 3 groups: Apt19s-functionalized scaffold group, scaffold-only group, and control group. Animals were sacrificed at 6 and 12 weeks after transplantation. Repaired tissues were evaluated via gross examination, histologic examination, and immunohistochemistry. Results: In vitro, this aptamer-functionalized scaffold could recruit bone marrow–derived MSCs and support cell adhesion. In vivo, the aptamer-functionalized scaffold enhanced cell homing in comparison with the aptamer-free scaffold. The aptamer-functionalized scaffold group also exhibited superior cartilage restoration when compared with the scaffold-only group and the control group. Conclusion: The Apt19s-functionalized scaffold exhibited the ability to recruit MSCs both in vitro and in vivo and achieved a better outcome of cartilage repair than the scaffold only or control in an osteochondral defect model. Clinical Relevance: The findings demonstrate a promising strategy of using aptamer-functionalized bioscaffolds for restoration of chondral/osteochondral defects via aptamer-introduced homing of MSCs. [ABSTRACT FROM AUTHOR]

Background: Osteochondral allograft transplantation (OCA) is a successful knee joint preservation technique; however, the effects of defect size and defect size:condyle ratio (DSCR) are poorly understood. Purpose: To quantify clinical outcomes of isolated OCA of the knee based on defect size and DSCR. Study Design: Cohort study; Level of evidence, 3. Methods: Data from patients who underwent OCA of the knee without major concomitant procedures by a single surgeon were analyzed at a minimum follow-up of 2 years. Osteochondral defect size was measured intraoperatively, and femoral condyle size was measured with preoperative imaging. Patient-reported outcomes, reoperations, and survival rates were analyzed per defect size and DSCR, comparing males and females and patients <40 and ≥40 years old. Results: Sixty-eight patients were included, of whom 57% were male (mean ± SD: age, 34.5 ± 10.3 years; follow-up, 5.2 ± 2.6 years). Mean osteochondral defect size and DSCR were 3.48 ± 1.72 cm2 and 0.2 ± 0.1, respectively. Defect size was larger among males as compared with females (3.97 ± 1.71 cm2 vs 2.81 ± 1.16 cm2, P =.005), while DSCRs were not significantly different between sexes (P =.609). The cohort as a whole demonstrated improvements in the following scores: Lysholm, International Knee Documentation Committee, Knee injury and Osteoarthritis Outcome Score, Western Ontario and McMaster Universities Osteoarthritis Index, and 12-Item Short Form Health Survey Physical (P <.05). There were 27 reoperations (39.7%) at a mean of 2.5 ± 1.92 years and 8 failures (11.8%) at a mean of 2.62 ± 1.3 years. Mean DCSR was higher among patients with graft failure (0.26 ± 0.20 vs 0.19 ± 0.07, P =.049). After stratification by age, failures among patients ≥40 years old were associated with a larger defect size (mean 5.37 ± 3.50 cm2 vs 3.22 ± 1.32 cm2, P =.03) and higher DSCR (mean 0.30 ± 0.25 vs 0.19 ± 0.06, P =.05) when compared with nonfailures. Failures among patients <40 years old were not significantly associated with defect size or DSCR (P >.05) as compared with nonfailures. Conclusion: Patients undergoing isolated OCA transplantation demonstrated significant clinical improvements and a graft survival of 88.2% at 5.2 years. Failures overall were associated with a larger DSCR, and failures among patients ≥40 years old with a larger DSCR and larger defect size. Increasing defect size among males was positively correlated with some improved outcomes, although this was not maintained in analysis of the DSCR, suggesting similar prognosis after OCA regardless of sex. Clinical Relevance: Failed osteochondral allografts are associated with larger defect sizes and defect:condyle ratios in this study, providing additional information to surgeons for appropriate patient consultation. [ABSTRACT FROM AUTHOR]

Abstract A significant number of patients suffer from focal articular damage that is neither appropriate for traditional arthroplasty, nor for biological repair. Since 2005, contoured focal resurfacing systems for the femoral condyle have been available that can cater for this specific subgroup of patients. Independent long-term data on these implants have previously been lacking, but are now becoming available. This review will look at: the basic biology of cartilage, the natural progression of focal cartilage disease in the knee, the surgical and non-surgical options available, the indications for focal resurfacing, surgical techniques, which implants are currently available, and the current clinical data with respect to these. [ABSTRACT FROM AUTHOR]

Purpose: The patellofemoral (PF) joint contains the thickest articular cartilage in the human body. Chondral lesions to this area are often misdiagnosed and can predispose to secondary osteoarthritis if left untreated. Treatment options range from arthroscopic debridement to cartilage restoration techniques such as microfracture (MFx), autologous chondrocyte implantation (ACI), and osteochondral autograft transplantation. The purpose of this study was to systematically assess the trends in surgical techniques, outcomes, and complications of cartilage restoration of the PF joint.Methods: This review has been conducted according to the guidelines of Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA). The electronic databases PubMed, MEDLINE, and EMBASE were searched from January 1, 2007 to April 30, 2018. The Methodological Index for Non-randomized Studies (MINORS) was used to assess study quality. A two-proportion z test was used to determine whether the differences between the proportions of cartilage restoration techniques used from 2007 to 2012 and 2013-2018 were statistically significant.Results: Overall, 28 studies were identified, including 708 patients (824 knees) with a mean age of 39.5 ± 10.5 years and a mean follow-up of 39.1 ± 16.0 months. Majority of patients were treated with ACI (45.5%) and MFx (29.6%). A significant increase in the use of the third generation ACI occurred with a simultaneous decreased usage of the conventional MFx over the last 5 years (p < 0.001). All techniques had significant (p < 0.05) improvements in clinical outcomes. The overall complication rate was 9.2%, of which graft hypertrophy (2.7%) was the most prevalent.Conclusions: ACI was the most common restoration technique. The use of third generation ACI has increased with a concurrent decline in the use of conventional MFx over the latter half of the past decade (p < 0.001). Overall, the various cartilage restoration techniques reported improvements in patient reported outcomes with low complication rates. Definitive conclusions on the optimal treatment remain elusive due to a lack of high-quality comparative studies.Level Of Evidence: Level IV, Systematic Review of Level-II-IV studies. [ABSTRACT FROM AUTHOR]

Abstract Biological scaffolds generated from tissue-derived extracellular matrix (ECM) are commonly used clinically for soft tissue regeneration. Such biomaterials can enhance tissue-specific differentiation of adult stem cells, suggesting that structuring different ECMs into multi-layered scaffolds can form the basis of new strategies for regenerating damaged interfacial tissues such as the osteochondral unit. In this study, mass spectrometry is used to demonstrate that growth plate (GP) and articular cartilage (AC) ECMs contain a unique array of regulatory proteins that may be particularly suited to bone and cartilage repair respectively. Applying a novel iterative freeze-drying method, porous bi-phasic scaffolds composed of GP ECM overlaid by AC ECM are fabricated, which are capable of spatially directing stem cell differentiation in vitro , promoting the development of graded tissues transitioning from calcified cartilage to hyaline-like cartilage. Evaluating repair 12-months post-implantation into critically-sized caprine osteochondral defects reveals that these scaffolds promote regeneration in a manner distinct to commercial control-scaffolds. The GP layer supports endochondral bone formation, while the AC layer stimulates the formation of an overlying layer of hyaline cartilage with a collagen fiber architecture better recapitulating the native tissue. These findings support the use of a bi-layered, tissue-specific ECM derived scaffolds for regenerating spatially complex musculoskeletal tissues. Graphical abstract Image 1 [ABSTRACT FROM AUTHOR]

Objective: To investigate whether T2 relaxation time measurements of cartilage repair tissue and structural changes of the knee joint are associated with subchondral bone architecture after spongiosa-augmented matrix-associated autologous chondrocyte implantation (MACI).Design: Both knees of 25 patients (25.5 ± 7.8y; 10 women) were examined preoperatively and 2.7 years after unilateral spongiosa-augmented MACI with 3T magnetic resonance (MR) imaging. Cartilage composition was assessed using T2 relaxation time measurements, subchondral trabecular bone microstructure was quantified using a 3D phase-cycled balanced steady state free-precision sequence. Structural knee joint changes were assessed using the modified Whole-Organ Magnetic Resonance Imaging Score (WORMS). The Magnetic Resonance Observation of Cartilage Repair Tissue (MOCART) score was used for the postoperative description of the area that underwent MACI. Correlations were assessed using Spearman's rank correlation coefficients.Results: Hypertrophy of the cartilage repair tissue was found in 2 of 25 patients, both after a MACI procedure at the patella, 21 patients showed congruent filling. In subchondral bone of the cartilage repair compartment, apparent trabecular thickness was significantly higher in compartments with elevated cartilage T2 (n = 17; 0.37 ± 0.05 mm) compared to those showing no difference in cartilage T2 compared to the same compartment in the contralateral knee (n = 8; 0.27 ± 0.05 mm; P = 0.042). Significant correlations were found between the overall progression of WORMS and the ipsilateral vs contralateral ratio of average trabecular thickness (r = 0.48, P = 0.031) and bone fraction (r = 0.57, P = 0.007).Conclusions: After spongiosa-augmented MACI, T2 values of cartilage repair tissue and structural knee joint changes correlated with the quality of the underlying trabecular bone. [ABSTRACT FROM AUTHOR]