In-Vivo Efficacy of Compliant 3D Nano-Composite in Critical-Size Bone Defect Repair: a Six Month Preclinical Study in Rabbit

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.

Characterization and In Vitro evaluation of a novel coated nanocomposite porous 3D scaffold for bone repair

“…This flaw phenomenon is frequently appearing in polymer-based scaffold and coated framework, as developed in this study. Many studies have reported the enhancement of mechanical characteristics of scaffolds by integration of inorganic biological substances (44)(45)(46). Gelatin, dextrin and dextran are known natural polymers that form a fragile hydrogel like scaffolds.…”

Ovariectomized Rats with Established Osteopenia have Diminished Mesenchymal Stem Cells in the Bone Marrow and Impaired Homing, Osteoinduction and Bone Regeneration at the Fracture Site

“…Microarchitectural parameters including, bone volume fraction (BV/TV), trabecular thickness (Tb.Th), trabecular separation (Tb.Sp), trabecular number (Tb.N) and structure model index (SMI) were quantified as described before [33,34] Loading of MSC with 3D Scaffold at Fractured Site To study the therapeutic effect of cont MSC and Ovx MSC in equal number with 3D scaffold at fractured site in female rats was evaluated. A 3-D nano-hydroxyapatite/gelatin/ carboxymethyl chitin (n-HA/gel/CMC) scaffold constructs were prepared by solvent casting method combined with glutaraldehyde vapour crosslinking and freeze drying method as described before [35,36]. The scaffolds were removed from the sterile patches and wetted with blood that oozed out from the incision during surgery.…”

Fabrication of Novel Hydrogel with Berberine-Enriched Carboxymethylcellulose and Hyaluronic Acid as an Anti-Inflammatory Barrier Membrane

“…CMC is a polysaccharide based hydrogel that when incorporated with hydroxyapatite in a CMC-based hydrogel provides excellent tissue engineering function [14]. In 2013, Sagar et al developed a nanohydroxyapatite/gelatin and chemically carboxymethylated chitin scaffold that enhanced osteoblastic activity and mineralization [15]. However, cellulose-based hydrogels lack good mechanical proprieties for clinical use [14].…”