Osteochondral Defects Research Articles

Effect of Passaging on Bovine Chondrocyte Gene Expression and Engineered Cartilage Production.

Tissue engineering strategies show great potential for repairing osteochondral defects in osteoarthritic joints; however, these approaches often rely on passaging cells multiple times to obtain enough cells to produce functional tissue. Unfortunately, monolayer expansion culture causes chondrocyte dedifferentiation, which is accompanied by a phenotypical and morphological shift in chondrocyte properties that leads to a reduction in the quality of de novo cartilage produced. Thus, the objective of this study was to evaluate transcriptional variations during in vitro expansion culture and determine how differences in cell phenotype from monolayer expansion alter development of functional engineered cartilage. We used an unbiased approach to explore genome-wide transcriptional differences in chondrocyte phenotype at passage 1 (P1), P3, and P5, and then seeded cells into hydrogel scaffolds at P3 and P5 to assess cells' abilities to produce cartilaginous extracellular matrix in three dimensional (3D). We identified distinct phenotypic differences, specifically for genes related to extracellular organization and cartilage development. Both P3 and P5 chondrocytes were able to produce chondrogenic tissue in 3D, with P3 cells producing matrix with greater compressive properties and P5 cells secreting matrix with higher glycosaminoglycan/DNA and collagen/DNA ratios. Furthermore, we identified 24 genes that were differentially expressed with passaging and enriched in human osteoarthritis (OA) genome-wide association studies, thereby prioritizing them as functionally relevant targets to improve protocols that recapitulate functional healthy cartilage with cells from adult donors. Specifically, we identified novel genes, such as TMEM190 and RAB11FIP4, which were enriched with human hip OA and may play a role in chondrocyte dedifferentiation. This work lays the foundation for several pathways and genes that could be modulated to enhance the efficacy for chondrocyte culture for tissue regeneration, which could have transformative impacts for cell-based cartilage repair strategies.

Cell-free biomimetic scaffold for chondral and osteochondral lesions: surgical technique for custom and standardized implantation

IntroductionCell-free chondral and osteochondral scaffolds have been introduced to address lesions of the articular surface. A proper implantation technique is key to favor scaffold integration, regenerative processes, and positive clinical outcomes. ObjectivesThe purpose of this article is to describe indications and surgical steps for both the custom traditional free-hand implantation approach and an innovative minimally invasive technique for the standardized implantation of this biomimetic cell-free scaffold (MaioRegen; Fin-Ceramica Faenza Spa). MethodsIndications and contraindications for this scaffold implantation have been provided. The required steps for surgical preparation, implantation technique, and postoperative management have been described as well to address articular surface lesions of the knee. ResultsA dedicated instrumentation for circular implants of different sizes has been developed to allow more precise preparation of the depth and width of the defect, reducing the invasiveness and increasing implant stability. The custom free-hand technique with chisels and osteotomes remains useful when the lesion does not allow the use of the standardized instrumented technique. In case further stability of the implant is needed, fibrin glue addition should be considered. ConclusionsBy guiding the readers with the key perioperative and intraoperative steps, chondral and osteochondral defects can be addressed with the use of a cell-free scaffold, maximizing implant stability.

Ex vivo storage of human osteochondral allografts: Long-term analysis over 300 days using a Ringer-based solution.

Large osteochondral defects are a major challenge in orthopedics, for which osteochondral allograft (OCA) transplantation is nowadays considered as an option, especially in young patients. However, a major issue with OCA is the need for graft storage, which ensures adequate cartilage integrity over time. The aim of this study was to test how long a Ringer-based storage solution can provide good graft quality after explantation and thus meet the requirements for OCA. For this purpose, human osteochondral allografts of the knee and ankle were analyzed. Live/Dead analysis was performed and glycosaminoglycan, as well as hydroxyproline content, were measured as crucial chondrocyte integrity factors. Furthermore, biomechanical tests focusing on stress relaxation and elastic compression modulus were performed. The critical value of 70% living chondrocytes, which corresponds to a number of 300 cells/mm², was reached after an average of 16 weeks of storage. In addition, a constant cell shrinkage was observed over time. The amount of glycosaminoglycan and hydroxyroline showed a slight and constant decrease over time, but no significant differences when compared from Day 0 to the values at Weeks 40-43. Biomechanical testing also revealed no significant differences at the different time points. Therefore, the results show that the Ringer-based storage solution at 4°C is able to provide a chondrocyte survival of 70% until Week 16. This is comparable to previously published storage solutions. Therefore, the study contributes to the establishment of a Ringer-based osteochondral allograft transplantation system for countries where medium-based storage solution cannot be approved.

Fresh Osteochondral Allograft to Medial Femoral Condyle With Proximal Tibial Opening Wedge Osteotomy

Background: Contributors to knee degeneration include mechanical axis malalignment, patellar maltracking, meniscal deficiency, and tibiofemoral instability. Full-thickness osteochondral defects in young, active patients can lead to significant pain and instability. The gold standard treatment for large (>2 cm2) osteochondral defects is an osteochondral allograft (OCA) which addresses the pathologic articular cartilage loss and underlying bone deficiency. While biologic failure of fresh OCAs is reported, the majority of early failures are attributed to unaddressed mechanical malalignment in the coronal plane. Proximal tibial osteotomy (PTO) corrects malalignment thereby unloading the affected medial compartment and the newly placed OCA, improving long-term survivability. Indications: OCAs are indicated for isolated osteochondral defects and lesions in active young patients. PTO is indicated for patients with varus malalignment who risk potential graft failure of the affected medial compartment. Technique Description: The articular cartilage defect is identified, and a guide pin is drilled in the center. The defect is templated and scored around the margins. A reamer is used to drill to a total depth of 7 to 8 mm. The recipient site is then dilated for graft insertion. On the donor graft, the harvest site is outlined and drilled to the proper diameter. Careful measurement is utilized to ensure graft depth measurements match the recipient site. Once sized, the graft is tapped into place obtaining an anatomic fit along its entire periphery. The osteotomy is performed by using guide pins to delineate the plane cutting the tibia. Fluoroscopy confirmed the osteotomy site and angle. A spacing plate was securely inserted with screws, with placement confirmed by fluoroscopy. Results: Fresh OCAs can restore osteochondral defects. PTO corrects malalignment and unloads the affected medial compartment, decreasing the risk of revision graft failure or total knee arthroplasty. Discussion: Clinical and biomechanical studies that compared isolated and concomitant procedures demonstrated that OCA with PTOs had significantly greater survival rates. Significant malalignment increases the risk of graft failure. It remains unclear whether concomitant osteotomy with osteoarticular allografts leads to increased complication risk; inherent risks remain associated with individual procedures. In adolescents, simultaneous corrective osteotomy along with fresh OCA may delay arthroplasty and associated ambulatory restrictions. Patient Consent Disclosure Statement: The author(s) attests that consent has been obtained from any patient(s) appearing in this publication. If the individual may be identifiable, the author(s) has included a statement of release or other written form of approval from the patient(s) with this submission for publication.

The role of autologous bone grafting in matrix-associated autologous chondrocyte implantation at the knee: Results from the German Cartilage Registry (KnorpelRegister DGOU).

To investigate whether concomitant autologous bone grafting adversely affects clinical outcome and graft survival after matrix-associated autologous chondrocyte implantation (M-ACI). The present study examines registry data of patients who underwent M-ACI with or without autologous bone grafting for large-sized chondral or osteochondral defects. Propensity score matching was performed to exclude potential confounders. A total of 215 patients with similar baseline characteristics were identified. Clinical outcome was assessed at the time of surgery and at 6, 12, 24, 36 and 60 months using the Knee Injury and Osteoarthritis Outcome Score (KOOS). KOOS change, clinical response rate, KOOS subcomponents and failure rate were determined. Patients treated with M-ACI and autologous bone grafting achieved comparable clinical outcomes compared with M-ACI alone. At 24 months postoperatively, the patient-reported outcome (PRO) of patients treated with M-ACI and autologous bone grafting was even significantly better as measured by KOOS (74.9 ± 18.8 vs. 79.2 ± 15.4; p = 0.043). However, the difference did not exceed the minimal clinically important difference (MCID). In patients with M-ACI and autologous bone grafting, a greater change in KOOS relative to baseline was observed at 6 (9.3 ± 14.7 vs. 15.0 ± 14.7; p = 0.004) and 12 months (12.6 ± 17.2 vs. 17.7 ± 14.6; p = 0.035). Overall, a high clinical response rate was observed in both groups at 24 months (75.8% vs. 82.0%; p = n.s.). The estimated survival at the endpoint of reoperation for any reason was 82.1% (SD 2.8) at 8.4 years for isolated M-ACI and 88.7% (SD 2.4) at 8.2 years for M-ACI with autologous bone grafting (p = 0.039). Even in the challenging cohort of large osteochondral defects, the additional treatment with autologous bone grafting leads to remarkably good clinical outcomes in patients treated with M-ACI. In fact, they tend to benefit more from surgery, have lower revision rates and achieve clinical response rates earlier. Subchondral bone management is critical to the success of M-ACI and should be addressed in the treatment of borderline defects. Level III.

Osteochondral Allograft Transplantation in the Knee

Osteochondral injuries of the knee can be a frequent source of debilitating pain and dysfunction. Significant chondral (>1.5-2 cm2) lesions of the femoral condyles can be especially difficult to manage with nonsurgical measures. Fresh osteochondral allograft (OCA) transplantation has been shown to be a reliable surgical procedure to manage a wide array of high-grade focal chondral lesions, with or without subchondral bone involvement. OCA transplantation affords the transfer of a size-matched allograft of mature hyaline cartilage with its associated subchondral bony scaffold. Indications include primary or secondary management of large, high-grade chondral or osteochondral defects secondary to trauma, developmental malformation, osteonecrosis, or other focal degenerative disease. Contraindications include end-stage osteoarthritis, uncorrected malalignment, ligament or meniscus deficiency, and inflammatory joint disease. Improvements in surgical technique, allograft storage, and tissue availability have created more reproducible clinical results and increased chondrocyte viability. Long-term (>10 year) graft survival rates have been shown to be between 70% and 91%, and the procedure has been shown to be cost-effective based on cost per quality-adjusted life year. Finally, OCA transplantation has been shown to provide excellent return to play rate for athletes with medium-to-large cartilage lesions. OCA transplantation is therefore an important option in the treatment algorithm of articular cartilage injuries.

Evaluation of rabbit adipose derived stem cells fate in perfused multilayered silk fibroin composite scaffold for Osteochondral repair.

Development of osteochondral tissue engineering approaches using scaffolds seeded with stem cells in association with mechanical stimulations has been recently considered as a promising technique for the repair of this tissue. In this study, an integrated and biomimetic trilayered silk fibroin (SF) scaffold containing SF nanofibers in each layer was fabricated. The osteogenesis and chondrogenesis of stem cells seeded on the fabricated scaffolds were investigated under a perfusion flow. 3-Dimethylthiazol-2,5-diphenyltetrazolium bromide assay showed that the perfusion flow significantly enhanced cell viability and proliferation. Analysis of gene expression by stem cells revealed that perfusion flow had significantly upregulated the expression of osteogenic and chondrogenic genes in the bone and cartilage layers and downregulated the hypertrophic gene expression in the intermediate layer of the scaffold. In conclusion, applying flow perfusion on the prepared integrated trilayered SF-based scaffold can support osteogenic and chondrogenic differentiation for repairing osteochondral defects.

High quality repair of osteochondral defects in rats using the extracellular matrix of antler stem cells.

Cartilage defects are some of the most common causes of arthritis. Cartilage lesions caused by inflammation, trauma or degenerative disease normally result in osteochondral defects. Previous studies have shown that decellularized extracellular matrix (ECM) derived from autologous, allogenic, or xenogeneic mesenchymal stromal cells (MSCs) can effectively restore osteochondral integrity. To determine whether the decellularized ECM of antler reserve mesenchymal cells (RMCs), a xenogeneic material from antler stem cells, is superior to the currently available treatments for osteochondral defects. We isolated the RMCs from a 60-d-old sika deer antler and cultured them in vitro to 70% confluence; 50 mg/mL L-ascorbic acid was then added to the medium to stimulate ECM deposition. Decellularized sheets of adipocyte-derived MSCs (aMSCs) and antlerogenic periosteal cells (another type of antler stem cells) were used as the controls. Three weeks after ascorbic acid stimulation, the ECM sheets were harvested and applied to the osteochondral defects in rat knee joints. The defects were successfully repaired by applying the ECM-sheets. The highest quality of repair was achieved in the RMC-ECM group both in vitro (including cell attachment and proliferation), and in vivo (including the simultaneous regeneration of well-vascularized subchondral bone and avascular articular hyaline cartilage integrated with surrounding native tissues). Notably, the antler-stem-cell-derived ECM (xenogeneic) performed better than the aMSC-ECM (allogenic), while the ECM of the active antler stem cells was superior to that of the quiescent antler stem cells. Decellularized xenogeneic ECM derived from the antler stem cell, particularly the active form (RMC-ECM), can achieve high quality repair/reconstruction of osteochondral defects, suggesting that selection of decellularized ECM for such repair should be focused more on bioactivity rather than kinship.

Chitosan-Based Hierarchical Scaffolds Crosslinked with Genipin

Osteochondral defects present significant challenges for effective tissue regeneration due to the complex composition of bone and cartilage. To address this challenge, this study presents the fabrication of hierarchical scaffolds combining chitosan/β-tricalcium phosphate (β-TCP) to simulate a bone-like layer, interconnected with a silk fibroin layer to mimic cartilage, thus replicating the cartilage-like layer to mimic the native osteochondral tissue architecture. The scaffolds were produced by freeze-drying and then crosslinking with genipin. They have a crosslinking degree of up to 24%, which promotes a structural rearrangement and improved connection between the different layers. Micro-CT analysis demonstrated that the structures have distinct porosity values on their top layer (up to 84%), interface (up to 65%), and bottom layer (up to 77%) and are dependent on the concentration of β-tricalcium phosphate used. Both layers were confirmed to be clearly defined by the distribution of the components throughout the constructs, showing adequate mechanical properties for biomedical use. The scaffolds exhibited lower weight loss (up to 7%, 15 days) after enzymatic degradation due to the combined effects of genipin crosslinking and β-TCP incorporation. In vitro studies showed that the constructs supported ATDC5 chondrocyte-like cells and MC3T3 osteoblast-like cells in duo culture conditions, providing a suitable environment for cell adhesion and proliferation for up to 14 days. Overall, the physicochemical properties and biological results of the developed chitosan/β-tricalcium phosphate/silk fibroin bilayered scaffolds suggest that they may be potential candidates for osteochondral tissue strategies.

3D Printing of Cobalt-Incorporated Chloroapatite Bioceramic Composite Scaffolds with Antioxidative Activity for Enhanced Osteochondral Regeneration.

Osteochondral defects are often accompanied by excessive reactive oxygen species (ROS) caused by osteoarthritis or acute surgical inflammation. An inflammatory environment containing excess ROS will not only hinder tissue regeneration but also impact the quality of newly formed tissues. Therefore, there is an urgent need to develop scaffolds with both ROS scavenging and osteochondral repair functions to promote and protect osteochondral tissue regeneration. In this work, by using 3D printing technology, a composite scaffold based on cobalt-incorporated chloroapatite (Co-ClAP) bioceramics, which possesses ROS-scavenging activity and can support cell proliferation, adhesion, and differentiation, is developed. Benefiting from the catalytic activity of Co-ClAP bioceramics, the composite scaffold can protect cells from oxidative damage under ROS-excessive conditions, support their directional differentiation, and simultaneously mediate an anti-inflammatory microenvironment. In addition, it is also confirmed by using rabbit osteochondral defect model that the Co-ClAP/poly(lactic-co-glycolic acid) scaffold can effectively promote the integrated regeneration of cartilage and subchondral bone, exhibiting an ideal repair effect in vivo. This study provides a promising strategy for the treatment of defects with excess ROS and inflammatory microenvironments.

Surgical treatment of chondral defects of the knee joint and
 a new look at the role and position of mosaic autochondroplasty

The article presents an analytical review of currently used methods of organ-preserving surgical treatment of chondral defects of the knee joint from the standpoint of their pathogenetic orientation. The systematization and comparative characteristics of the methods of joint-preserving surgical treatment of patients of this category are presented with a critical analysis of various types of operations used for full-thickness and penetrating hyaline cartilage defects. One of the main methods of surgical treatment of defects of III and IV degrees (according to the classification ICRS) mosaic chondroplasty is considered in detail. An analytical assessment of the indications, contraindications and conditions for performing mosaic autoplasty of the articular surfaces of the knee joint is given in the aspect of historical retrospective and the results of current research. The debatable provisions and problems of using the classical version of mosaic chondroplasty in its application in the case of destructive-dystrophic genesis of osteochondral defect are formulated. Dogmatic attitudes regarding mosaic chondroplasty, which require critical revision in relation to themselves, have been submitted for discussion. The authors present and describe in detail the developed new methods of mosaic chondroplasty, based on the current understanding of the pathogenesis of osteoarthritis and osteonecrosis of the knee joint, as well as the role of the subchondral bone in the development of both these diseases and associated articular cartilage defects. The surgical instruments developed by the authors for the implementation of new methods of chondroplasty are described.
 The authors conclude that there is an urgent need to develop the concept of organ-preserving surgery for destructive-dystrophic joint lesions, which should be based on data on the significance of subchondral and metaphyseal bone tissue in the above pathological processes and the unconditional need for their correction during surgical reconstruction.

3D bio scaffold support osteogenic differentiation of mesenchymal stem cells.

The regeneration of osteochondral lesions by tissue engineering techniques is challenging due to the lack of physicochemical characteristics and dual-lineage (osteogenesis and chondrogenesis). A scaffold with better mechanical properties and dual lineage capability is required for the regeneration of osteochondral defects. In this study, a hydrogel prepared from decellularized human umbilical cord tissue was developed and evaluated for osteochondral regeneration. Mesenchymal stem cells (MSCs) isolated from the umbilical cord were seeded with hydrogel for 28 days, and cell-hydrogel composites were cultured in basal and osteogenic media. Alizarin red staining, quantitative polymerase chain reaction, and immunofluorescent staining were used to confirm that the hydrogel was biocompatible and capable of inducing osteogenic differentiation in umbilical cord-derived MSCs. The findings demonstrate that human MSCs differentiated into an osteogenic lineage following 28 days of cultivation in basal and osteoinductive media. The expression was higher in the cell-hydrogel composites cultured in osteoinductive media, as evidenced by increased levels of messenger RNA and protein expression of osteogenic markers as compared to basal media cultured cell-hydrogel composites. Additionally, calcium deposits were also observed, which provide additional evidence of osteogenic differentiation. The findings demonstrate that the hydrogel is biocompatible with MSCs and possesses osteoinductive capability in vitro. It may be potentially useful for osteochondral regeneration.

Subchondral Bone Alignment in Osteochondral Allograft Transplants for Large Oval Defects of the Medial Femoral Condyle: Comparison of Lateral versus Medial Femoral Condyle Donors.

Supply-demand mismatch of medial femoral condyle (MFC) osteochondral allografts (OCAs) remains a rate-limiting factor in the treatment of osteochondral defects of the femoral condyle. Surface contour mapping was used to determine whether a contralateral lateral femoral condyle (LFC) versus ipsilateral MFC OCA differs in the alignment of donor:native subchondral bone for large osteochondral defects of the MFC. Thirty fresh-frozen human femoral condyles were matched by tibial width into 10 groups of 3 condyles (MFC recipient, MFC donor, and LFC donor) each for 3 cartilage surgeons (90 condyles). The recipient MFC was imaged using nano-computed tomography scan. Donor oval grafts were harvested from each matched condyle and transplanted into a 17 mm × 36 mm defect created in the recipient condyle. Following the first transplant, the recipient condyle was imaged and superimposed on the native condyle nano-CT scan. The donor plug was removed and the process repeated for the other donor. Surface height deviation and circumferential step-off height deviation were compared between native and donor subchondral bone surfaces for each transplant. There was no statistically significant difference in mean subchondral bone surface deviation (LFC = 0.87 mm, MFC = 0.76 mm, P = 0.07) nor circumferential step-off height (LFC = 0.93 mm, MFC = 0.85 mm, P = 0.09) between the LFC and MFC plugs. There were no significant differences in outcomes between surgeons. There were no significant differences in subchondral bone circumferential step-off or surface deviation between ipsilateral MFC and contralateral LFC oval-shaped OCAs for 17 mm × 36 mm defects of the MFC.

Protecting the regenerative environment: selecting the optimal delivery vehicle for cartilage repair—a narrative review

Focal cartilage defects are common in youth and older adults, cause significant morbidity and constitute a major risk factor for developing osteoarthritis (OA). OA is the most common musculoskeletal (MSK) disease worldwide, resulting in pain, stiffness, loss of function, and is currently irreversible. Research into the optimal regenerative approach and methods in the setting of either focal cartilage defects and/or OA holds to the ideal of resolving both diseases. The two fundamentals required for cartilage regenerative treatment are 1) the biological element contributing to the regeneration (e.g., direct application of stem cells, or of an exogenous secretome), and 2) the vehicle by which the biological element is suspended and delivered. The vehicle provides support to the regenerative process by providing a protective environment, a structure that allows cell adherence and migration, and a source of growth and regenerative factors that can activate and sustain regeneration. Models of cartilage diseases include osteochondral defect (OCD) (which usually involve one focal lesion), or OA (which involves a more diffuse articular cartilage loss). Given the differing nature of these models, the optimal regenerative strategy to treat different cartilage diseases may not be universal. This could potentially impact the translatability of a successful approach in one condition to that of the other. An analogy would be the repair of a pothole (OCD) versus repaving the entire road (OA). In this narrative review, we explore the existing literature evaluating cartilage regeneration approaches for OCD and OA in animal then in human studies and the vehicles used for each of these two conditions. We then highlight strengths and challenges faced by the different approaches presented and discuss what might constitute the optimal cartilage regenerative delivery vehicle for clinical cartilage regeneration.

The Phenotype of Mesenchymal Stromal Cell and Articular Chondrocyte Cocultures on Highly Porous Bilayer Poly-L-Lactic Acid Scaffolds Produced by Thermally Induced Phase Separation and Supplemented with Hydroxyapatite.

Bilayer scaffolds could provide a suitable topology for osteochondral defect repair mimicking cartilage and subchondral bone architecture. Hence, they could facilitate the chondro- and osteogenic lineage commitment of multipotent mesenchymal stromal cells (MSCs) with hydroxyapatite, the major inorganic component of bone, stimulating osteogenesis. Highly porous poly-L-lactic acid (PLLA) scaffolds with two layers of different pore sizes (100 and 250 µm) and hydroxyapatite (HA) supplementation were established by thermally induced phase separation (TIPS) to study growth and osteogenesis of human (h) MSCs. The topology of the scaffold prepared via TIPS was characterized using scanning electron microscopy (SEM), a microCT scan, pycnometry and gravimetric analysis. HMSCs and porcine articular chondrocytes (pACs) were seeded on the PLLA scaffolds without/with 5% HA for 1 and 7 days, and the cell attachment, survival, morphology, proliferation and gene expression of cartilage- and bone-related markers as well as sulfated glycosaminoglycan (sGAG) synthesis were monitored. All scaffold variants were cytocompatible, and hMSCs survived for the whole culture period. Cross-sections revealed living cells that also colonized inner scaffold areas, producing an extracellular matrix (ECM) containing sGAGs. The gene expression of cartilage and bone markers could be detected. HA represents a cytocompatible supplement in PLLA composite scaffolds intended for osteochondral defects.

A 3D printed biomimetic scaffold for cartilage regeneration with lubrication, load-bearing, and adhesive fixation properties

Reconstructing the tri-layer structure of articular cartilage (AC) and replicating its functions pose significant challenges. In response, we propose a novel approach utilizing 3D printing technology to replicate and reconstruct the complex structure of AC. This is achieved by introducing three distinct functional hydrogels, each providing lubrication, load-bearing, and adhesive fixation functions. We have systematically characterized the structure, chemical composition, and function of each layer. The results demonstrate the effectiveness of the tri-layer scaffold, which exhibits low friction, mechanical properties similar to natural AC, excellent adhesion capacity, and good biocompatibility. This study paves the way for innovation in the traditional methods of preparing biomimetic AC and has broad applications in osteochondral (OC) defect repair.

Treatment of osteochondral injuries of the humeral head using fresh osteochondral allograft transplantation

BackgroundLarge osteochondral lesions of the humeral head can result from locked posterior dislocations, avascular necrosis, and osteochondritis dissecans. Fresh osteochondral allograft (OCA) transplantation is a treatment option for young patients with focal osteochondral defects of the humeral head. The purpose of this case series was to assess graft survivorship, subjective patient-reported outcomes (PROMs), and satisfaction among seven patients who underwent OCA transplantation of the humeral head. MethodsWe identified seven patients who underwent humeral head OCA transplantation between 2008 and 2017. A custom questionnaire for patient reported outcome measures including ASES, QuickDASH, Likert satisfaction, and reoperations was mailed to each patient. Clinical failure was defined as further surgery that involved removal of the allograft. ResultsMedian follow-up duration was 10 years (range, 4.6 to 13.5 years) with a median age of 21.6 years (range, 18.5 to 43.5 years). Most patients (86%) reported improved function and reduced pain. At final follow-up, 71% of patients reported ongoing problems with their shoulder including pain, stiffness, clicking/grinding, limited range of motion, and instability. Return to recreational activities was high at 86% but 43% expressed limitations with activity due to their shoulder. Overall satisfaction was high at 71% with mean ASES and QuickDASH scores at 62.4 and 29.2 respectively. Reoperation after OCA occurred in one patient (14%). ConclusionsAmong this case series of seven patients who underwent OCA transplantation of the humeral head, patient satisfaction was high at 10 year follow-up and most returned to recreational activity although most also had persistent shoulder symptoms.

PUD@HA/PEEK Scaffold Induces Subchondral Bone Regeneration to Repair Osteochondral Defect in Rabbits.

Osteochondral defects (OCDs) pose a significant challenge in clinical practice, and recent advancements in their repair indicate that satisfying subchondral bone repair may be critical for this. Herein, a series of hydroxyapatite/poly(ether ether ketone) (HA/PEEK) scaffolds were fabricated with varying mass percentages (0, 20, 30, and 40%) to induce subchondral bone regeneration. Subsequently, an optimal scaffold with 40% HA/PEEK was selected to establish osteochondral scaffolds with poly(ether urethane) urea-Danshensu (PUD) for repairing the OCD. The material characteristics of HA/PEEK and PUD were investigated using scanning electron microscopy, tensile, swelling, and fatigue tests, and cytological experiments. The effects of serial HA/PEEK scaffolds on subchondral bone repair were then assessed by using microcomputed tomography, hard tissue slicing, and histological staining. Furthermore, the optimal 40% HA/PEEK scaffold was used to develop osteochondral scaffolds with PUD to observe the effect on the OCD repair. HA/PEEK materials exhibited an even HA distribution in PEEK. However, when composited with HA, PEEK exhibited inferior mechanical strength. 40%HA/PEEK scaffolds showed an optimum effect on in vivo subchondral bone repair. Cartilage regeneration on 40%HA/PEEK scaffolds was pronounced. After PUD was introduced onto the HA/PEEK, the PUD@40%HA/PEEK scaffold produced the expected effect on the repair of the OCD in rabbits. Therefore, achieving satisfactory subchondral bone repair can benefit surficial cartilage repair. The PUD@40%HA/PEEK scaffold could induce subchondral bone regeneration to repair the OCD in rabbits and could provide a novel approach for the repair of the OCD in clinical practice.

Incorporating strontium enriched amorphous calcium phosphate granules in collagen/collagen-magnesium-hydroxyapatite osteochondral scaffolds improves subchondral bone repair

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

Comparison of the ability of exosomes and ectosomes derived from adipose-derived stromal cells to promote cartilage regeneration in a rat osteochondral defect model

BackgroundExtracellular vesicles (EVs) derived from mesenchymal stromal cells (MSCs) offer promising prospects for stimulating cartilage regeneration. The different formation mechanisms suggest that exosomes and ectosomes possess different biological functions. However, little attention has been paid to the differential effects of EV subsets on cartilage regeneration.MethodsOur study compared the effects of the two EVs isolated from adipose-derived MSCs (ASCs) on chondrocytes and bone marrow–derived MSCs (BMSCs) in vitro. Additionally, we loaded the two EVs into type I collagen hydrogels to optimize their application for the treatment of osteochondral defects in vivo.ResultsIn vitro experiments demonstrate that ASC-derived exosomes (ASC-Exos) significantly promoted the proliferation and migration of both cells more effectively than ASC-derived ectosomes (ASC-Ectos). Furthermore, ASC-Exos facilitated a stronger differentiation of BMSCs into chondrogenic cells than ASC-Ectos, but both inhibited chondrocyte apoptosis to a similar extent. In the osteochondral defect model of rats, ASC-Exos promoted cartilage regeneration in situ better than ASC-Ectos. At 8 weeks, the hydrogel containing exosomes group (Gel + Exo group) had higher macroscopic and histological scores, a higher value of trabecular bone volume fraction (BV/TV), a lower value of trabecular thickness (Tb.Sp), and a better remodeling of extracellular matrix than the hydrogel containing ectosomes group (Gel + Ecto group). At 4 and 8 weeks, the expression of CD206 and Arginase-1 in the Gel + Exo group was significantly higher than that in the Gel + Ecto group.ConclusionOur findings indicate that administering ASC-Exos may be a more effective EV strategy for cartilage regeneration than the administration of ASC-Ectos.