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

Abstract

BackgroundThe 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/purposeThe hypothesis was that the implantation of the Ar-HA implant leads to tissue regeneration and maturation.Study designA 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).MethodsCritical 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.ResultsIn 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.ConclusionAr-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 relevanceOsteochondral 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.

Therapeutic Potential of Articular Cartilage Regeneration using Tissue Engineering Based on Multiphase Designs

“…The Agili-C™ CartiHeal is a biphasic scaffold, which consists in of a cartilage phase made of hyaluronic acid and a bone layer comprised by crystalline aragonite (calcium carbonate based). After in vivo trial (goat model), this acellular scaffolds evidenced the potential to recruit cells from the host tissues, and enhanced hyaline cartilage formation and subchondral bone regeneration with Therapeutic Potential of Articular Cartilage Regeneration using Tissue Engineering Based… DOI: http://dx.doi.org/10.5772/intechopen.84697 a continuous maturation process without deterioration of the repair tissue after 12 months implanted in critical osteochondral defects [111]. For clinical trials, only one clinical case has been reported in a 47-year-old man with an injury Outerbridge grade IV.…”

“…Biphasic acellular scaffold with a cartilage phase consisting of hyaluronic acid attached to a bone phase consisting of aragonite Scaffold has an interconnecting porosity, with an average of 100-μm pore size, able to support human stem cell adhesion Using a goat model of a critical osteochondral defect, the formation of hyaline cartilage and subchondral bone regeneration in the area of the lesion is demonstrated [111] The scaffold was used on an Outerbridge grade IV promoting the mesenchymal stem-cell migration, and after 24 months, the articular surface appeared restored by MRI (Agili-C™ ) [112] [ 111,112] Acellular scaffold made from polylactidecoglycolide copolymer and a bone phase containing calcium sulfate A porous and resorbable scaffold with an osteoinductive environment due to the added calcium sulfate. The polyglycolic acid fibers, which are arranged in an orderly manner, give the structure a mechanical reinforcement [113] Using a goat model of a critical osteochondral defect, a good filling of osteochondral defects, suitable integration with the native cartilage, and a high percentage of hyaline-like cartilage were demonstrated [114] Reports in the literature about TruFit™ are controversial.…”

Current and novel injectable hydrogels to treat focal chondral lesions: Properties and applicability

“…Most of these studies suggest promising results with improved cartilage regeneration between 3 months and 2 years. 26,[32][33][34][35][36] Significant superior histologic evidence of cartilage regeneration when using hydrogels are reported when compared to empty defects. The cell sources, collection techniques, cell processing, qualitative and quantitative characterizations, and delivery methods vary widely between studies.…”

Concise Review: Biomimetic Functionalization of Biomaterials to Stimulate the Endogenous Healing Process of Cartilage and Bone Tissue

“…Although the work has not been applied to an osteoarthritic model, there are high hopes that this device could be useful to decrease the inflammatory environment of osteoarthritis and ameliorate cartilage regeneration. If we widen our scope to find more relevant clinical studies, biphasic osteochondral scaffolds allow for the fabrication of bigger scaffolds, facilitating the fixation of the material, thus having success at the implantation in vivo [99]. However, the ultimate goal is to achieve early repair of the cartilage tissue to stop the development of osteoarthritis and any damage that also occurs to the subchondral bone [71].…”