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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: Limitations to using the knee as donor cartilage include cartilage thickness mismatch and donor site morbidity. Using the radial head as donor autograft for capitellar lesions may allow for local graft harvest without distant donor site morbidity. The purpose of this study is to demonstrate the feasibility of performing local osteochondral autograft transfer from the nonarticular cartilaginous rim of the radial head to the capitellum. Additionally, we sought to determine the load to failure of the radial head after harvest. Methods: Sixteen matched cadaveric elbows were used. A Kaplan approach was performed in half of the specimens and an extensor digitorum communis split in the other half. 6-mm and 8-mm capitellar cartilage defects were created. A donor plug was harvested from the rim of the radial head and transferred to the capitellum. In half of the specimens, the donor site was backfilled with autograft from the recipient plug. The other half was backfilled with calcium phosphate cement. The radial head was removed from the specimen and biomechanical analysis performed. Results: Both surgical approaches had adequate exposure to access the lateral two-third capitellar lesions in all specimens. The medial third of the capitellum was less accessible in extensor digitorum communis split approaches (1/8) compared to the Kaplan approach (6/8; P = .01). The average cartilage thickness of the peripheral rim of the radial head and capitellum was 2.5 mm (range 1.8-3.2, standard deviation 0.4) and 2.2 mm (range 1.8-3, standard deviation 0.3), respectively. During the procedure, 2 of 8 radial heads fractured in the 8-mm plug group. No radial heads fractured in the 6-mm group (P = .47). Biomechanical testing demonstrated a mean load to failure of 1993N with no difference between groups when stratified by donor plug size or type of backfill. Conclusion: This study demonstrates that the nonarticulating peripheral cartilaginous rim of the radial head could be a local harvest site for osteochondral autograft transfer for capitellar lesions up to 8 mm in diameter. The cartilage thickness of the radial head closely approximates the capitellum. Biomechanical analysis did not demonstrate a significant difference in load to fracture when backfilling the radial head harvest site with autograft bone or calcium phosphate cement. After harvest, the radial head could withstand forces much greater than those seen across the elbow when nonweight-bearing. Further investigation is needed to determine how to mitigate the risk of iatrogenic fracture with this operation.

Abstract 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

This study reported the biological changes occurring after γ-irradiation of in vivo rat model and the osteochondral protective effect of Gelatine-Chitosan-Ginger (GEL-CH-GING). The results showed that Electron Paramagnetic Resonance (EPR) Spectroscopy of GEL-CH-GING showed two paramagnetic centres which correspond to g=2.19 and g= 2.002. The Fourier transform infrared spectroscopy (FTIR) analyses revealed an increase in peak intensity at C–H chains, as well as, C=O carbonyl groups. The X-ray diffraction (XRD) analysis showed no change of crystallinity. After gamma ray exposure, the rat groups have received an osteochondral defect and then were treated with GEL-CH-GING composite. Sixty days post-surgery, a significant reduction in thiobarbituric acid-reactive compounds (TBARs) was seen when compared to non-implanted rat group. Concerning oxidative stress status, GEL-CH-GIN significantly improved Superoxide Dismutase (SOD) 76 nmol/l, Catalase (CAT) 0.79 nmol/l, and Glutathione Peroxidase (GPx) 1.77 nmol/l activities in osteochondral tissue. Regarding the histomorphometric parameters of cartilaginous tissue (nCg.Th, µm), (cCg.Th, µm), (Cg.Th, µm), irradiated-GEL-CH-GIN group showed a significant increase as compared to irradiated group with 116, 74 and 188 µm, respectively (p

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]

BACKGROUND: A large number of studies have confirmed that tissue engineering scaffolds can almost completely repair osteochondral defects. However, when osteochondral defects are complicated with infection, even after thorough debridement in the early stage, the repair effect of simple osteochondral tissue engineering scaffolds is often unsatisfactory. OBJECTIVE: To prepare fibroin/chitosan/nano-hydroxyapatite scaffold loaded with vancomycin hydrochloride sustained release microspheres, and to investigate the repair effect on infected osteochondral defect in distal femur of rabbit. METHODS: (1) Vancomycin hydrochloride sustained release microspheres were prepared by emulsified solvent evaporation method. The sustained-release microspheres of different weights (7.5, 10, and 12.5 mg) were mixed with fibroin protein-chitosan nanohydroxyapatite solution, and the scaffolds of fibroin protein/chitosan/nano-hydroxyapatite were prepared by chemical crosslinking method. The porosity, water absorption and expansion rate, hot water loss rate of the scaffolds, and drug sustained-release in vitro were characterized. (2) Forty-five New Zealand white rabbits were randomly divided into blank group, control group, and experimental group, with 15 rabbits in each group. The osteochondral defect and infection model of the distal femur of the right hind limb was established in both groups. The blank group was not treated, and the control group was implanted with fibroin protein-chitosan-nano-hydroxyapatite scaffold. Vancomycin hydrochloride sustained-release microspheres (10 mg) of fibroin/chitosan/nano-hydroxyapatite scaffold were implanted in the defect of the experimental group. The levels of C-reactive protein and leukocytes in blood samples were detected 1 week after operation. At 4, 8 and 12 weeks after operation, the tissue of the operative area was taken for gross observation and pathological observation. RESULTS AND CONCLUSION: (1) With the increase of sustained-release microspheres content, the porosity of scaffolds decreased, and there was significant difference among groups (P < 0.05). There were no significant differences in the pore size, water absorption expansion rate and hot water loss rate among the three groups (P > 0.05). Vancomycin hydrochloride was released sustainably in vitro for more than 30 days in all three groups of scaffolds. (2) The levels of C-reactive protein and leukocytes in blood samples of the experimental group were lower than those of the blank group and control group (P < 0.05). The repair of gross cartilage in the experimental group was significantly better than that in the blank group and the control group. Hematoxylin-eosin, Masson, Alcian blue and type II collagen immunohistochemical stainings showed that the osteochondral repair effect of the experimental group was significantly better than that of the blank group and the control group at each time point. (3) The results showed that fibroin/chitosan/nano-hydroxyapatite scaffolds loaded with vancomycin hydrochloride sustained-release microspheres could effectively promote the repair of open osteochondral defects. [ABSTRACT FROM AUTHOR]

Osteochondral defects (OCD) are a focal pathology affecting the sub-chondral bone and overlying cartilage. The presence of Osteochondral defects (OCD) within the foot and ankle are well established. Despite this, they are often regarded as an insidious finding, prone to misdiagnosis which can result in significant debilitation to the affected individual. The mechanisms underlying the formation of these lesions remain disputed. Moreover, the incidence of isolated Osteochondral defects affecting the first Metatarsophalangeal joint in the absence of any additional pathology is unknown.There are a range of surgical treatment modalities described to treat Osteochondral defects. Strategies typically involve cartilage regeneration or replacement of the articular surface: however there are no consensus guidelines regarding the optimum surgical management when applied to the first Metatarsophalangeal joint. The following concepts review aims to explore the literature pertaining to the surgical management of Osteochondral defects including an innovative approach case study employing subchondral drilling technique.Osteochondral defects are managed with a variety of surgical procedures. Surgical outcomes are often derived from literature relating to the knee and hindfoot with little or no study on the forefoot. The included case study demonstrates positive patient satisfaction (PSQ-10) score, improved foot function (MOXFQ) and pain reduction with a novel antegraded Osteochondral drilling technique when applied to the first metatarsal. Further study into the application of contemporary cartilage regeneration and replacement strategies in this location is warranted.

Aims: To explore the efficacy of extracorporeal shockwave therapy (ESWT) in the treatment of osteochondral defect (OCD), and its effects on the levels of transforming growth factor (TGF)-β, bone morphogenetic protein (BMP)-2, -3, -4, -5, and -7 in terms of cartilage and bone regeneration. Methods: The OCD lesion was created on the trochlear groove of left articular cartilage of femur per rat (40 rats in total). The experimental groups were Sham, OCD, and ESWT (0.25 mJ/mm2, 800 impulses, 4 Hz). The animals were euthanized at 2, 4, 8, and 12 weeks post-treatment, and histopathological analysis, micro-CT scanning, and immunohistochemical staining were performed for the specimens. Results: In the histopathological analysis, the macro-morphological grading scale showed a significant increase, while the histological score and cartilage repair scale of ESWT exhibited a significant decrease compared to OCD at the 8- and 12-week timepoints. At the 12-week follow-up, ESWT exhibited a significant improvement in the volume of damaged bone compared to OCD. Furthermore, immunohistochemistry analysis revealed a significant decrease in type I collagen and a significant increase in type II collagen within the newly formed hyaline cartilage following ESWT, compared to OCD. Finally, SRY-box transcription factor 9 (SOX9), aggrecan, and TGF-β, BMP-2, -3, -4, -5, and -7 were significantly higher in ESWT than in OCD at 12 weeks. Conclusion: ESWT promoted the effect of TGF-β/BMPs, thereby modulating the production of extracellular matrix proteins and transcription factor involved in the regeneration of articular cartilage and subchondral bone in an OCD rat model. Cite this article: Bone Joint Res 2024;13(7):342–352.

Abstract Bioactive agents have demonstrated regenerative potential for cell-free bone tissue engineering. Nevertheless, certain challenges persist, including ineffective delivery methods and confined therapeutic potency. Here, we demonstrated that the biomimetic calcium phosphate coating system (BioCaP) could effectively uptake and slowly release the incorporated bioactive agents compared to the surface absorption system via osteoclast-mediated degradation of BioCaP coatings. The release kinetics were determined as a function of time. The release rate was stable without remarkable burst release during the first 1 day, followed by a sustained release from day 7 to day 19. Then, we developed the bi-functional BioCaP-coated silk fibroin scaffolds enabling the effective co-delivery of TGF-β3 and BMP-2 (SFI-T/SFI-B) and the corresponding slow release of TGF-β3 and BMP-2 exhibited superior potential in promoting chondrogenesis and osteogenesis without impairing cell vitality in vitro. The SFI-T/SFI-B scaffolds could improve cartilage and bone regeneration in 5 × 4 mm rabbit osteochondral (OC) defect. These findings indicate that the biomimetic calcium-phosphate coated silk fibroin scaffolds with slowly co-released TGF-β3 and BMP-2 effectively promote the repair of OC defects, hence facilitating the future clinical translation of controlled drug delivery in tissue engineering. Graphic Abstract

Background: Osteochondral regeneration has long been recognized as a complex and challenging project in the field of tissue engineering. In particular, reconstructing the osteochondral interface is crucial for determining the effectiveness of the repair. Although several artificial layered or gradient scaffolds have been developed recently to simulate the natural interface, the functions of this unique structure have still not been fully replicated. In this paper, we utilized laser micro-patterning technology (LMPT) to modify the natural osteochondral “plugs” for use as grafts and aimed to directly apply the functional interface unit to repair osteochondral defects in a goat model. Methods: For in vitro evaluations, the optimal combination of LMPT parameters was confirmed through mechanical testing, finite element analysis, and comparing decellularization efficiency. The structural and biological properties of the laser micro-patterned osteochondral implants (LMP-OI) were verified by measuring the permeability of the interface and assessing the recellularization processes. In the goat model for osteochondral regeneration, a conical frustum-shaped defect was specifically created in the weight-bearing area of femoral condyles using a customized trephine with a variable diameter. This unreported defect shape enabled the implant to properly self-fix as expected. Results: The micro-patterning with the suitable pore density and morphology increased the permeability of the LMP-OIs, accelerated decellularization, maintained mechanical stability, and provided two relative independent microenvironments for subsequent recellularization. The LMP-OIs with goat's autologous bone marrow stromal cells in the cartilage layer have securely integrated into the osteochondral defects. At 6 and 12 months after implantation, both imaging and histological assessments showed a significant improvement in the healing of the cartilage and subchondral bone. Conclusion: With the natural interface unit and zonal recellularization, the LMP-OI is an ideal scaffold to repair osteochondral defects especially in large animals. The translational potential of this article: These findings suggest that such a modified xenogeneic osteochondral implant could potentially be explored in clinical translation for treatment of osteochondral injuries. Furthermore, trimming a conical frustum shape to the defect region, especially for large-sized defects, may be an effective way to achieve self-fixing for the implant.

The bidirectional relationship between osteochondral defects (OCD) and osteoarthritis (OA), with each condition exacerbating the other, makes OCD regeneration in the presence of OA challenging. Type II collagen (Col2) is important in OCD regeneration and the management of OA, but its potential applications in cartilage tissue engineering are significantly limited. This study investigated the regeneration capacity of Col2 scaffolds in critical-sized OCDs under surgically induced OA conditions and explored the underlying mechanisms that promoted OCD regeneration. Furthermore, the repair potential of Col2 scaffolds was validated in over critical-sized OCD models. After 90 days or 150 days since scaffold implantation, complete healing was observed histologically in critical-sized OCD, evidenced by the excellent integration with surrounding native tissues. The newly formed tissue biochemically resembled adjacent natural tissue and exhibited comparable biomechanical properties. The regenerated OA tissue demonstrated lower expression of genes associated with cartilage degradation than native OA tissue but comparable expression of genes related to osteochondral anabolism compared with normal tissue. Additionally, transcriptome and proteome analysis revealed the hindrance of TGF-β-Smad1/5/8 in regenerated OA tissue. In conclusion, the engrafting of Col2 scaffolds led to the successful regeneration of critical-sized OCDs under surgically induced OA conditions by inhibiting the TGF-β-Smad1/5/8 signaling pathway.

Bioactive agents have demonstrated regenerative potential for cell-free bone tissue engineering. Nevertheless, certain challenges persist, including ineffective delivery methods and confined therapeutic potency. Here, we demonstrated that the biomimetic calcium phosphate coating system (BioCaP) could effectively uptake and slowly release the incorporated bioactive agents compared to the surface absorption system via osteoclast-mediated degradation of BioCaP coatings. The release kinetics were determined as a function of time. The release rate was stable without remarkable burst release during the first 1 day, followed by a sustained release from day 7 to day 19. Then, we developed the bi-functional BioCaP-coated silk fibroin scaffolds enabling the effective co-delivery of TGF-β3 and BMP-2 (SFI-T/SFI-B) and the corresponding slow release of TGF-β3 and BMP-2 exhibited superior potential in promoting chondrogenesis and osteogenesis without impairing cell vitality in vitro. The SFI-T/SFI-B scaffolds could improve cartilage and bone regeneration in 5 × 4 mm rabbit osteochondral (OC) defect. These findings indicate that the biomimetic calcium-phosphate coated silk fibroin scaffolds with slowly co-released TGF-β3 and BMP-2 effectively promote the repair of OC defects, hence facilitating the future clinical translation of controlled drug delivery in tissue engineering. [ABSTRACT FROM AUTHOR]

Here, we describe a case of a 5-year-old show-jumping stallion presented with severe lameness, swelling, and pain on palpation of the left metacarpophalangeal joint (MCj). Diagnostic imaging revealed full and partial-thickness articular defects over the lateral condyle of the third metacarpus (MC3) and the dorsolateral aspect of the first phalanx (P1). After the lesion's arthroscopic curettage, the patient was subjected to an innovative regenerative treatment consisting of two intra-articular injections of equine synovial membrane mesenchymal stem/stromal cells (eSM-MSCs) combined with umbilical cord mesenchymal stem/stromal cells conditioned medium (UC-MSC CM), 15 days apart. A 12-week rehabilitation program was accomplished, and lameness, pain, and joint effusion were remarkably reduced; however, magnetic resonance imaging (MRI) and computed tomography (CT) scan presented incomplete healing of the MC3's lesion, prompting a second round of treatment. Subsequently, the horse achieved clinical soundness and returned to a higher level of athletic performance, and imaging exams revealed the absence of lesions at P1, fulfillment of the osteochondral lesion, and cartilage-like tissue formation at MC3's lesion site. The positive outcomes suggest the effectiveness of this combination for treating full and partial cartilage defects in horses. Multipotent mesenchymal stem/stromal cells (MSCs) and their bioactive factors compose a novel therapeutic approach for tissue regeneration and organ function restoration with anti-inflammatory and pro-regenerative impact through paracrine mechanisms. [ABSTRACT FROM AUTHOR]

Background: Dorsoproximal osteochondral defects commonly affect the proximal phalanx, but information about diagnosis on computed tomography (CT) and magnetic resonance imaging (MRI) is limited. Objectives: To assess CT and MRI diagnoses of osteochondral defects, describe the lesions and compare sensitivity and specificity of the modalities using macroscopic pathology as gold standard. Study design: Cross‐sectional study. Methods: Thirty‐five equine cadaver limbs underwent standing cone‐beam CT (CBCT), fan‐beam CT (FBCT), low‐field MRI and pathological examination. CT and MR images were examined for proximal phalanx dorsomedial and dorsolateral eminence osteochondral defects. Defect dimensions were measured. Imaging diagnoses and measurements were compared with macroscopic examination. Results: Fifty‐six defects were seen over 70 potential locations. On CBCT and FBCT, osteochondral defects appeared as subchondral irregularity/saucer‐shaped defects. On MRI, osteochondral defects were a combination of articular cartilage defect on dorsal images and subchondral flattening/irregularity on sagittal images. Subchondral thickening and osseous short tau inversion recovery hyperintensity were found concurrent with osteochondral defects. Compared with pathological examination, the sensitivity and specificity of diagnosis were 86% (95% confidence interval [95% CI] 75%–93%) and 64% (95% CI 38%–85%) for FBCT; 64% (95% CI 51%–76%) and 71% (95% CI 46%–90%) for CBCT; and 52% (95% CI 39%–65%) and 71% (95% CI 46%–90%) for MRI. Sensitivity of all modalities increased with defect size. Macroscopic defect dimensions were strongly correlated with CBCT (r = 0.76, p < 0.001) and moderately correlated with FBCT and MRI (r = 0.65, p < 0.001). Macroscopic measurements were significantly greater than all imaging modality dimensions (p < 0.001), potentially because macroscopy included articular cartilage pathology. Main limitations: Influence of motion artefact could not be assessed. Conclusions: Osteochondral defects could be visualised using both CT and MRI with sensitivity increasing with defect size. Diagnostic performance was best using FBCT, followed by CBCT then MRI, but CBCT‐measured defect size best correlated with macroscopic examination. MRI provided useful information on fluid signal associated with defects, which could represent active pathology. [ABSTRACT FROM AUTHOR]

Background: Cartilage tissue engineering faces challenges related to the use of scaffolds and limited seed cells. This study aims to propose a cost-effective and straightforward approach using costal chondrocytes (CCs) as an alternative cell source to overcome these challenges, eliminating the need for special culture equipment or scaffolds. Methods: CCs were cultured at a high cell density with and without ascorbic acid treatment, serving as the experimental and control groups, respectively. Viability and tissue-engineered constructs (TEC) formation were evaluated until day 14. Slices of TEC samples were used for histological staining to evaluate the secretion of glycosaminoglycans and different types of collagen proteins within the extracellular matrix. mRNA sequencing and qPCR were performed to examine gene expression related to cartilage matrix secretion in the chondrocytes. In vivo experiments were conducted by implanting TECs from different groups into the defect site, followed by sample collection after 12 weeks for histological staining and scoring to evaluate the extent of cartilage regeneration. Hematoxylin-eosin (HE), Safranin-O-Fast Green, and Masson's trichrome stainings were used to examine the content of cartilage-related matrix components in the in vivo repair tissue. Immunohistochemical staining for type I and type II collagen, as well as aggrecan, was performed to assess the presence and distribution of these specific markers. Additionally, immunohistochemical staining for type X collagen was used to observe any hypertrophic changes in the repaired tissue. Results: Viability of the chondrocytes remained high throughout the culture period, and the TECs displayed an enriched extracellular matrix suitable for surgical procedures. In vitro study revealed glycosaminoglycan and type II collagen production in both groups of TEC, while the TEC matrix treated with ascorbic acid displayed greater abundance. The results of mRNA sequencing and qPCR showed that genes related to cartilage matrix secretion such as Sox9, Col2, and Acan were upregulated by ascorbic acid in costal chondrocytes. Although the addition of Asc-2P led to an increase in COL10 expression according to qPCR and RNA-seq results, the immunofluorescence staining results of the two groups of TECs exhibited similar distribution and fluorescence intensity. In vivo experiments showed that both groups of TEC could adhere to the defect sites and kept hyaline cartilage morphology until 12 weeks. TEC treated with ascorbic acid showed superior cartilage regeneration as evidenced by significantly higher ICRS and O'Driscoll scores and stronger Safranin-O and collagen staining mimicking native cartilage when compared to other groups. In addition, the immunohistochemical staining results of Collgan X indicated that, after 12 weeks, the ascorbic acid-treated TEC did not exhibit further hypertrophy upon transplantation into the defect site, but maintained an expression profile similar to untreated TECs, while slightly higher than the sham-operated group. Conclusion: These results suggest that CC-derived scaffold-free TEC presents a promising method for articular cartilage regeneration. Ascorbic acid treatment enhances outcomes by promoting cartilage matrix production. This study provides valuable insights and potential advancements in the field of cartilage tissue engineering. The translational potential of this article: Cartilage tissue engineering is an area of research with immense clinical potential. The approach presented in this article offers a cost-effective and straightforward solution, which can minimize the complexity of cell culture and scaffold fabrication. This simplification could offer several translational advantages, such as ease of use, rapid scalability, lower costs, and the potential for patient-specific clinical translation. The use of costal chondrocytes, which are easily obtainable, and the scaffold-free approach, which does not require specialized equipment or membranes, could be particularly advantageous in clinical settings, allowing for in situ regeneration of cartilage.

Here, we describe a case of a 5-year-old show-jumping stallion presented with severe lameness, swelling, and pain on palpation of the left metacarpophalangeal joint (MCj). Diagnostic imaging revealed full and partial-thickness articular defects over the lateral condyle of the third metacarpus (MC3) and the dorsolateral aspect of the first phalanx (P1). After the lesion’s arthroscopic curettage, the patient was subjected to an innovative regenerative treatment consisting of two intra-articular injections of equine synovial membrane mesenchymal stem/stromal cells (eSM-MSCs) combined with umbilical cord mesenchymal stem/stromal cells conditioned medium (UC-MSC CM), 15 days apart. A 12-week rehabilitation program was accomplished, and lameness, pain, and joint effusion were remarkably reduced; however, magnetic resonance imaging (MRI) and computed tomography (CT) scan presented incomplete healing of the MC3’s lesion, prompting a second round of treatment. Subsequently, the horse achieved clinical soundness and returned to a higher level of athletic performance, and imaging exams revealed the absence of lesions at P1, fulfillment of the osteochondral lesion, and cartilage-like tissue formation at MC3’s lesion site. The positive outcomes suggest the effectiveness of this combination for treating full and partial cartilage defects in horses. Multipotent mesenchymal stem/stromal cells (MSCs) and their bioactive factors compose a novel therapeutic approach for tissue regeneration and organ function restoration with anti-inflammatory and pro-regenerative impact through paracrine mechanisms.

Osteochondral defect (OCD) is a common but challenging condition in orthopaedics that imposes huge socioeconomic burdens in our aging society. It is imperative to accelerate the R&D of regenerative scaffolds using osteochondral tissue engineering concepts. Yet, all innovative implant-based treatments require animal testing models to verify their feasibility, biosafety, and efficacy before proceeding to human trials. Rabbit models offer a more clinically relevant platform for studying OCD repair than smaller rodents, while being more cost-effective than large animal models. The core-decompression drilling technique to produce full-thickness distal medial femoral condyle defects in rabbits can mimic one of the trauma-relevant OCD models. This model is commonly used to evaluate the implant’s biosafety and efficacy of osteochondral dual-lineage regeneration. In this article, we initially indicate the methodology and describe a minimally-invasive surgical protocol in a step-wise manner to generate a standard and reproducible rabbit OCD for scaffold implantation. Besides, we provide a detailed procedure for sample collection, processing, and evaluation by a series of subsequent standardized biochemical, radiological, biomechanical, and histological assessments. In conclusion, the well-established, easy-handling, reproducible, and reliable rabbit OCD model will play a pivotal role in translational research of osteochondral tissue engineering.

Objective·To explore the role of advanced platelet-rich fibrin (A-PRF) in osteochondral regeneration.Methods·Bone-marrow mesenchymal stem cells (BMSCs) and knee joint chondrocytes were obtained from New Zealand rabbits. A-PRF was obtained by low-speed centrifugation of the heart blood of rabbits. The histological structure of A-PRF was observed by an optical microscope. The release of growth factors in A-PRF was detected by ELISA, including platelet-derived growth factor, transforming growth factor-β, insulin-like growth factor, vascular endothelial growth factor, epidermal growth factor and fibroblast growth factor. A-PRF's cytotoxicity and capability for promoting the proliferation of rabbit BMSCs were detected by live/dead double staining and MTT methods. The effect of A-PRF on the gene expression of type Ⅱ collagen, aggrecan, alkaline phosphatase (ALP) and osteocalcin (OCN) in rabbit BMSCs was detected by real-time fluorescence quantitative polymerase chain reaction (qRT-PCR). Transwell chambers were used to determine the effect of A-PRF on the migration ability of rabbit BMSCs and the chondrocytes. Rabbit knee osteochondral defect models were established, and 18 rabbits were randomly divided into 3 groups. The A-PRF group (n=6) was implanted with A-PRF in the defect, the A-PRF+BMSCs group (n=6) was implanted with rabbit BMSCs on A-PRF, and the control group (n=6) did not undergo implantation. The rabbits were sacrificed 12 weeks after surgery and the knee joint specimens were stained with hematoxylin-eosin (H-E), toluidine blue and safranin O/fast green. Based on the surface morphology and histology of the knee joints, the International Cartilage Repair Society (ICRS) scoring system was used for macroscopic and histological scoring.Results·A-PRF had a loose network structure and can slowly release growth factors. No cytotoxicity to rabbit BMSCs was observed after adding A-PRF, and the the capability for promoting the proliferation of rabbit BMSCs was significantly increased at 24, 48 and 72 h after adding A-PRF (all P

Background. The question of choosing a treatment strategy for full-thickness osteochondral defects of the tarsal bone remains relevant. When choosing a treatment strategy, two key points should be considered: restoring the architecture of the tarsal bone and achieving long-term restoration of cartilage-like coverage in the area of the osteochondral defect. Case report. A 34-year-old physically active patient sustained an ankle injury in 2011 and was treated conservatively. In 2020, he complained of pain and reduced activity. Initial assessment scores were: VAS (Visual Analog Scale) — 6 points, AOFAS-AHS (American Orthopaedic Foot and Ankle Society Ankle-Hindfoot Score) — 49 points, FAAM (Foot and Ankle Ability Measure) — 55 points. An MRI revealed an osteochondral defect in the medial part of the tarsal bone dome, measuring 16.4×9.4 mm and with a depth of 20.8 mm. The patient underwent the replacement of the bone defect with an autograft taken from the heel bone, using autologus matrix induced chondrogenesis (AMIC) procedure. After 6 months, a follow-up examination was performed, including ankle arthroscopy and removal of metal fixators. Arthroscopic findings showed that the chondroplasty area was almost identical to intact joint cartilage. One year after chondroplasty, the patient returned to his previous level of physical activity. Assessment scores were: VAS — 1 point, AOFAS-AHS — 94 points, FAAM — 83 points. Conclusion. The proposed method allows for the restoration of the architecture of the tarsal bone along with the cartilage surface. The use of a bone autograft helps to fill the tarsal bone defect, and covering the autograft with a collagen membrane contributes to the formation of hyaline-like cartilage tissue in the defect area.

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.

Osteochondral defect repair with a collagen/collagen-magnesium-hydroxyapatite (Col/Col-Mg-HAp) scaffold has demonstrated good clinical results. However, subchondral bone repair remained suboptimal, potentially leading to damage to the regenerated overlying neocartilage. This study aimed to improve the bone repair potential of this scaffold by incorporating newly developed strontium (Sr) ion enriched amorphous calcium phosphate (Sr-ACP) granules (100–150 μm). Sr concentration of Sr-ACP was determined with ICP-MS at 2.49 ± 0.04 wt%. Then 30 wt% ACP or Sr-ACP granules were integrated into the scaffold prototypes. The ACP or Sr-ACP granules were well embedded and distributed in the collagen matrix demonstrated by micro-CT and scanning electron microscopy/energy dispersive x-ray spectrometry. Good cytocompatibility of ACP/Sr-ACP granules and ACP/Sr-ACP enriched scaffolds was confirmed with in vitro cytotoxicity assays. An overall promising early tissue response and good biocompatibility of ACP and Sr-ACP enriched scaffolds were demonstrated in a subcutaneous mouse model. In a goat osteochondral defect model, significantly more bone was observed at 6 months with the treatment of Sr-ACP enriched scaffolds compared to scaffold-only, in particular in the weight-bearing femoral condyle subchondral bone defect. Overall, the incorporation of osteogenic Sr-ACP granules in Col/Col-Mg-HAp scaffolds showed to be a feasible and promising strategy to improve subchondral bone 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]

Objective·To explore the role of advanced platelet-rich fibrin (A-PRF) in osteochondral regeneration. Methods· Bone-marrow mesenchymal stem cells (BMSCs) and knee joint chondrocytes were obtained from New Zealand rabbits. A-PRF was obtained by low-speed centrifugation of the heart blood of rabbits. The histological structure of A-PRF was observed by an optical microscope. The release of growth factors in A-PRF was detected by ELISA, including platelet-derived growth factor, transforming growth factor-β, insulin-like growth factor, vascular endothelial growth factor, epidermal growth factor and fibroblast growth factor. A-PRF's cytotoxicity and capability for promoting the proliferation of rabbit BMSCs were detected by live/dead double staining and MTT methods. The effect of A-PRF on the gene expression of type Ⅱ collagen, aggrecan, alkaline phosphatase (ALP) and osteocalcin (OCN) in rabbit BMSCs was detected by real-time fluorescence quantitative polymerase chain reaction (qRT-PCR). Transwell chambers were used to determine the effect of A-PRF on the migration ability of rabbit BMSCs and the chondrocytes. Rabbit knee osteochondral defect models were established, and 18 rabbits were randomly divided into 3 groups. The A-PRF group (n=6) was implanted with A-PRF in the defect, the A-PRF+BMSCs group (n=6) was implanted with rabbit BMSCs on A-PRF, and the control group (n=6) did not undergo implantation. The rabbits were sacrificed 12 weeks after surgery and the knee joint specimens were stained with hematoxylin-eosin (H-E), toluidine blue and safranin O/fast green. Based on the surface morphology and histology of the knee joints, the International Cartilage Repair Society (ICRS) scoring system was used for macroscopic and histological scoring. Results·A-PRF had a loose network structure and can slowly release growth factors. No cytotoxicity to rabbit BMSCs was observed after adding A-PRF, and the the capability for promoting the proliferation of rabbit BMSCs was significantly increased at 24, 48 and 72 h after adding A-PRF (all P<0.05). Chondrogenesis-related gene Ⅱ collagen and aggrecan, as well as osteogenesis-related genes ALP and OCN were significantly up-regulated (all P<0.05). After adding A-PRF, the migration abilities of rabbit BMSCs and chondrocytes were significantly enhanced (both P<0.05), and the migration ability of rabbit BMSCs was significantly higher than that of chondrocytes (P=0.025). The joint surface morphology in the rabbit knee joint defect models was observed. It can be seen that the defects in the A-PRF group and the A-PRF+BMSCs group were basically restored, while the the defects in the control group were only covered by soft tissue. In the ICRS macroscopic score, there was no statistical difference between the A-PRF group and the A-PRF+BMSCs group, but the scores of the two groups were all significantly higher than those of the control group (all P<0.05). According to the histological results, both the A-PRF group and the A-PRF+BMSCs group formed osteochondral repair, but the cartilage in the A-PRF group was more mature, while the control group formed fibrous repair. In the ICRS histological score, there was no statistical difference between the A-PRF group and the A-PRF+BMSCs group, but the scores of both the groups were significantly higher than those of the control group (both P<0.05). Conclusion·Autologous A-PRF has good biocompatibility and the capability for promoting the proliferation of BMSCs. It can promote the repair of cartilage and subchondral bone both in vitro and in vivo. [ABSTRACT FROM AUTHOR]

Purpose: Osteochondral defects have a limited capacity to heal and can evolve to an early osteoarthritis. A surgical possibility is the replacement of the affected cartilaginous area with a resurfacing device BioPoly™ RS Partial Resurfacing Knee Implant. The aim of this study was to report the clinical and survival outcomes of the BioPoly™ after a minimum follow-up of 4 years. Methods: This study included all patients who had a BioPoly™ for femoral osteochondral defects greater than 1 cm2 and at least ICRS grade 2. The main outcome was to observe the KOOS and the Tegner activity score were used to assess outcomes preoperatively and at the last follow-up. The secondary outcomes were the VAS for pain, the complications rate post-surgery and survival rate of BioPoly™ at the last FU. Results: Eighteen patients with 44.4% (8/18) of women were included with a mean age of 46.6 years (11.4), a mean body mass index (BMI) of 21.5 (kg/m2) (2.3). The mean follow-up was 6.3 years (1.3). We found a significant difference comparing pre-operative KOOS score and at last follow-up [respectively, 66.56(14.37) vs 84.17(7.656), p < 0.01]. At last follow-up, the Tegner score was different [respectively, 3.05(1.3) vs 3.6(1.3), p < 0.01]. At 5 years, the survival rate was of 94.7%. Conclusions: BioPoly™ is a real alternative for femoral osteochondral defects greater than 1 cm2 and at least ICRS grade 2. It will be interesting to compare this implant to mosaicplasty technic and/or microfracture at 5 years postoperatively regarding clinical outcomes and survival rate. Level of evidence: Therapeutic level III. Prospective cohort study. [ABSTRACT FROM AUTHOR]

Purpose: To evaluate clinical, radiographic, and magnetic resonance (MR) results of costal chondrocyte-derived pellet-type scaffold-free autologous chondrocyte implantation (CCP-ACI) in osteochondral defects (ODs) up to 10-mm depth during 5 years of follow-up. Methods: Ten patients with CCP-ACI performed in ODs with depth up to 10 mm were retrospectively analyzed. The minimum follow-up period was 5 years. The median age was 36.5 (range 20–55) years. The median size and the depth of the OD lesion were 4.25 cm2 (range 2–6) and 7.0 mm (6–9), respectively. Clinically, the International Knee Documentation Committee, Lysholm, and visual analog scale pain scores were evaluated. Radiographically, the hip‒knee‒ankle (HKA) angle and the Kellgren‒Lawrence (K‒L) grade were assessed. On MR imaging, the magnetic resonance observation of cartilage repair tissue (MOCART) 2.0 score and the defect depth were evaluated. Results: All average clinical scores improved significantly by 1, 2, and 5 years postoperatively. The average HKA angle and the proportion of K‒L grade did not change significantly within 5 years. The median total MOCART scores were 50 (range 45–65), 50 (35–90), 57.5 (40–90), and 65 (50–85) at 6 months, 1 year, 2 years, and 5 years postoperatively, respectively (p = 0.001), with significant improvement at 2 years compared to that at 6 months postoperatively. The signal intensity of the repair tissue and subchondral change significantly improved from 10 (range 10–10) to 12.5 (10–15) (p = 0.036), and from 10 (10–10) to 17.5 (0–20) (p = 0.017), respectively. Significant improvements were seen at 5 years postoperatively for the former and at 2 years postoperatively for the latter. The average depths on MR imaging were 6.7, 6.7, 6.8, 6.6, and 6.6 mm preoperatively and at 6 months, 1 year, 2 years, and 5 years postoperatively with no significant changes (n.s). Conclusion: CCP-ACI provided acceptable mid-term outcomes in ODs up to 10-mm in depth without bone grafting despite of no scaffold. The procedure can be one of minimally invasive treatment options for ODs without scaffold-related problems. Level of evidence: IV. [ABSTRACT FROM AUTHOR]

Purpose: To investigate the current preferences regarding the work-up and treatment choices of juvenile osteochondritis dissecans (JOCD) of the knee, ankle and elbow among orthopaedic surgeons. Methods: An international survey was set up for all European Society of Sports Traumatology, Knee Surgery and Arthroscopy (ESSKA) members, which assessed various questions on diagnosis and treatment of JOCD of different joints. Respondents answered questions for one or more joints, based on their expertise. Proportions of answers were calculated and compared between joints. Consensus was defined as more than 75% agreement on an item; disagreement was defined as less than 25% agreement. Results: Fifty physicians responded to the survey, of whom forty-two filled out the questions on the knee, fourteen on the ankle and nine on the elbow. Plain radiography and MRI were the most used imaging modalities for the assessment and follow-up of JOCD in the knee and ankle, but not for the elbow. MRI was also the preferred method to assess the stability of a lesion in the knee and ankle. There was universal agreement on activity and/or sports restriction as the non-operative treatment of choice for JOCD. Size, stability and physeal closure were the most important prognostic factors in determining the operative technique for the elbow. For the knee, these factors were size and stability and for the ankle, these were size and location. Conclusion: Activity and/or sports restriction was the non-operative treatment of choice. Furthermore, plain radiography and MRI were the preferred imaging modalities for the knee and ankle, but not for the elbow. For determining the operative technique, physicians agreed that the size of the lesion is an important prognostic factor in all joints. These findings help us understand how juvenile osteochondritis dissecans is treated in current practice and may provide opportunities for improvement. Level of evidence: Level V. [ABSTRACT FROM AUTHOR]

Long-term outcomes of osteochondral allograft (OCA) transplantation to the humeral head have been sparsely reported in the literature. To evaluate outcomes and survivorship of OCA transplantation to the humeral head in patients with osteochondral defects at a minimum of 10 years of follow-up. A registry of patients who underwent humeral head OCA transplantation between 2004 and 2012 was reviewed. Patients completed pre and postoperative surveys including the American Shoulder and Elbow Surgeons score, Simple Shoulder Test, Short Form 12 (SF-12), and the visual analog scale. Failure was defined by conversion to shoulder arthroplasty. Fifteen of 21 (71%) patients with a minimum of ten year of follow-up (mean: 14.2 ± 2.40) were identified. Mean patient age was 26.1 ± 8.8 years at the time of transplantation and eight (53%) patients were male. Surgery was performed on the dominant shoulder in 11 of the 15 (73%) cases. The use of local anesthetic delivered via an intra-articular pain pump was the most often reported underlying etiology of chondral injury (n = 9; 60%). Eight (53%) patients were treated with an allograft plug, while seven (47%) patients were treated with a mushroom cap allograft. At final follow-up, mean American Shoulder and Elbow Surgeons (49.9 to 81.1; P =.048) and Simple Shoulder Test (43.1 to 83.3; P =.010) significantly improved compared to baseline. Changes in mean SF-12 physical (41.4 to 48.1; P =.354), SF-12 mental (57.5 to 51.8; P =.354), and visual analog scale (4.0 to 2.8; P =.618) did not reach statistical significance. Eight (53%) patients required conversion to shoulder arthroplasty at an average of 4.8 ± 4.7 years (range: 0.6-13.2). Kaplan-Meier graft survival probabilities were 60% at 10 years and 41% at 15 years. OCA transplantation to the humeral head can result in acceptable long-term function for patients with osteochondral defects. While patient-reported outcomes metrics were generally improved compared to baseline, OCA graft survival probabilities diminished with time. The findings from this study can be used to counsel future patients with significant glenohumeral cartilage injuries and set expectations about the potential for further surgery. [ABSTRACT FROM AUTHOR]

Abstract 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.

Introduction: The shift from manual to machine-based operations has also affected the creation of cartilage defect models. Manual drilling lacks precision and consistency compared to power drills, which offer controlled speed and depth. Moreover, manual burrs may produce defects with irregular edges and uneven surfaces. We introduce a superior method utilizing a power drill with a brad point bit to overcome these limitations, ensuring precision, consistency, and ergonomics. Methods: Our innovative approach uses a brad point drill bit to generate cartilage repair animal models. Tissue sections on day 90 were stained using Hematoxylin and Eosin, Safranin-O, and Masson's trichrome to assess proteoglycan and collagen contents. In contrast, differentiation of hyaline cartilage was evaluated using RGB trichrome staining. Results: This technique can be considered refined compared to conventional methods. The spur-cutting edges bring down splintering, resulting in a smooth, clean defect. The wide flute in the drill bit helps in the smooth and continuous outflow of debris without plugging into the defect. The histological and radiographic findings demonstrated the suitability of these models for proficiently creating and assessing cartilage regeneration over 90 days. Conclusion: Although preliminary findings are promising, further studies will be helpful to standardize and establish this technique. This proof of concept paper provides a foundation for future studies that aim to compare the animal model with other existing models, emphasizing the need for further investigation.

Osteochondral regeneration remains a great challenge due to the limited self‐healing ability and the complexity of its hierarchical structure and composition. Mg2+ and hypoxia are two effective modulators in boosting chondrogenesis. To this end, a double‐layered scaffold (D) consisting of a hydrogel layer on a porous cryogel is fabricated to mimic the hierarchical structure of osteochondral tissue. An Mg2+ gradient is incorporated into the double‐layered scaffold with hypoxia‐mimicking deferoxamine (DFO) embedded in the hydrogel (D‐Mg‐DFO), which remarkably augments the dual‐lineage regeneration of both cartilage and subchondral bone. The higher Mg2+ supplementation from the upper hydrogel, associated with its hypoxia‐mimicking situation and small pore size, exhibits promotive effects on chondrogenic differentiation. The lower Mg2+ supplementation from the bottom cryogel, associated with its interconnected macroporous structure, achieves multiple contributions in stem cell migration from bone marrow cavity, matrix mineralization, and osteogenesis. Furthermore, rabbits' trochlea osteochondral defects are established to evaluate the regenerative outcome. Compared to control scaffolds containing only Mg2+ or DFO, the D‐Mg‐DFO scaffold presents the best regenerative effect under the synergistic contribution of multiple factors. Overall, this work provides a new design of scaffold toward an effective repair of cartilage defect. [ABSTRACT FROM AUTHOR]

Osteochondral defects pose a great challenge and a satisfactory strategy for their repair has yet to be identified. In particular, poor repair could result in the generation of fibrous cartilage and subchondral bone, causing the degeneration of osteochondral tissue and eventually leading to repair failure. Herein, taking inspiration from the chemical elements inherent in the natural extracellular matrix (ECM), we proposed a novel ECM-mimicking scaffold composed of natural polysaccharides and polypeptides for osteochondral repair. By meticulously modifying natural biopolymers to form reversible guest–host and rigid covalent networks, the scaffold not only exhibited outstanding biocompatibility, cell adaptability, and biodegradability, but also had excellent mechanical properties that can cater to the environment of osteochondral tissue. Additionally, benefiting from the drug-loading group, chondrogenic and osteogenic drugs could be precisely integrated into the specific zone of the scaffold, providing a tissue-specific microenvironment to facilitate bone and cartilage differentiation. In rabbit osteochondral defects, the ECM-inspired scaffold not only showed a strong capacity to promote hyaline cartilage formation with typical lacuna structure, sufficient mechanical strength, good elasticity, and cartilage-specific ECM deposition, but also accelerated the regeneration of quality subchondral bone with high bone mineralization density. Furthermore, the new cartilage and subchondral bone were heterogeneous, a trait that is typical of the natural landscape, reflecting the gradual progression from cartilage to subchondral bone. These results suggest the potential value of this bioinspired osteochondral scaffold for clinical applications. [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]

Purpose: Chondral injuries secondary to traumatic patella dislocation are common, and a subgroup of these are significant defects with fragments amenable to fixation. There is a paucity of published evidence assessing patients managed with combined acute patellofemoral stabilisation and osteochondral fixation. The purpose of this study is to report the outcomes of patients with osteochondral injuries secondary to acute traumatic patella dislocation treated with combined early fragment fixation and MPFL reconstruction using a quadriceps tendon turndown technique which has distinct advantages for this cohort, including preventing chondral overloading and non-violation of the patella bone. Methods: Patients who underwent combined quadriceps tendon MPFL reconstruction and osteochondral fixation were included. Patient demographics, defect characteristics, complications and reoperations were evaluated. Patients were assessed with Lysholm, Kujala, KOOS-PF scores and satisfaction scale at follow up. Pre-operative MRI was assessed for presence of radiological risk factors for patella dislocation and post-operative MRI was used to assess cartilage quality with MOCART 2.0 score. Results: A total of 19 patients (63.2% female) were included. The mean age was 17.4 ± 4.8 years and patients were followed up at a mean 15.8 ± 5.1 months post-surgery. The mean defect size was 2.4 cm2 ± 1.3 cm2, with the most common defect location being the patella (13/19; 68.4%) followed by the lateral femoral condyle (5/19; 26.3%). At final follow up, the overall mean Lysholm, Kujala, and KOOS-PF scores were 84.9 ± 11.1, 89.7 ± 5.8 and 80.6 ± 13.6, respectively. Seventeen patients (89.5%) were satisfied with their outcome. The mean MOCART 2.0 score at final follow-up was 72.5. One patient required medial capsular plication with removal of a loose chondral body and microfracture and 3 knees required minor reoperations. Conclusion: Combined acute osteochondral fragment fixation and MPFL reconstruction using a quadriceps tendon graft offers good radiological and patient-reported outcomes with high satisfaction and low rates of recurrent patella dislocation. To our knowledge, this is currently the largest series of its kind in the literature and the results of this study provide a rationale for a combined approach using a quadriceps tendon graft for this cohort. Level of evidence: Level IV. [ABSTRACT FROM AUTHOR]

The treatment of cartilage defects in trauma injuries and degenerative diseases represents a challenge for orthopedists. Advanced mesenchymal stromal cell (MSC)-based therapies are currently of interest for the repair of damaged cartilage. However, an approved system for MSC delivery and maintenance in the defect is still missing. This study aimed to evaluate the effect of autologous porcine bone marrow MSCs anchored in a commercially available polyglycolic acid-hyaluronan scaffold (Chondrotissue®) using autologous blood plasma-based hydrogel in the repair of osteochondral defects in a large animal model. The osteochondral defects were induced in twenty-four minipigs with terminated skeletal growth. Eight animals were left untreated, eight were treated with Chondrotissue® and eight received Chondrotissue® loaded with MSCs. The animals were terminated 90 days after surgery. Macroscopically, the untreated defects were filled with newly formed tissue to a greater extent than in the other groups. The histological evaluations showed that the defects treated with Chondrotissue® and Chondrotissue® loaded with pBMSCs contained a higher amount of hyaline cartilage and a lower amount of connective tissue, while untreated defects contained a higher amount of connective tissue and a lower amount of hyaline cartilage. In addition, undifferentiated connective tissue was observed at the edges of defects receiving Chondrotissue® loaded with MSCs, which may indicate the extracellular matrix production by transplanted MSCs. The immunological analysis of the blood samples revealed no immune response activation by MSCs application. This study demonstrated the successful and safe immobilization of MSCs in commercially available scaffolds and defect sites for cartilage defect repair. [ABSTRACT FROM AUTHOR]

BackgroundThe repair of osteochondral lesions remains a challenge due to its poor vascularity and limited healing potential. Micronized cartilage matrix (MCM) is dehydrated, decellularized, micronized allogeneic cartilage matrix that contains the components of native articular tissue and is hypothesized to serve as a scaffold for the formation of hyaline-like tissue. Our objective was to demonstrate in vitro that the use of MCM combined with mesenchymal stem cells (MSCs) can lead to the formation of hyaline-like cartilage tissue in a single-stage treatment model.DesignIn group 1 (no wash), 250 µL MCM was reconstituted in 150 µL Dulbecco's phosphate-buffered saline (DPBS) for 5 minutes. Group 2 (saline wash) included 250 µL MCM washed in 20 mL DPBS for 30 minutes, then aspirated to remove all DPBS and reconstituted in 150 µL DPBS. Group 3 (serum wash): 250µL MCM washed in 20 mL DPBS for 30 minutes, then aspirated and reconstituted in 150 µL fetal bovine serum. Each group was then added to 50 µL solution of MSC suspended in DPBS at a concentration of 1.2 × 106 cells/350 µL. After 3 weeks, the defects were extracted and sectioned to perform viability and histologic analyses.ResultsStem cells without rehydration of the MCM showed almost no viability whereas near complete cell viability was seen after rehydration with serum or saline solution, ultimately leading to chondrogenic differentiation and adhesion to the MCM particles.ConclusionWe have shown in this proof-of-concept in vitro study that MCM can serve as a scaffold for the growth of cartilage tissue for the treatment of osteochondral lesions.

The development of surface modification techniques has brought about a major paradigm shift in the clinical applications of bone tissue regeneration. Biofabrication strategies enable the creation of scaffolds with specific microstructural environments and biological components. Lithium (Li) has been reported to exhibit anti-inflammatory, osteogenic, and chondrogenic properties by promoting several intracellular signaling pathways. Currently, research focuses on fabricating scaffolds with simultaneous dual bioactivities to enhance osteochondral regeneration. In this study, we modified the surface of calcium silicate (CS) scaffolds with Li using a simple immersion technique and evaluated their capabilities for bone regeneration. The results showed that Li ions could be easily coated onto the surfaces of CS scaffolds without affecting the microstructural properties of CS itself. Furthermore, the modifications did not affect the printing capabilities of the CS, and porous scaffolds could be fabricated via extrusion. Moreover, the presence of Li improved the surface roughness and hydrophilicity, thus leading to enhanced secretion of osteochondral-related regeneration factors, such as alkaline phosphatase (ALP), bone sialoprotein (BSP), and collagen II (Col II) proteins. Subsequent in vivo studies, including histological and micro-CT analyses, confirmed that the Li-modified CS scaffolds promoted osteochondral regeneration. The transcriptome analysis suggested that the enhanced osteochondrogenic capabilities of our scaffolds were influenced by paracrine exosomes. We hope this study will inspire further research on osteochondral regeneration.

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]