Abstract

Several biomaterials have recently been developed to address the challenge of osteochondral regeneration. Among these, chitosan holds promises both for cartilage and bone healing. The aim of this in vivo study was to evaluate the regeneration potential of a novel hybrid magnesium-doped hydroxyapatite (MgHA), collagen, chitosan-based scaffold, which was tested in a sheep model to ascertain its osteochondral regenerative potential, and in a rabbit model to further evaluate its ability to regenerate bone tissue. Macroscopic, microtomography, histology, histomorphometry, and immunohistochemical analysis were performed. In the sheep model, all analyses did not show significant differences compared to untreated defects (p > 0.05), with no evidence of cartilage and subchondral bone regeneration. In the rabbit model, this bone scaffold provided less ability to enhance tissue healing compared with a commercial bone scaffold. Moreover, persistence of scaffold material and absence of integration with connective tissue around the scaffolds were observed. These results raised some concerns about the osteochondral use of this chitosan composite scaffold, especially for the bone layer. Further studies are needed to explore the best formulation of chitosan-reinforced composites for osteochondral treatment.

Highlights

  • Chondral and osteochondral defects are challenging problems, since the native structure of cartilage and subchondral bone cannot be regenerated with any of the available treatments [1,2]

  • Due to the key role of subchondral bone for the success of osteochondral treatment, a rabbit model was used to evaluate bone isolated from the articular environment, and its contribution toward the overall osteochondral regeneration induced by this chitosan-reinforced scaffold

  • The main finding of this study is that the hybrid magnesium-doped hydroxyapatite (MgHA)–collagen–chitosan scaffolds failed to provide both bone and cartilage regeneration in vivo

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Summary

Introduction

Chondral and osteochondral defects are challenging problems, since the native structure of cartilage and subchondral bone cannot be regenerated with any of the available treatments [1,2]. Subchondral bone is currently emerging as the main challenge for the achievement of optimal osteochondral regeneration [13,14]. Even though these findings did not correlate with worse clinical outcomes, and despite a slow but significant improvement of regenerating tissue scores, this aspect underlines the limits of this biomaterial potential to restore damaged articular tissue, at cartilage but even more at bone level. In the present study a hybrid osteochondral cell-free scaffold, obtained by a blending process, to achieve a collagen and chitosan (col+chit)-reinforced blend, and by a bio-inspired mineralization process, to grow MgHA nanoparticles on col+chit blends (MgHA/(col+chit)), was developed and tested in vivo. Due to the key role of subchondral bone for the success of osteochondral treatment, a rabbit model was used to evaluate bone isolated from the articular environment, and its contribution toward the overall osteochondral regeneration induced by this chitosan-reinforced scaffold

Post-Implant and Macroscopic Evaluations
Microtomography
Histology and Histomorphometry
Immunohistochemistry
Discussion
Bone Scaffold Preparation
Cartilaginous Layer Scaffold Preparation
Osteochondral Scaffold Preparation
Surgical Procedures
Rabbit Model
Sheep Model
Morphological Parameters
Immunohistochemical Analysis
Statistical Analysis
Conclusions
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