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Exogenous dual delivery of progenitor cell population and therapeutic growth factors (GFs) is one of alternative tissue engineering strategies for osteochondral tissue regeneration. In the present study, an implantable dual delivery platform was developed using coacervates (Coa) (i.e., a tertiary complex of poly(ethylene argininylaspartate diglyceride) (PEAD) polycation, heparin, and cargo insulin-like growth factor-1 (IGF-1), in thiolated gelatin (gelatin-SH)/ poly(ethylene glycol) diacrylate (PEGDA) interpenetrating network (IPN) hydrogels. Since Coa is able to protect cargo GF and maintain its long-term bioactivity, it is speculated that Coa-mediated delivery of chondrogenic factor IGF-1 with the aid of adipose-derived stem cells (ADSCs) would synergistically facilitate osteochondral tissue repair during physiological regeneration process. Our results indicate that gelatin-SH/PEGDA IPN hydrogels demonstrated biocompatibility and mechanical properties for a possible long-term transplantation, and PEAD-base Coa exhibited a sustained release of bioactive IGF-1 over 3 weeks. Subsequently, released IGF-1 from Coa could effectively induce chondrogenic differentiation of embedded ADSCs in the hydrogel, by showing enhanced glycosaminoglycan deposition and expression of chondrogenesis-associated genes. More importantly, at 12 weeks post-implantation in a rabbit full thickness osteochondral defect model, the quality of regenerative tissues in both chondral and subchondral layers was significantly improved in dual delivery of ADSC and IGF-1 in Coa encapsulated in gelatin-SH/PEGDA IPN hydrogels, as compared with a single delivery of ADSC only and a dual delivery without Coa. Therefore, we conclude that our Coa-embedded composite hydrogel platform could effectively augment osteochondral tissue regeneration holds promise for a feasible osteoarthritis therapeutic application., (Copyright © 2020. Published by Elsevier B.V.)

Background: Chondrogenic mesenchymal stem cells (MSCs) have not yet been used to address the clinical demands of large osteochondral joint surface defects. In this study, self-assembling tissue intermediates (TIs) derived from human periosteum-derived stem/progenitor cells (hPDCs) were generated and validated for stable cartilage formation in vivo using two different animal models., Methods: hPDCs were aggregated and cultured in the presence of a novel growth factor (GF) cocktail comprising of transforming growth factor (TGF)-β1, bone morphogenetic protein (BMP)2, growth differentiation factor (GDF)5, BMP6, and fibroblast growth factor (FGF)2. Quantitative polymerase chain reaction (PCR) and immunohistochemistry were used to study in vitro differentiation. Aggregates were then implanted ectopically in nude mice and orthotopically in critical-size osteochondral defects in nude rats and evaluated by microcomputed tomography (µCT) and immunohistochemistry., Results: Gene expression analysis after 28 days of in vitro culture revealed the expression of early and late chondrogenic markers and a significant upregulation of NOGGIN as compared to human articular chondrocytes (hACs). Histological examination revealed a bilayered structure comprising of chondrocytes at different stages of maturity. Ectopically, TIs generated both bone and mineralized cartilage at 8 weeks after implantation. Osteochondral defects treated with TIs displayed glycosaminoglycan (GAG) production, type-II collagen, and lubricin expression. Immunostaining for human nuclei protein suggested that hPDCs contributed to both subchondral bone and articular cartilage repair., Conclusion: Our data indicate that in vitro derived osteochondral-like tissues can be generated from hPDCs, which are capable of producing bone and cartilage ectopically and behave orthotopically as osteochondral units.

Objective: To investigate the effect of decellularized cartilage-derived matrix (CDM) scaffolds, by itself and as a composite scaffold with a calcium phosphate (CaP) base, for the repair of osteochondral defects. It was hypothesized that the chondral defects would heal with fibrocartilaginous tissue and that the composite scaffold would result in better bone formation., Methods: After an 8-week pilot experiment in a single horse, scaffolds were implanted in eight healthy horses in osteochondral defects on the medial trochlear ridge of the femur. In one joint a composite CDM-CaP scaffold was implanted (+P), in the contralateral joint a CDM only (-P) scaffold. After euthanasia at 6 months, tissues were analysed by histology, immunohistochemistry, micro-CT, biochemistry and biomechanical evaluation., Results: The 8-week pilot showed encouraging formation of bone and cartilage, but incomplete defect filling. At 6 months, micro-CT and histology showed much more limited filling of the defect, but the CaP component of the +P scaffolds was well integrated with the surrounding bone. The repair tissue was fibrotic with high collagen type I and low type II content and with no differences between the groups. There were also no biochemical differences between the groups and repair tissue was much less stiff than normal tissue (P < 0.0001)., Conclusions: The implants failed to produce reasonable repair tissue in this osteochondral defect model, although the CaP base in the -P group integrated well with the recipient bone. The study stresses the importance of long-term in vivo studies to assess the efficacy of cartilage repair techniques., (Copyright © 2016 Osteoarthritis Research Society International. Published by Elsevier Ltd. All rights reserved.)

Developing successful tissue engineering strategies requires an understanding of how cells within an implanted scaffold interact with the host environment. The objective of this study was to use a computational mechanobiological model to explore how the design of a cell-laden scaffold influences the spatial formation of cartilage and bone within an osteochondral defect. Tissue differentiation was predicted using a previously developed model, in which cell fate depends on the local oxygen tension and the mechanical environment within a damaged joint. This model was first updated to include a rule through which mature cartilage was resistant to both terminal differentiation and vascularization, and then used to simulate osteochondral defect repair following the implantation of various cell-free and cell-laden scaffolds. While delivery of a cell-free scaffold led to only marginal improvements in joint repair, implantation of a cell-laden bilayered scaffold was predicted to significantly increase cartilage formation in the chondral phase of the scaffold. Despite these improvements, bone still progressed into the chondral regions of these engineered implants by means of endochondral ossification during the later stages of repair. This led to thinning of the cartilage tissue, which in turn resulted in a prediction of increased tissue strain and, eventually, increases in fibrocartilage formation as a result of this altered mechanical stimulus. In contrast to this, the model predicted that implantation of a trilayered scaffold, which included a compact layer to confine angiogenesis to the osseous phase of the defect, further improves joint regeneration. This is achieved by allowing chondrogenically primed mesenchymal stem cells, which are seeded into the chondral phase of the implant, to form stable cartilage, which was ultimately resistant to both vascularization and endochondral ossification. These models provide a framework for exploring how environmental factors impact bone, cartilage, and joint regeneration and can be used to inform the design of new tissue engineering strategies for use in orthopedic medicine.

Background: The purpose of this study was to review the clinical results of irradiated fresh frozen osteochondral allografts for large osteochondral defects of the knee using the Mega-OATS technique., Methods: Nine patients with a mean age of 32.1±6.6 (18 to 44) underwent Mega-OATS transplantation with irradiated (2.5Mrad), fresh frozen distal femur allograft. Three patients also underwent ACL-reconstruction; one patient a high tibial osteotomy. The underlying indication was osteochondrosis dissecans in four and trauma in five patients. The defect size was 25×25mm in three patients and 30×30 in six patients and the depth ranged from eight to 14mm. All OCD lesions were located on the medial femoral condyle; two of the traumatic lesions were located on the lateral femoral condyle. Clinical outcome was assessed using the Lysholm and IKDC scores. Radiographic incorporation was evaluated using serial radiographs and MR imaging at one year post surgery. All patients were reviewed at three, six, 12, and 24months following surgery., Results: The Lysholm (IKDC) score improved significantly (p=0.02 resp. p=0.007) within and between patients during the follow-up period from 40.9 (37) to 90.9 (87.1) at 2years. Radiographic union was observed in all patients at three months; on MR imaging at one year osseous integration was observed in eight patients. Graft subsidence with loss of the overlying cartilage was observed in one and subchondral cystic changes at the implantation side were seen in another patient., Conclusion: The results of this case series suggest that irradiated osteochondral allograft provides significant medium-term clinical improvement in patients treated for large osteochondral lesions of the femoral condyles., Level of Evidence: IV, case series., (Copyright © 2016 Elsevier B.V. All rights reserved.)

Background: The treatment of patellofemoral cartilage injuries can be challenging. Osteochondral allograft (OCA) transplantation has been used as a treatment option for a range of cartilage disorders., Purpose: To evaluate functional outcomes and survivorship of the grafts among patients who underwent OCA for patellar cartilage injuries., Study Design: Case series; Level of evidence, 4., Methods: An institutional review board-approved OCA database was used to identify 27 patients (28 knees) who underwent isolated OCA transplantation of the patella between 1983 and 2010. All patients had a minimum 2-year follow-up. The mean age of the patients was 33.7 years (range, 14-64 years); 54% were female. Twenty-six (92.9%) knees had previous surgery (mean, 3.2 procedures; range, 1-10 procedures). The mean allograft area was 10.1 cm(2) (range, 4.0-18.0 cm(2)). Patients returned for clinical evaluation or were contacted via telephone for follow-up. The number and type of reoperations were assessed. Any reoperation resulting in removal of the allograft was considered a failure of the OCA transplantation. Patients were evaluated pre- and postoperatively using the modified Merle d'Aubigné-Postel (18-point) scale, the International Knee Documentation Committee (IKDC) pain, function, and total scores, and the Knee Society function (KS-F) score. Patient satisfaction was assessed at latest follow-up., Results: Seventeen of the 28 knees (60.7%) had further surgery after the OCA transplantation; 8 of the 28 knees (28.6%) were considered OCA failures (4 conversions to total knee arthroplasty, 2 conversions to patellofemoral knee arthroplasty, 1 revision OCA, 1 patellectomy). Patellar allografting survivorship was 78.1% at 5 and 10 years and 55.8% at 15 years. Among the 20 knees (71.4%) with grafts in situ, the mean follow-up duration was 9.7 years (range, 1.8-30.1 years). Pain and function improved from the preoperative visit to latest follow-up, and 89% of patients were extremely satisfied or satisfied with the results of the OCA transplantation., Conclusion: OCA transplantation was successful as a salvage treatment procedure for cartilage injuries of the patella., (© 2015 The Author(s).)

Background: Osteochondral allograft (OCA) transplantation is an effective treatment option for chondral and osteochondral defects of the knee., Hypothesis: Patients treated with OCAs for reciprocal bipolar lesions of the knee would demonstrate significant clinical improvement., Study Design: Case series; Level of evidence, 4., Methods: Between 1983 and 2010, OCAs were implanted for bipolar chondral lesions in 46 patients (48 knees). The 21 male and 25 female patients averaged 40 years of age (range, 15-66 years). Thirty-four lesions were tibiofemoral, and 14 were patellofemoral. Forty-two knees (88%) had undergone a mean of 3.4 previous surgeries (range, 1-8). The mean allograft area was 19.2 cm(2). Clinical evaluation included the modified Merle d'Aubigné-Postel (18-point), International Knee Documentation Committee (IKDC) pain and function, and Knee Society function (KS-F) scores. Further surgeries on the operative joint were documented., Results: Survivorship of the bipolar OCA was 64.1% at 5 years. Thirty knees underwent further surgery; 22 knees (46%) were considered failures (3 OCA revisions, 14 total knee arthroplasties, 2 unicondylar arthroplasties, 2 arthrodeses, and 1 patellectomy). Among patients whose OCA was still in situ at follow-up, the mean follow-up was 7 years (range, 2.0-19.7 years). The mean 18-point score improved from 12.1 to 16.1; 88% (23/26 knees) of surviving allografts scored ≥15. The mean IKDC pain score improved from 7.5 to 4.7, and the mean IKDC function score improved from 3.4 to 7.0. The mean KS-F score improved from 70.5 to 84.1., Conclusion: Osteochondral allograft transplantation is a useful salvage treatment option for reciprocal bipolar cartilage lesions of the knee. High reoperation and failure rates were observed, but patients with surviving allografts showed significant clinical improvement., (© 2015 The Author(s).)

Osteochondral defects represent a serious clinical problem. Although the cell-scaffold complexes have been reported to be effective for repairing osteochondral defects, a periosteal flap is frequently needed to arrest leakage of the implanted cells into the defect and to contribute to the secretion of cytokines to stimulate cartilage repair. The electrospun mesh mimicking the function of the flap assists tissue regeneration by preventing cell leakage and merits favorable outcomes in the cartilaginous region. In this study, an oriented poly(ε-caprolactone) (PCL) fibrous membrane (OEM) was fabricated by electrospinning as a periosteal scaffold and then freeze-dried with a collagen type I and hyaluronic acid cartilage scaffold (CH) and finally, freeze-dried with a tricalcium phosphate (TCP) bone substratum. Scanning electron microscopic images show obvious microstructure formation of the trilayered scaffolds, and electrospun fibrous membranes have an oriented fibrous network structure for the periosteal phase. Also shown are opened and interconnected pores with well designed three-dimensional structure, able to be bound in the CH (chondral phase) and TCP (osseous phase) scaffolds. In vitro results showed that the OEM can promote the orientation of bone marrow mesenchymal stem cell (BMSCs) and BMSCs can penetrate into the CH and TCP. After successfully combining the BMSCs, the tissue-engineered cartilage which contained the OEM and TCP complex was successfully used to regenerate the osteochondral defects in the rabbit model with greatly improved repair effects., (© 2014 Wiley Periodicals, Inc.)

Background: Multiple studies in adults have shown that osteochondral allograft transplantation is an effective treatment option for large chondral and osteochondral defects of the knee. Limited outcome data are available on osteochondral allografts in the pediatric and adolescent patient populations., Purpose: To describe a 28-year experience with osteochondral allograft transplantation in patients younger than 18 years with a focus on subjective outcome measures, return to activities, and allograft survivorship., Study Design: Case series; Level of evidence, 4., Methods: A total of 39 patients (43 knees) underwent fresh osteochondral allograft transplantation for treatment of chondral and osteochondral lesions. Twenty-six male and 17 female knees with a mean age of 16.4 years (range, 11.0-17.9 years) at index surgery were followed-up at a mean of 8.4 years (range, 1.7-27.1 years). Thirty-four knees (79%) had at least 1 previous surgery. The most common underlying causes of the lesions were osteochondritis dissecans (61%), avascular necrosis (16%), and traumatic chondral injury (14%). Mean allograft size was 8.4 cm(2). The most common allograft location was the medial femoral condyle (41.9%), followed by the lateral femoral condyle (35%). Each patient was evaluated with the International Knee Documentation Committee pain, function, and total scores; a modified Merle d'Aubigné-Postel (18-point) scale; and Knee Society function score. Failure was defined as revision osteochondral allograft or conversion to arthroplasty., Results: Five knees experienced clinical failure at a median of 2.7 years (range, 1.0-14.7 years). Four failures were salvaged successfully with another osteochondral allograft transplant. One patient underwent prosthetic arthroplasty 8.6 years after revision allograft. Graft survivorship was 90% at 10 years. Of the knees whose grafts were in situ at latest follow-up, 88% were rated good/excellent (18-point scale). The mean International Knee Documentation Committee scores improved from 42 preoperatively to 75 postoperatively, and the Knee Society function score improved from 69 to 89 (both P < .05). Eighty-nine percent of patients reported "extremely satisfied" or "satisfied.", Conclusion: With 88% good/excellent results and 80% salvage rate of clinical failures with an additional allograft, osteochondral allograft transplantation is a useful treatment option in pediatric and adolescent patients.

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

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]

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]

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]

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.

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]

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]

This study was performed to evaluate the effect of teriparatide therapy on the healing of osteochondral defects of the mandibular condylar. Ninety-six rats underwent surgery to create a defect in the condylar head on one side of the mandible, and were divided into two groups. One group received subcutaneous injection of 2 µg/kg/day teriparatide, and the other group received normal saline until sacrifice. On postoperative days 20, 40, and 60, 16 animals from each group were sacrificed, and bone and cartilage healing was histologically evaluated and semiquantitatively scored (1-5). The mean difference in healing score of the cartilaginous and subchondral parts of the defect between the teriparatide and control groups at days 20, 40 and 60 were 0.438 and 0.438, 0.813 and 0.750, and 1.125 and 0.813, respectively. The healing scores of the osteochondral defects in the teriparatide group were significantly (p< 0.05) higher than that in the control group at days 40 and 60. This study has shown beneficial effects of teriparatide on the healing of condylar osteochondral defects in rats. Clinical trials are required to extrapolate these findings to humans. [ABSTRACT FROM AUTHOR]

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]

Now it is possible to combine the different biomaterial properties of graphene and 3 D printing scaffolds produced by tissue engineering for cartilage repair. In the study graphene-containing (1, 3, 5, 10 wt%), porous and oriented poly-ε-caprolactone-based scaffolds were prepared by robocasting method to use in the regeneration of large osteochondral defects. The scaffolds were implanted into the full-thickness osteochondral defect in a rabbit model to evaluate the regeneration of the defect in vivo. For this purpose, twenty female New Zealand white rabbits were used and they were euthanized at 4 and 8 weeks of implantation. The reparative osteochondral tissues were harvested from rabbit distal femurs and then processed for gross appearance assessment, radiographic imaging, histopathological, histochemical and immunohistochemical examinations. Results revealed that graphene-containing graft materials caused significant amelioration at the defect areas. Graphene-containing graft materials improved the fibrous, chondroid and osseous tissue regeneration compared to the control group. The expressions of bone morphogenetic protein-2 (BMP-2), collagen-1 (col-1), vascular endothelial growth factor (VEGF) and alkaline phosphatase (ALP) expressions were more prominent in graphene-containing PCL implanted groups (p <.001). Picrosirrius red method was used for to evaluate connective and muscle tissues. Results also revealed that the ameliorative effect of graphene increased by the elevation in concentration. The most prominent healing was observed in 10 wt% graphene-containing PCL based composite scaffold implanted group. This study results showed that graphene-containing PCL scaffolds enhanced the healing significantly in large osteochondral defect areas compared to the control groups. [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]

Background: Various cell-free scaffolds are already in use for the treatment of osteochondral defects (OCDs); however, a gold standard material has not yet been defined. Purpose: This study compared the macroscopic, histological, and scanning electron microscopy (SEM) characteristics of Chondro-Gide (CG), MaioRegen (MA), and poly- d, l -lactide-co-caprolactone (PLCL) cell-free scaffolds enhanced with small-diameter microfractures (SDMs) for OCDs in a rabbit model. Study Design: Controlled laboratory study. Methods: In total, 54 knees from 27 rabbits were used in this study. Three rabbits were sacrificed at the beginning of the study to form an intact cartilage control group (group IC). An OCD model was created at the center of the trochlea, and SDMs were generated in 24 rabbits. Rabbits with OCDs were divided into 4 groups (n = 12 knees per group) according to the cell-free scaffold applied: CG (group CG), MA (group MA), PLCL (group PLCL), and a control group (group SDM). Half of the rabbits were sacrificed at 1 month after treatment, while the other half were sacrificed at 3 months after treatment. Healed cartilage was evaluated macroscopically (using International Cartilage Regeneration & Joint Preservation Society [ICRS] classification criteria) and histopathologically (using modified O'Driscoll scores and collagen staining). Additionally, cell-free scaffold morphologies were compared using SEM analysis. Results: ICRS and modified O'Driscoll classification and staining with collagen type 1 and type 2 demonstrated significant differences among groups at both 1 and 3 months after treatment (P <.05). The histological characteristics of the group IC samples were superior to those of all other groups, except group PLCL, at 3 months after treatment (P <.05). In addition, the histological properties of group PLCL samples were superior to those of group SDM samples at both 1 and 3 months after treatment in terms of the modified O'Driscoll scores and type 1 collagen staining (P <.05). Concerning type 2 collagen staining intensity, the groups were ranked from highest to lowest at 3 months after treatment as follows: group PLCL (30.3 ± 2.6) > group MA (26.6 ± 1.2) > group CG (23.3 ± 2.3) > group SDM (18.9 ± 0.9). Conclusion: OCDs treated with enhanced SDM using cell-free PLCL scaffolds had superior histopathological and microenvironmental properties, more hyaline cartilage, and more type 2 collagen compared with those treated using CG or MA scaffolds. Clinical Relevance: OCDs treated with PLCL cell-free scaffolds may have superior histopathological properties and contain more type 2 collagen than do OCDs treated with CG or MA cell-free scaffolds. [ABSTRACT FROM AUTHOR]

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

Copyright of Turkish Journal of Trauma & Emergency Surgery / Ulusal Travma ve Acil Cerrahi Dergisi is the property of KARE Publishing and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

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.

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

Osteochondral defects are relatively common in weight-bearing joints of the lower extremities and require multiple approaches of treatment. This work is focused on designing three-dimensional (3D) bilayered scaffolds fully integrating a top chitosan/hydroxypropylmethyl cellulose layer (CS/HPMC) mimicking cartilage and a bottom chitosan/hydroxypropylmethyl cellulose/nano-hydroxyapatite layer (CS/HPMC/nHAp) imitating bone for the treatment of osteochondral defects prepared by freeze drying. Additionally, an anti-inflammatory drug (in the bottom layer) and an antibiotic drug (in the top layer) are incorporated in the form of microspheres and nanofibers, respectively, into these scaffolds to diminish/prevent post-surgical inflammation/infection through sustained release of the drugs. The scaffolds were characterized by a variety of techniques. FT-IR analysis confirmed that there is no/weak interactions between the components, SEM images showed that both layers of the scaffolds have homogenous pore distribution, and scaffolds exhibited reproducible swelling and degradation behavior. Drug release was shown to take place over a period of 14 days in PBS. The scaffolds supported the growth and proliferation of MC3T3 pre-osteoblast cells in vitro and have potential for use in vivo application in the future. [ABSTRACT FROM AUTHOR]

• Eu-doped HAp nanorods are successfully synthesized via hydrothermal method. • GelMA/Eu-HAp nanocomposite hydrogel functions through immunoregulation. • Eu-HAp nanorods facilitate tissue repair through CDH5-RAS-RAF-MEK-ERK-CSF1 axis. • The treatment outcome of Eu-HAp nanorods for OA and osteochondral defect is proved. Osteoarthritis (OA) remains an unsolved clinical problem characterized by cartilage degradation and subchondral bone remodeling. Most studies have focused on cartilage lesions, while rare effective strategies have been developed to reconstruct osteochondral defects simultaneously. Moreover, cartilage regeneration under inflammatory conditions is even more limited. M1/M2 macrophage imbalance has been demonstrated to be a crucial player in the inflammatory microenvironment. Accordingly, immunoregulation during OA progression may be a promising method to create a favorable microenvironment for the efficient repair of cartilage and subchondral bone lesions. Herein, we developed new europium (Eu)-doped hydroxyapatite (HAp) nanorods that could simultaneously mediate the differentiation of chondrocytes and BMSCs to facilitate both cartilage and subchondral bone regeneration. Innate immunity participates in Eu-HAp-mediated tissue regeneration, and a comprehensive CDH5-RAS-RAF-MEK-ERK-CSF1 axis is critical in the crosstalk between biomaterials, immune cells, and effector cells. The GelMA/Eu-HAp nanocomposite hydrogel system is first successfully fabricated, and the treatment outcome in an osteochondral defect model is confirmed. Overall, our findings uncover the positive regulation of Eu-HAp nanorods in cartilage-related lesions by inhibiting inflammation and creating a regenerative microenvironment. This study may inspire the concept of developing next-generation nanomaterials with ion-doping properties and provide novel insight for treating compound defects in inflammatory diseases. [ABSTRACT FROM AUTHOR]

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

Background: It is unclear whether chondral fragments without bone have the potential to heal after fixation. Controversy exists and opinions differ regarding the optimal treatment of chondral defects after pure chondral fracture. Purpose: To determine clinical and radiographic outcomes after internal fixation of traumatic chondral fragments repaired to bone in the knee. Study Design: Case series; Level of evidence, 4. Methods: A retrospective clinical and radiographic evaluation of 10 male patients with a mean age of 14.6 years (range, 10-25 years) at the time of surgery was performed. Eight of 10 patients were skeletally immature. Patients were selected by operating surgeons per the presence of a large displaced pure chondral fragment on magnetic resonance imaging and confirmed on intraoperative inspection. All patients had a diagnosed traumatic displaced pure chondral fracture of the knee (without bone) and underwent internal fixation with minimum 1-year follow-up. Validated patient-reported and surgeon-measured outcomes were collected pre- and postoperatively. All patients were evaluated at a mean 56 months postoperatively. Results: At surgery, the mean defect size that was primarily repaired with the displaced chondral fragment was 1.9 × 2.0 cm. With minimum 1-year follow-up, there were no clinical failures. All 8 patients who had subsequent magnetic resonance imaging follow-up had radiographic evidence of complete healing of the chondral fragment back to bone. At a mean follow-up of 56 months (range, 13-171 months; median, 36 months), patients had a mean International Knee Documentation Committee score of 94.74 (range, 87.4-100), a mean Marx Activity Scale score of 14.4 (range, 8-16), and a mean Tegner Activity Scale score of 7 (range, 5-9). At final follow-up, all patients except 1 returned to sports. Conclusion: The treatment of large traumatic chondral fragments is controversial. In this select series of 10 young patients who underwent primary repair with internal fixation, there were no failures clinically. Patients demonstrated excellent short-term clinical and radiographic results after fixation of these relatively large chondral fragments in the knee. [ABSTRACT FROM AUTHOR]

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Abstract Background Osteochondral knee defects (OCD) are often symptomatic, causing pain and functional impairment even in young and active patients. Regenerative surgical options, aiming to stimulate natural cartilage healing, have been recently used as a first line treatment. In this study, a new hydrogel is investigated in its capacity to regenerate the ultra-structural quality of hyaline cartilage when combined with a classical microfracture technique. Material and methods Forty-six patients, affected by grade III and IV knee chondropathies, were consecutively treated between 2013 and 2015 with microfractures followed by application of a modern hydrogel in the lesion site. All patients underwent clinical evaluation (WOMAC) pre-operatively, at 6,12 and at 24 months postoperatively: the results were compared with a subsequent, consecutive, matched, control group of 23 patients treated with microfractures alone. In a parallel and separate in-vitro histological study, adipose derived mesenchymal stem cells (ADMSCs) were encapsulated in the hydrogel scaffold, induced to differentiation into chondrocytes, and observed for a 3 weeks period. Results The initial WOMAC score of 58.6 ± 11.0 in the study group was reduced by 88% at 6 months (7.1 ± 9.2) and 95% at 24 months (2.9 ± 5.9). The "in-vitro" study revealed a histological characterization typical of hyaline cartilage in study group. Separate biopsies performed at 12 months post-op in the study group also revealed type 2 collagen and hyaline-like cartilage in the regenerated tissue. Conclusion Our study demonstrated high patient satisfaction rates after microfractures combined with a modern hydrogel scaffold; histologic evaluation supported the hypothesis of creating an enhanced chondrogenic environment. Microfracture "augmentation" using modern acellular biomaterials, like hydrogels, might improve the clinical outcomes of this classical bone marrow stimulating procedure. [ABSTRACT FROM AUTHOR]

Introduction: Osteochondral defects of the knee may cause functional impairment of young and sportively active patients. Different surgical treatment options have been proposed using either one or two step procedures. The aim of the current study was to evaluate mid-term outcomes of combined bone grafting with autologous matrix-associated chondrogenesis (AMIC) for the treatment of large osteochondral defects.Materials and Methods: 15 Patients with osteochondrosis dissecans of the medial femoral condyle grade III or IV according to ICRS classification were treated with a single step surgical procedure combining bone grafting and the AMIC procedure. Mean defect size was 4.98 cm2 (± 3.02) and patients were examined at 6, 12 weeks, 6 and 12 month and at mean final follow-up of 49 months (36-61). Patients were evaluated using VAS, IKDC, KOOS, Lysholm, Tegner activity scores and psychological and physical health assessed using the SF 12. MRI evaluation was performed at final follow-up using the MOCART score.Results: Pain had significantly decreased at final follow-up (7.2 ± 1.4 vs. 2.4 ± 2.6) compared to preoperative baseline. All functional scores had improved significantly throughout the follow-up period (IKDC from 36.6 ± 20.6 vs. 72.2 ± 18.7; KOOS 50.0 ± 18.9 vs. 81.7 ± 13.9; LYSHOLM 39.3 ± 19.5 vs. 79.8 ± 15.1). SF12 evaluation showed a significant increase in physical component summary (PCS) (31.2 ± 11.1 preoperative vs. 46.3 ± 9.9 at final follow-up), while mental component summary (MCS) remained stable (51.8 ± 8.9 vs. 57.3 ± 3.3). MOCART score revealed a mean overall score of 77 ± 15 at final follow-up. Integration to the adjacent cartilage was complete in 79%, incomplete in 21%. Defect filling was complete in 64%, incomplete in 36%.Conclusion: Significant improvement of knee function and restoration of homogenous cartilage morphology could be achieved with simultaneous AMIC procedure and bone grafting in 2/3 of all patients with large osteochondral lesions at 4 years postoperatively. [ABSTRACT FROM AUTHOR]

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Introduction: Articular cartilage lesions of the hip are difficult to effectively treat. Osteochondral allograft (OCA) transplantation in the knee has been associated with long-term success, but OCA for the hip has not been extensively studied. Here, we present the clinical and radiological outcomes from a cohort of 10 patients treated with fresh OCA transplants for large osteochondral defects of the femoral head and/or acetabulum. Methods: 10 patients who had undergone osteochondral allograft transplantation of the femoral head and/ or acetabulum at our institution between 2013 and 2016 were identified from our Institutional Review Boardapproved registry. Hip disability and Osteoarthritis Outcome Score (HOOS) was used to track patient progress. Results: 10 patients with an average clinical follow-up of 1.4 years were included in this study. 4 patients were treated solely with OCA plugs for femoral head defects, while the remaining 6 received femoral OCA plugs and at least 1 concomitant procedure for additional intraarticular pathology. 7 patients (70%) had successful functional outcomes, while 3 (30%) had unsuccessful outcomes and were subsequently converted to total hip arthroplasty (THA) 5 to 29 months after OCA. Conclusions: OCA transplantation can be an effective treatment strategy for young, healthy individuals with ar- ticular cartilage lesions of the hip. Smoking, avascular necrosis aetiology, acetabular involvement and concomitant procedures may be risk factors for unsuccessful outcomes necessitating salvage with THA. Long-term clinical studies to refine indications and determine functional outcomes and survival rates are warranted. [ABSTRACT FROM AUTHOR]

Objective: To investigate the effect of decellularized osteochondral extracellular matrix (ECM) scaffold for osteochondral defect regeneration.Design: We compared the histological features and microstructure of degenerated cartilage to normal articular cartilage. We also generated and evaluated osteochondral ECM scaffolds through decellularization technology. Then scaffolds were implanted to osteochondral defect in rabbit model. After 12 weeks surgery, regeneration tissues were analyzed by histology, immunohistochemistry evaluation. And possible mechanisms of angiogenesis and cell migration were explored.Results: We demonstrated decreased cell numbers, formation of fibrous cartilage, lost microstructure and worse permeability in degenerated cartilage compared to normal cartilage. We also generated an osteochondral ECM scaffold with a hierarchical structure that exhibited low immunogenicity, high bioactivity, and well biocompatibility. We found that the ECM scaffold promoted tissue regeneration in osteochondral defects, which was dependent on the scaffold constituents and stratified three-dimensional microstructure as well as on its ability to inhibit angiogenesis and stimulate cell migration.Conclusions: Our findings demonstrated that the biphasic hierarchical ECM scaffold represents a novel and effective biomaterial that can be used in the treatment of osteochondral defect. [ABSTRACT FROM AUTHOR]

Osteochondral defects (OCDs) of the talus remain a surgical challenge, especially after failed primary treatment. The aim of the present study was to examine the clinical outcomes after HemiCAP ® implantation for OCDs of the medial talar dome after failed previous surgery. Our retrospective study included 11 patients, who had undergone surgery from June 2009 to September 2012 for an OCD of the medial talar dome and received a HemiCAP ® on the talus after failed previous surgery for OCD. The data were acquired using patients’ medical records and standardized questionnaires, including the Foot and Ankle Outcome Score (FAOS), University of California at Los Angeles (UCLA) activity score, EQ-5D, numerical rating scale (NRS), and Short-Form 36-item Health Survey (SF-36). Using these scores, the possibility of returning to work and sports was determined. Any complications and the need for revision surgery were recorded. One patient refused to participate in the study, leaving 10 patients for evaluation. The mean age was 47.64 ± 10.97 years. The mean follow-up period was 43.5 ± 35.51 months. The FAOS and SF-36 subscale scores and the EQ-5D and UCLA activity scores did not improve significantly ( p < .05). The mean postoperative pain score on the NRS improved significantly from 6.6 ± 1.77 preoperatively to 5.1 ± 2.02 postoperatively ( p < .05). A greater body mass index led to worse postoperative outcomes with higher scores on the pain-NRS and less satisfaction ( p < .05). Ten revisions for ongoing pain were performed in 7 patients (70.0%) within a mean of 28.4 ± 13.35 months of the initial procedure, and 6 patients (60%) indicated they would undergo surgery again. The results of the present study have shown that implantation of the HemiCAP ® as a salvage procedure for OCDs of the talus is challenging and does not consistently lead to good clinical results. Also, overweight patients appear to have an increased risk of postoperative dissatisfaction and persistent ankle pain. [ABSTRACT FROM AUTHOR]

The present study was designed to assess the role of TGF-β1 in cartilage repair in an in vivo model of articular cartilage defect in rabbit. Twenty four New Zealand white rabbits of either sex, 6-7 months old (1-2 kgs) were divided into two groups i.e. A (Control) or B (TGF-β1). The articular cartilage defect of 3mm diameter and 2mm depth was created in the femoral groove of femoropatellar joint. Animals of both the groups were provided with collagen scaffolds at 10μg/cm2 in the articular defect. However, Group B animals were further provided with 20ng/20μl of TGF- β1 in the defect stuffed with collagen scaffold. Articular defect grossly appeared re-surfaced completely and healed with better joint movement in group B as compared to the animals of group A. Repaired articular surface maintained the transparency and sheen as hyaline cartilage. Synthesis of proteoglycans, enhanced filapodia activity, significant increase in the collagen type II and aggrecan in the repaired tissue further supports that TGF-β1 at the tested dosage improved the articular cartilage management and repair.

INTRODUÇÃO E OBJETIVOS: Existem várias formas de tratamento das perdas extensas de substância osteocondral (OC), entre elas, a mosaicoplastia recoberta com periósseo (mosaicambium). Neste trabalho pretende-se avaliar os resultados clínicos a médio dos doentes com defeito osteocondral tratados por esse método. MÉTODOS: Vinte joelhos com defeito osteocondral superior a 2cm² foram operados entre 1999 e 2005, com recurso a duas técnicas cirúrgicas (mosaicoplastia/mosaicambium). Todos os doentes foram avaliados em pré-operatório clinicamente (escalas ICRS, VAS), radiograficamente e com RM. No ano de 2008 todos foram revistos e avaliados seguindo os mesmos critérios. Os casos foram distribuídos em dois grupos consoante o tipo de tratamento. A avaliação estatística recorreu ao programa informático EPI2000. Utilizou-se o teste do qui-quadrado para variáveis categoriais e o teste t de Student para variáveis contínuas. Aceitou-se como erro alfa um valor de 0,05. Tipo de estudo: Estudo clínico, retrospectivo, nível de evidência 4. RESULTADOS: Antes, todos os doentes estavam nos grupos ICRS C e D. Em 2008, 18 doentes estavam nos grupos A e B (12 no grupo A). Comparando os resultados entre grupos (mosaicoplastia/mosaicambium), não houve diferenças significativas entre os grupos. Radiograficamente, não existiam alterações em 55% dos casos. DISCUSSÃO: Sem diferenças clínicas, por que a opção mosaicambium? A morbilidade nas zonas dadoras não é desprezível. A opção mosaicambium recorreu a menos cilindros OC, reduzindo a morbilidade resultante. CONCLUSÃO: A técnica mosaicambium é uma boa opção alternativa para perdas de substância OC com mais de 2 cm².INTRODUCTION AND OBJECTIVES: Clinical and functional assessment comparing cases of full-thickness chondral defects (OC) treated with mosaicplasty or mosaicplasty covered with periosteum (mosaicambium). METHODS: 20 knees with chondral defect, (10 mosaicplasty/10 mosaicambium) were operated between 1999 and 2005. All patients were clinically assessed preoperatively using the ICRS scale, VAS scale, X-ray and MRI. During 2008, we reviewed patients using the same protocol. For statistical purposes, the patients were divided into two groups, according to the surgical technique. Statistical analysis was performed with EPI2000 program, using chi-squared test and Student's t test, with a significance level of 0.05. RESULTS: Preoperatively, all patients were in group C /D (ICRS scale). In 2008, 18 cases were in groups A and B according to the ICRS scale (12 in A). Between groups, there were no statistical differences. The X-ray study revealed no changes in 55% of cases. DISCUSSION: With no differences, why mosaicambium option? Morbidity on graft donor zones is not negligible. Mosaicambium uses less chondral grafts, reducing the potential for morbidity at graft donor zones. CONCLUSION: The mosaicambium technique is an excellent alternative for chondral defects greater than 2 cm².

We investigated the effect of low-intensity pulsed ultrasound (LIPUS) treatment combined with mesenchymal stromal cell (MSC) injection for cartilage repair and subchondral bone reconstitution for treatment of osteochondral defects. An osteochondral defect was created on both femur grooves of Wistar rats. Four weeks later, bone marrow MSCs were injected into the right knee joint. The rats were divided into two intervention groups: without or with LIPUS irradiation. Cartilage repair was evaluated histologically based on the Wakitani cartilage repair score. Subchondral bone reconstitution was evaluated as bone volume (BV)/tissue volume (TV) by micro-computed tomography analysis. MSC injection improved the cartilage repair score, and LIPUS irradiation improved BV/TV. Combination treatment promoted both cartilage repair and BV/TV improvement. Thus, MSC injection combined with LIPUS irradiation is more effective than either treatment alone in promoting concurrent cartilage repair and subchondral reconstitution. [ABSTRACT FROM AUTHOR]

Background: Widespread adoption of fresh allograft transplantation remains limited, predominantly by supply issues. To overcome these limitations, a preshaped, cylindrical sterilized and decellularized osteochondral allograft (SDOCA) implant was recently introduced as a clinical treatment option. Purpose: To evaluate functional outcomes and graft survivorship among patients treated with the SDOCA implant for knee cartilage injuries. Study Design: Case series; Level of evidence, 4. Methods: An institutional review board–approved database was used to identify a series of patients with prospectively collected data who had been treated with the SDOCA implant. The surgeries were performed at 2 centers by 2 surgeons. Patient-reported outcomes, magnetic resonance imaging (MRI), and the number and type of reoperations were assessed. Failure was defined as structural damage of the graft diagnosed by arthroscopy or MRI, and any reoperation resulting in removal of the allograft. Patients were evaluated pre- and postoperatively using the Knee injury and Osteoarthritis Outcome Score (KOOS) and Marx Sports Activity Scale. MRI was assessed preoperatively and postoperatively. Results: There were 32 patients with a mean age (±SD) of 35.1 ± 10.6 years; 59% were male. Twenty-three (72%) knees had previous surgery. The mean defect area (±SD) was 2.9 ± 2.0 cm2, and the mean allograft size was 13.18 ± 2.3 mm (6 grafts ≤9 mm and 59 grafts ≥11 mm). The median number of allografts per knee was 2 (range, 1-5 grafts). Twenty-three of the 32 knees (72%) were considered failures by the definition detailed above. Of these, 14 knees (43%) had further surgery after the index procedure. Implant survivorship was 19.6% at 2 years. The mean follow-up duration was 1.29 years (range, 0.11-2.8 years). KOOS pain, activities of daily living (ADL), sports and recreation (sport/rec), and knee-related quality of life improved significantly from the preoperative visit to latest follow-up. Age was significantly predictive of failure, with a hazard ratio of 1.68 per 1 SD older (95% CI, 1.05-2.68; P = .030). The MOCART (magnetic resonance observation of cartilage repair tissue) feature effusion was the only score to correlate with KOOS (symptoms, pain, ADL, sport/rec). Conclusion: The SDOCA implant demonstrated a 72% failure rate within the first 2 years of implantation at these 2 institutions. [ABSTRACT FROM AUTHOR]

Background: The common purpose of almost all methods used to treat the osteochondral injuries is to produce a normal cartilage matrix. However current methods are not sufficient to provide a normal cartilage matrix. For that reason, researchers have studied to increase the effectiveness of this methods using chondrogenic and chondroprotective molecules in recent experimental studies. Insulin-like growth factor-1 (IGF-1) and hyaluronic acid (HA) are two important agents used in this field. This study compared the effects of IGF-1 and HA in an experimental osteochondral defect in rat femora. Materials and Methods: The rats were divided into three groups (n = 15 per group) as follows: The IGF-1 group, HA group, and control group. An osteochondral defect of a diameter of 1.5 mm and a depth of 2 mm was created on the patellar joint side of femoral condyles. The IGF-1 group received an absorbable gelatin sponge soaked with 15 µg/15 µl of IGF-1, and the HA group received an absorbable gelatin sponge soaked with 80 µg HA. The control group received only an absorbable gelatin sponge. Rats were sacrificed at the 6th week, and the femur condyles were evaluated histologically. Results: According to the total Mankin scale, there was a statistically significant difference between IGF-1 and HA groups and between IGF-1 and control groups. There was also a significant statistical difference between HA and control groups. Conclusion: It was shown histopathologically that IGF-1 is an effective molecule for osteochondral lesions. Although it is weaker than IGF-1, HA also strengthened the repair tissue. [ABSTRACT FROM AUTHOR]

Introduction: Treatment of osteochondral injuries is challenging, and no gold standard has been established. Layered cell-free scaffolds are a new treatment option for these defects. The aim of this study was to evaluate the osteochondral repair in patients treated with the MaioRegen(®) scaffold, a cell-free biomimetic scaffold consisting of type I collagen and hydroxyapatite. Treatment using this scaffold has previously shown promising clinical results.Methods: Ten patients with osteochondral lesions in the knee (n = 6) or in the talus (n = 4) were enrolled. The patients underwent pre-operative MRI and CT scans and were assessed at 1- and 2.5-year timescales post-operatively. The cartilage and bone formations were evaluated semi-quantitatively using the MOCART score. Knee patients were clinically evaluated using KOOS, subjective IKDC and Tegner scores, whereas ankle patients were evaluated using AOFAS Hindfoot and Tegner scores.Results: Two patients were re-operated and excluded from further follow-up due to treatment failure. None of the patients had complete regeneration of the subchondral bone evaluated using CT. At 2.5 years, 6/8 patients had no or very limited (<10 %) bone formation in the defects and 2/8 had 50-75 % bone formation in the treated defect. MRI showed no improvement in the MOCART score at any time point. The IKDC score improved from 41.3 to 80.7, and the KOOS pain subscale improved from 63.8 to 90.8 at 2.5-year follow-up. No improvement was found with the remaining KOOS subscales, the Tegner or AOFAS Ankle-Hindfoot score.Conclusion: Treatment of osteochondral defects in the ankle and knee joint with a biomimetic scaffold resulted in incomplete cartilage repair and poor subchondral bone repair at 1- and 2.5-year follow-up. Clinical significant improvements were observed. These results raise serious concerns about the biological repair potential of the MaioRegen(®) scaffold, and we advise to use the MaioRegen(®) scaffold with caution.Level Of Evidence: Prospective therapeutic study, Level IV. [ABSTRACT FROM AUTHOR]

Purpose: To evaluate sporting activity following osteochondral autologous transfer (OAT) combined with valgus high tibial osteotomy (HTO) in young and active patients with focal osteochondral defects of the medial femoral condyle and concomitant varus malalignment.Methods: Thirty patients with focal osteochondral defects of the medial femoral condyle and varus malalignment >2° were enrolled. All patients were active in sports on a regular base prior to surgery (lifetime), but were unable to perform sports at the time of surgery. Sporting activity 1 year preoperatively and at final follow-up was compared using a previously published sports questionnaire, which assesses sports level, number of sports disciplines, sports frequency, sports duration and the participation in 32 common sports disciplines. Additionally, the Tegner activity scale and the Activity Rating Scale were used.Results: After a mean follow-up of 6.9 years (2.5-9.8; SD 2.4), 76.7 % of patients were participating in sports on a regular basis (Fig. 2). Compared to 1 year preoperatively, there was no difference (n.s.) with regard to sports, the number of sports disciplines, sports frequency and sports duration (Fig. 4). The median Tegner activity scale measured preoperatively 5.0 (2.0-7.0) and post-operatively 5.0 (4.0-7.0) points (Fig. 3), and the ARS changed from 5.7 to 5.3 points (n.s.). The different types of sports disciplines were comparable between 1 year preoperatively and at follow-up.Conclusion: A high return to sports rate and an activity level comparable to the state at 1 year preoperatively can be expected in young and active patients after combined OAT and valgus HTO. This seems to be relevant in clinical practice when planning, indicating and performing these complex procedures.Level Of Evidence: IV. [ABSTRACT FROM AUTHOR]

[Display omitted] • In this study, a bioactive biomimetic multiphasic scaffold fabricated through decellularization and porosity optimization was highly biomimetic in the true sense, simulating the structure and mechanical properties of a native osteochondral unit. • The innovation of this study lies in the construction of an osteochondral scaffold with a remarkable repair effect through a series of simple and inexpensive techniques. • The method of this study can be used to obtain scaffolds that can be stored commercially in a ready-to-use state, with clinical applications and commercial prospects. 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. [ABSTRACT FROM AUTHOR]