Reconstruction of Large Osteochondral Defects Using a Hemicondylar Aragonite-Based Implant in a Caprine Model.

PURPOSE: To investigate the safety and regenerative potential of a hemicondylar aragonite-based scaffold in the reconstruction of large osteochondral lesions occupying an extensive portion of the medial femoral condyle in a goat model. METHODS: Eight Saanen goats were treated by the implantation of an aragonite-based scaffold (size: 19 × 8 × 8 mm) on a previously prepared hemicondylar osteochondral defect located in the right medial femoral condyle of the knee. Goats were euthanized after 12 months and the specimens underwent X-ray imaging, macroscopic, micro-computed tomography, histology, and immunohistochemistry evaluations to assess subchondral bone and cartilage regeneration. RESULTS: In all 8 goats, no adverse event or persistent inflammation was observed. The evaluations performed showed integration of the scaffold, which almost completely resorbed at 12 months. In all animals, no signs of osteoarthritis progression were seen. Concurrent regeneration of the osteochondral unit was observed, with trabecular bone tissue replacing the implant and restoring the subchondral layer, and the formation of an overlying hyaline cartilage surface, well integrated within the surrounding native tissue, also was observed. CONCLUSIONS: The use of the hemicondylar biphasic aragonite-based implant in the treatment of osteochondral defects in the goat model proved to be technically feasible and safe. The scaffold degraded and was replaced by regenerated tissue within the 12-month study period, restoring the osteochondral unit both at the level of the cartilaginous layer and the subchondral bone. CLINICAL RELEVANCE: The present animal study describes a scaffold-based procedure for the treatment of large condylar defects, which often require massive allograft or unicompartmental replacement. The aragonite-based implant promoted a regeneration of both cartilage and subchondral bone, and its use as a "biologic" unicondylar prosthesis might be feasible also in the clinical setting.

Chondroprotective effects of a polycarbonate-urethane meniscal implant: histopathological results in a sheep model.

PURPOSE: injury or loss of the meniscus generally leads to degenerative osteoarthritic changes in the knee joint. However, few surgical options exist for meniscal replacement. The goal of this study was to examine the ability of a non-degradable, anatomically shaped artificial meniscal implant, composed of Kevlar-reinforced polycarbonate-urethane (PCU), to prevent progressive cartilage degeneration following complete meniscectomy. METHODS: the artificial meniscus was implanted in the knees of mature female sheep following total medial meniscectomy, and the animals were killed at 3- and 6-months post-surgery. Macroscopic analysis and semi-quantitative histological analysis were performed on the cartilage of the operated knee and unoperated contralateral control joint. RESULTS: the PCU implants remained well secured throughout the experimental period and showed no signs of wear or changes in structural or material properties. Histological analysis showed relatively mild cartilage degeneration that was dominated by loss of proteoglycan content and cartilage structure. However, the total osteoarthritis score did not significantly differ between the control and operated knees, and there were no differences in the severity of degenerative changes between 3 and 6 months post-surgery. CONCLUSION: current findings provide preliminary evidence for the ability of an artificial PCU meniscal implant to delay or prevent osteoarthritic changes in knee joint following complete medial meniscectomy.

Bone Regeneration in Load-Bearing Segmental Defects, Guided by Biomorphic, Hierarchically Structured Apatitic Scaffold.

The regeneration of load-bearing segmental bone defects remains a significant clinical problem in orthopedics, mainly due to the lack of scaffolds with composition and 3D porous structure effective in guiding and sustaining new bone formation and vascularization in large bone defects. In the present study, biomorphic calcium phosphate bone scaffolds (GreenBone™) featuring osteon-mimicking, hierarchically organized, 3D porous structure and lamellar nano-architecture were implanted in a critical cortical defect in sheep and compared with allograft. Two different types of scaffolds were tested: one made of ion-doped hydroxyapatite/ß-tricalcium-phosphate (GB-1) and other made of undoped hydroxyapatite only (GB-2). X-ray diffraction patterns of GB-1 and GB-2 confirmed that both scaffolds were made of hydroxyapatite, with a minor amount of ß-TCP in GB-1. The chemical composition analysis, obtained by ICP-OES spectrometer, highlighted the carbonation extent and the presence of small amounts of Mg and Sr as doping ions in GB-1. SEM micrographs showed the channel-like wide open porosity of the biomorphic scaffolds and the typical architecture of internal channel walls, characterized by a cell structure mimicking the natural parenchyma of the rattan wood used as a template for the scaffold fabrication. Both GB-1 and GB-2 scaffolds show very similar porosity extent and 3D organization, as also revealed by mercury intrusion porosimetry. Comparing the two scaffolds, GB-1 showed slightly higher fracture strength, as well as improved stability at the stress plateau. In comparison to allograft, at the follow-up time of 6 months, both GB-1 and GB-2 scaffolds showed higher new bone formation and quality of regenerated bone (trabecular thickness, number, and separation). In addition, higher osteoid surface (OS/BS), osteoid thickness (OS.Th), osteoblast surface (Ob.S/BS), vessels/microvessels numbers, as well as substantial osteoclast-mediated implant resorption were observed. The highest values in OS.Th and Ob. S/BS parameters were found in GB-1 scaffold. Finally, Bone Mineralization Index of new bone within scaffolds, as determined by micro-indentation, showed a significantly higher microhardness for GB-1 scaffold in comparison to GB-2. These findings suggested that the biomorphic calcium phosphate scaffolds were able to promote regeneration of load-bearing segmental bone defects in a clinically relevant scenario, which still represents one of the greatest challenges in orthopedics nowadays.

Osteochondral regeneration with a novel aragonite-hyaluronate biphasic scaffold: up to 12-month follow-up study in a goat model.

BACKGROUND: The regeneration of articular hyaline cartilage remains an elusive goal despite years of research. Recently, an aragonite-hyaluronate (Ar-HA) biphasic scaffold has been described capable of cartilage regeneration over a 6-month follow-up period. This study was conducted in order to assess the fate of the regenerated osteochondral tissue in a 12-month-long validated caprine model. HYPOTHESIS/PURPOSE: The hypothesis was that the implantation of the Ar-HA implant leads to tissue regeneration and maturation. STUDY DESIGN: A two-arm caprine model of a critical osteochondral defect compares the fate of acute osteochondral defects (group A) to Ar-HA implanted defects (group B). METHODS: Critical 6 mm in diameter and 10-mm in depth osteochondral defects were created in the load-bearing medial femoral condyle of 20 mature goats and randomized into two groups. In group A (n = 6), a blood clot spontaneously filled the defect; in group B (n = 14), a single Ar-HA implant reconstructed the defect. The animals were sacrificed after either 6 or 12 months. Parameters assessed included clinical evaluation, x-rays, micro-CT, ultrasound and histology at both time points, and specimen high-field magnetic resonance imaging with T2 mapping at the 12-month time point. RESULTS: In most group A animals, the defects were not reconstructed (1/3 at 6 months, and 0/3 at 12 months). Defects in group B were mostly reconstructed (5/7 at 6 months and 6/7 at 12 months). Group A defects were either empty or contained fibrous repair tissue; while group B filling was compatible with hyaline cartilage and normal bone. CONCLUSION: Ar-HA scaffolds implanted in critical osteochondral defects result in hyaline cartilage formation and subchondral bone regeneration. The results improved at the 12-month time point compared to the 6-month time point, indicating a continuous maturation process without deterioration of the repair tissue. CLINICAL RELEVANCE: Osteochondral defects are common in humans; the results of the current study suggest that an acellular Ar-HA scaffold might induce cartilage and subchondral bone regeneration.