Abstract

Bone defects above critical size do not heal completely by itself and thus represent major clinical challenge to reconstructive surgery. Numerous bone substitutes have already been used to promote bone regeneration, however their use, particularly for critical-sized bone defects along with their long term in vivo safety and efficacy remains a concern. The present study was designed to obtain a complete healing of critical-size defect made in the proximal tibia of New Zealand White rabbit, using nano-hydroxyapatite/gelatin and chemically carboxymethylated chitin (n-HA/gel/CMC) scaffold construct. The bone-implant interfaces and defect site healing was evaluated for a period up to 25 weeks using radiography, micro-computed tomography, fluorescence labeling, and histology and compared with respective SHAM (empty contra lateral control). The viscoelastic porous scaffold construct allows easy surgical insertion and post-operatively facilitate oxygenation and angiogenesis. Radiography of defect treated with scaffold construct suggested expedited healing at defect edges and within the defect site, unlike confined healing at edges of the SHAM sites. The architecture indices analyzed by micro-computed tomography showed a significant increase in percentage of bone volume fraction, resulted in reconciled cortico-trabecular bone formation at n-HA/gel/CMC constructs treated site (15.2% to 52.7%) when compared with respective SHAM (10.2% to 31.8%). Histological examination and fluorescence labeling revealed that the uniformly interconnected porous surface of scaffold construct enhanced osteoblasts’ activity and mineralization. These preclinical data suggest that, n-HA/gel/CMC construct exhibit stimulation of bone's innate regenerative capacity, thus underscoring their use in guided bone regeneration.

Highlights

  • New and innovative processes are being evolved to promote and facilitate bone regeneration

  • The hybrid materials with controlled and tailorable properties due to favourable ionic interactions between the inorganic and organic constituents could be designed for diverse application in both hard and soft tissue regeneration [29,30]. It would be more effective; if along with the above tailorable hybrid properties the material is carvable and/or amenable to contouring for optimal adaptation to the various shapes of bone defects without failure and or fracture [31,32,33]. We have developed such biomaterial as a self-organized n-HA/gel/carboxymethyl chitin (CMC) scaffold construct and have been successfully tested concerning its physicochemical, morphological, mechanical, hemocompatible and biocompatible properties to prove the influence of acidic derivative of natural polymer used in functionalization of the composite material [34]

  • We test the in vivo feasibility of the n-HA/gel/CMC scaffold construct to act as a process-directing agent to promote mineralized tissue formation for the treatment of bone defects

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Summary

Introduction

New and innovative processes are being evolved to promote and facilitate bone regeneration. It would be more effective; if along with the above tailorable hybrid properties the material is carvable and/or amenable to contouring for optimal adaptation to the various shapes of bone defects without failure and or fracture [31,32,33] We have developed such biomaterial as a self-organized n-HA/gel/CMC scaffold construct and have been successfully tested concerning its physicochemical, morphological, mechanical, hemocompatible and biocompatible properties to prove the influence of acidic derivative of natural polymer used in functionalization (due to presence of both carboxyl and amino groups) of the composite material [34]. We test the in vivo feasibility of the n-HA/gel/CMC scaffold construct to act as a process-directing agent to promote mineralized tissue formation for the treatment of bone defects

Methods
Results
Conclusion

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