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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: 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]

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

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.

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.

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: 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.

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.

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.

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

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.

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.

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]

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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.

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.

INTRODUCTION:Delamination of the chondral surface of an osteochondral allograft (OCA) from the underlying cancellous bone has been described as a mode of failure after implantation in the knee. Our hypothesis was that increased storage time of the OCA is associated with increased risk of graft delamination after implantation. METHODS:Prospective data on 13 patients with evidence of OCA delamination identified on magnetic resonance imaging or during subsequent surgery from 2000 to 2015 were reviewed. A cohort of 33 patients without evidence of graft delamination were then matched to the delamination group based on recipient age, sex, body mass index (BMI), and chondral defect location. The matched cohort size was established based on a power calculation for determining differences in OCA storage times. All patients had a minimum 2-year follow-up. RESULTS:There was no difference in donor age, donor sex, and graft storage time between groups (30 vs. 31 days, P = 0.78). There were no differences between number of previous ipsilateral knee surgeries (1.8 vs. 0.84, P = 0.26), BMI (26.8 vs. 25.0 kg/m2, P = 0.31), total chondral defect size (6.5 vs. 5.8 cm2, P = 0.41) or preoperative Marx activity scores between groups. CONCLUSION:There is no association between OCA storage time, activity level scores, or number of previous ipsilateral knee surgeries and graft delamination in our patient population. Further work is needed to identify the etiology for this mode of failure of OCAs.

Osteochondral (OC) defects cannot adequately repair themselves due to their sophisticated layered structure and lack of blood supply in cartilage. Although therapeutic interventions are reaching an advanced stage, current clinical therapies to repair defects are in their infancy. Among the possible therapies, OC tissue engineering has shown considerable promise, and multiple approaches utilizing scaffolds, cells, and bioactive factors have been pursued. The most recent trend in OC tissue engineering has been to design gradient scaffolds using different materials and construction strategies (such as bi-layered, multi-layered, and continuous gradient structures) to mimic the physiological and mechanical properties of OC tissues while further enabling OC repair. This review focuses specifically on design and construction strategies for gradient scaffolds and their role in the successful engineering of OC tissues. The current dilemmas in the field of OC defect repair and the efforts of tissue engineering to address these challenges were reviewed. In addition, the advantages and limitations of the typical fabrication techniques for gradient scaffolds were discussed, with examples of recent studies summarizing the future prospects for integrated gradient scaffold construction. This updated and enlightening review could provide insights into our current understanding of gradient scaffolds in OC tissue engineering. [ABSTRACT FROM AUTHOR]

Abstract 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.

BackgroundFirst-time patellar dislocation with an associated chondral or osteochondral loose body is typically treated operatively to address the loose fragment. The incidence of recurrent instability in this patient population if the medial patellofemoral ligament (MPFL) is not reconstructed is unknown.PurposeTo determine the recurrent instability rate in patients undergoing surgery for patellar instability with chondral or osteochondral loose bodies, as well as to identify and stratify risk factors for recurrent instability.Study designCase series; Level of evidence, 4.MethodsThis was a retrospective analysis of adolescent patients treated operatively for acute patellar dislocation with associated chondral or osteochondral loose bodies between 2010 and 2016 at a single pediatric level I trauma center with minimum 2-year follow-up. Potential demographic, injury-related, radiographic, and surgical risk factors were recorded. The primary outcome variable was recurrent subluxation and/or dislocation. Secondary outcome variables included need for additional procedures, Kujala score, Single Assessment Numerical Evaluation (SANE) score, and patient satisfaction.ResultsForty-one patients were included. In total, 61% experienced recurrent instability at a mean follow-up of 4.1 years and 39% required subsequent MPFL reconstruction. Tibial tubercle-trochlear groove (TT-TG) distance greater than 15 mm was a risk factor for recurrent instability ( P = .03). Patients with TT-TG distance greater than 15 mm and greater than 20 mm had recurrent instability rates of 75% and 86%, respectively. MPFL repair did not reduce the rate of recurrent instability ( P = .87). Recurrent instability was associated with significantly worse mean Kujala (93.9 vs 83.0; P = .01), SANE (88.9 vs 73.1; P = .01), and patient satisfaction scores (9.4 vs 7.3; P = .002).ConclusionIf the MPFL is not reconstructed during index loose body treatment, children have a 61% recurrent instability rate. Patients with TT-TG distance greater than 15 mm, and particularly greater than 20 mm, are at highest risk for recurrent instability.

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]

The regeneration of cartilage and osteochondral defects remains one of the most challenging clinical problems in orthopedic surgery. Currently, tissue-engineering techniques based on the delivery of appropriate growth factors and mesenchymal stem cells (MSCs) in hydrogel scaffolds are considered as the most promising therapeutic strategy for osteochondral defects regeneration. In this study, we fabricated a heparin-conjugated fibrin (HCF) hydrogel with synovium-derived mesenchymal stem cells (SDMSCs), transforming growth factor-β1 (TGF-β1) and bone morphogenetic protein-4 (BMP-4) to repair osteochondral defects in a rabbit model. An in vitro study showed that HCF hydrogel exhibited good biocompatibility, a slow degradation rate and sustained release of TGF-β1 and BMP-4 over 4 weeks. Macroscopic and histological evaluations revealed that implantation of HCF hydrogel with SDMSCs, TGF-β1 and BMP-4 significantly enhanced the regeneration of hyaline cartilage and the subchondral bone plate in osteochondral defects within 12 weeks compared to hydrogels with SDMSCs or growth factors alone. Thus, these data suggest that combined delivery of SDMSCs with TGF-β1 and BMP-4 in HCF hydrogel may synergistically enhance the therapeutic efficacy of osteochondral defect repair of the knee joints. [ABSTRACT FROM AUTHOR]

With the increase in population aging, the tendency of osteochondral injury will be accelerated, and repairing materials are increasingly needed for the optimization of the regenerative processes in bone and cartilage recovery. The local environment of the injury sites and the deficiency of Mg2+ retards the repairing period via inhibiting the progenitor osteogenesis and chondrogenesis cells' recruitment, proliferation, and differentiation, which results in the sluggish progress in the osteochondral repairing materials design. In this article, we elucidate the Mg2+-concentration specified effect on the cell proliferation, osteochondral gene expression, and differentiation of modeling chondrocytes (extracted from New Zealand white rabbit) and osteoblasts (MC3T3-E1). The concentration of Mg2+ in the culture medium affects the proliferation, chondrogenesis, and osteogenesis: (i) Appropriate concentrations of Mg2+ promote the proliferation of chondrocytes (1.25–10.0 mM) and MC3T3-E1 cells (2.5–30.0 mM); (ii) the optimal concentration of Mg2+ that promotes the gene expression of noncalcified cartilage is 15 mM, calcified cartilage 10 mM, and subchondral bone 5 mM, respectively; (iii) overdosed Mg2+ leads to the inhibition of cell activity for either chondrocytes (>20 mM) or osteoblasts (>30 mM). The biomimetic elucidation for orchestrating the allocation of gradient concentration of Mg2+ in accordance of the physiological condition is crucial for designing the accurate microenvironment in osteochondral injury defects for optimization of bone and cartilage repairing materials in the future. [ABSTRACT FROM AUTHOR]

Background: Some surgeons are now considering fixation of traumatic chondral-only fragments in juvenile knees, but few data remain to guide treatment. Purpose: To determine if surgical fixation of chondral-only fragments in the juvenile knee results in an adequate healing response with successful imaging and clinical outcomes. Study Design: Case series; Level of evidence, 4. Methods: Data were collected on 16 skeletally immature patients treated with fixation of chondral-only fragments with a minimum 1-year follow-up. Patients were selected by the operating surgeons based on the quality and size of the chondral fragment. Demographic data, lesion characteristics, surgical procedure details, complications, and postoperative imaging were assessed. Validated outcome measures were collected pre- and postoperatively and included the following scores: International Knee Documentation Committee (IKDC), Marx Activity Scale, Knee injury and Osteoarthritis Outcome Score (KOOS), Hospital for Special Surgery Pediatric Functional Activity–Brief Scale (HSS Pedi-FABS), Patient-Reported Outcomes Measurement Information System (PROMIS)–Physical Health and PROMIS–Psychological Health, and Tegner. Results: The mean age of our patient cohort was 14.9 years. The mean size of the repaired defects measured 3.2 cm2. Injury sites included the patella (n = 1), medial femoral condyle (n = 3), trochlea (n = 4), and lateral femoral condyle (n = 8). Within the mean follow-up time of 42.3 months (range, 15-145), there was 1 clinical failure with loosening of the chondral fragment and the need for reoperation. At a mean follow-up of 3.5 years, the mean (interquartile range) patient-reported outcome scores were as follows: IKDC, 95.2 (94.3-100); Marx Activity Scale, 11.5 (11.5-16); KOOS, 95.81 (93.5-95.81); HSS Pedi-FABS, 16.94 (11.5-26); PROMIS–Physical Health, 93.75% (90%-100%); PROMIS–Psychological Health, 90% (88.75%-100%); and Tegner, 5.69 (4.75-7). All patients who were engaged in sports before injury returned to the same or higher level of competition with the exception of 1 patient. Conclusion: Primary repair of chondral-only injuries with internal fixation can be a successful treatment option in selected patients. Clinical and imaging results at final follow-up suggest that reintegration of the cartilage fragment is achievable and leads to excellent clinical function and a high return-to-sports rate. [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]

Introduction: Distal femoral cartilage lesions can be treated using osteochondral autograft transfer (OAT). When impacting plugs into a recipient site, the cartilage may fracture. This study aimed to analyze OAT donor regions and impaction energies to identify characteristics that lead to fracture., Methods: Fifteen cadaver femurs were used with OAT plugs harvested from the following regions: lateral and medial trochlea (LT and MT), lateral and medial intercondylar notch (LIN and MIN). Plugs were impacted into a bone surrogate block using a custom anvil-type system with pre-determined impact heights; 30, 50, 70, and 90 mm. Each plug's cartilage was examined and determined to be intact or fractured. Chi-square was used to compare the rate of chondral fracture for each region., Results: In all, 221 plugs were included. The overall rate of chondral fracture was 45.7%. There was a significant difference in the rate of fracture between regions, with LIN, MIN, LT, and MT, having a fracture rate of 46.6%, 62.7%, 25.0%, and 51.9%, respectively ( P = 0.001). An impact height of 30 mm resulted in a fracture rate of 17.7%. Increasing the impact height from 30 to 50 mm resulted in significantly increased chondral fracture risk ( P = 0.001)., Conclusion: Different donor regions have varying rates of chondral fracture during OAT plug impaction, with the lateral and medial trochlea being the most resistant to chondral fracture at lower forces. Increased impact energy increases risk of chondral fracture. Surgeons should maintain caution and utilize lower impact energy when inserting OAT plugs., Competing Interests: Declaration of Conflicting InterestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Osteochondral defects involving cartilage and subchondral bone are difficult to repair. Recently, scientists have attempted to develop composite scaffolds for repair of osteochondral injuries. However, the available composite scaffolds do not fully recapitulate the functions of the cartilage, subchondral bone, and cancellous bone. In this study, we developed a bioactive multiphase scaffold by decellularizing an intact osteochondral graft for osteochondral repair. The porosity and mechanical properties of the scaffolds were optimized using laser drilling and collagen digestion. The scaffold promoted the recellularization of the cartilage layer. The experimental results showed that the multiphasic scaffolds had excellent mechanical properties and structural stability similar to that of the normal rabbit osteochondral tissue. The in vitro analysis showed that the scaffold promoted zone-specific gene expression. Approximately 12 weeks after in vivo implantation, the multiphasic scaffold significantly facilitated the concurrent regeneration of cartilage and subchondral bone in a rabbit model (detected using gross and micro-computed tomography images, histological staining, immunohistochemistry, and visualization of the collagen network). Overall, this study provides ideas for the development of new multiphasic scaffolds for osteochondral defect repair.

Osteochondral repair remains a challenge in clinical practice nowadays despite extensive advances in tissue engineering. The insufficient recruitment of endogenous cells in the early stage and incomplete cell differentiation in the later stage constitute the major difficulty of osteochondral repair. Here, a novel all-silk-derived multifunctional biomaterial platform for osteochondral engineering is reported. The bilayer methacrylated silk fibroin (SilMA) hydrogel was fabricated through stratified photocuring as the basic provisional matrix for tissue regeneration. Platelet-rich plasma (PRP) incorporation promoted the migration and pre-differentiation of the bone marrow mesenchymal stem cells (BMSCs) in the early stage of implantation. The long-term regulation of BMSCs chondrogenesis and osteogenesis was realized by the stratified anchoring of the silk fibroin (SF) microspheres respectively loaded with Kartogenin (KGN) and berberine (BBR) in the hydrogel. The composite hydrogels were further demonstrated to promote BMSCs chondrogenic and osteogenic differentiation under an inflammatory microenvironment and to achieve satisfying cartilage and subchondral bone regeneration with great biocompatibility after 8 weeks of implantation. Since all the components used are readily available and biocompatible and can be efficiently integrated via a simple process, this composite hydrogel scaffold has tremendous potential for clinical use in osteochondral regeneration.

Subchondral bone marrow lesions (BMLs) are areas of disease within subchondral bone that appear as T1 hypointense and T2 hyperintense ill-defined areas of bone marrow on magnetic resonance imaging. The most common bone marrow lesions include subchondral lesions related to osteoarthritis, osteochondral defects, and avascular necrosis. Emerging therapies include autologous biologic therapeutics, in particular mesenchymal stem cells (MSCs), to maintain and improve cartilage health; MSCs have become a potential treatment option for BMLs given the unmet need for disease modification. Active areas in the preclinical research of bone marrow lesions include the paracrine function of MSCs in pathways of angiogenesis and inflammation, and the use of bioactive scaffolds to optimize the environment for implanted MSCs by facilitating chondrogenesis and higher bone volumes. A review of the clinical data demonstrates improvements in pain and functional outcomes when patients with knee osteoarthritis were treated with MSCs, suggesting that BM-MSCs can be a safe and effective treatment for patients with painful knee osteoarthritis with or without bone marrow lesions. Preliminary data examining MSCs in osteochondral defects suggest they can be beneficial as a subchondral injection alone, or as a surgical augmentation. In patients with hip avascular necrosis, those with earlier stage disease have improved outcomes when core decompression is augmented with MSCs, whereas patients in later stages post-collapse have equivalent outcomes with or without MSC treatment. While the evidence for the use of MSCs in conditions with associated bone marrow lesions seems promising, there remains a need for continued investigation into this treatment as a viable treatment option.

Osteochondral structure reconstruction by tissue engineering, a challenge in regenerative medicine, requires a scaffold that ensures both articular cartilage and subchondral bone remodeling. Functional hydrogels and scaffolds present a strategy for the controlled delivery of signaling molecules (growth factors and therapeutic drugs) and are considered a promising therapeutic approach. Icariin is a pharmacologically-active small molecule of prenylated flavonol glycoside and the main bioactive flavonoid isolated from Epimedium spp. The in vitro and in vivo testing of icariin showed chondrogenic and ostseoinductive effects, comparable to bone morphogenetic proteins, and suggested its use as an alternative to growth factors, representing a low-cost, promising approach for osteochondral regeneration. This paper reviews the complex structure of the osteochondral tissue, underlining the main aspects of osteochondral defects and those specifically occurring in osteoarthritis. The significance of icariin's structure and the extraction methods were emphasized. Studies revealing the valuable chondrogenic and osteogenic effects of icariin for osteochondral restoration were also reviewed. The review highlighted th recent state-of-the-art related to hydrogels and scaffolds enriched with icariin developed as biocompatible materials for osteochondral regeneration strategies. [ABSTRACT FROM AUTHOR]

Background. The relevance of the talar dome osteochondral lesions problem is assosiated with the difficulties of diagnosis, the lack of unified treatment algorythm and the great number of unsatisfactory clinical and functional results. In the last decade, there has been increasing interest in this topic in the literature, which is demonstrated by a great number of publications with series of observations or clinical cases. However, attempts to create the universal algorithm for this group of patients treatment are limited by the low level of existing studies evidence, high frequency of the new data publications, as well as the impossibility of using a number of surgical methods in different countries for legislative or other reasons. The aim is to determine the current state of the problem of the talar dome osteochondral lesions surgical treatment and to identify types of surgical interventions in patients with the studied pathology. Material and methods. 120 international articles published from 2000 to 2021, as well as 18 domestic publications for the period from 2007 to 2021 were selected for the literature analysis. The search for publications was carried out in the PubMed/MedLine and eLibrary databases. Results. The most widespread are surgical interventions aimed at stimulation of the bone marrow, and plastic surgery using osteochondral auto - and allografts. Currently, there is no consensus on the indications for different types of surgical methods, and the previously used indications are being questioned. This determines the need to improve diagnostic and treatment concepts. Conclusion. The studied literature cannot fully answer a number of questions related to the methods of surgical treatment of patients with symptomatic osteochondral lesions of the talar dome and indications for them. A more detailed assessment of the medium- and long-term clinical outcomes of various surgical methods and the development of algorithms for this group of patients treatment, specific for different countries, are needed.

Abstract 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

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]

There is an unmet need for novel and efficacious therapeutics for regenerating injured articular cartilage in progressive osteoarthritis (OA) and/or trauma. Mesenchymal stem cells (MSCs) are particularly promising for their chondrogenic differentiation, local healing environment modulation, and tissue- and organism-specific activity; however, despite early in vivo success, MSCs require further investigation in highly-translatable models prior to disseminated clinical usage. Large animal models, such as canine, porcine, ruminant, and equine models, are particularly valuable for studying allogenic and xenogenic human MSCs in a human-like osteochondral microenvironment, and thus play a critical role in identifying promising approaches for subsequent clinical investigation. In this mini-review, we focus on [1] considerations for MSC-harnessing studies in each large animal model, [2] source tissues and organisms of MSCs for large animal studies, and [3] tissue engineering strategies for optimizing MSC-based cartilage regeneration in large animal models, with a focus on research published within the last 5 years. We also highlight the dearth of standard assessments and protocols regarding several crucial aspects of MSC-harnessing cartilage regeneration in large animal models, and call for further research to maximize the translatability of future MSC findings.

• 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]

The osteochondral (OC) unit plays a pivotal role in joint lubrication and in the transmission of constraints to bones during movement. The OC unit does not spontaneously heal; therefore, OC defects are considered to be one of the major risk factors for developing long‐term degenerative joint diseases such as osteoarthritis. Yet, there is currently no curative treatment for OC defects, and OC regeneration remains an unmet medical challenge. In this context, a plethora of tissue engineering strategies have been envisioned over the last two decades, such as combining cells, biological molecules, and/or biomaterials, yet with little evidence of successful clinical transfer to date. This striking observation must be put into perspective with the difficulty in comparing studies to identify overall key elements for success. This systematic review aims to provide a deeper insight into the field of material‐assisted strategies for OC regeneration, with particular considerations for the therapeutic potential of the different approaches (with or without cells or biological molecules), and current OC regeneration evaluation methods. After a brief description of the biological complexity of the OC unit, the recent literature is thoroughly analyzed, and the major pitfalls, emerging key elements, and new paths to success are identified and discussed. [ABSTRACT FROM AUTHOR]