title: 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.
authors.affiliation: Department of Biosciences and Bioengineering, Indian Institute of Technology-Bombay, Mumbai, Maharashtra, India.
authors.forename: Nitin
authors.initials: N
authors.lastname: Sagar
authors.forename: Alok K
authors.initials: AK
authors.lastname: Pandey
authors.forename: Deepak
authors.initials: D
authors.lastname: Gurbani
authors.forename: Kainat
authors.initials: K
authors.lastname: Khan
authors.forename: Dhirendra
authors.initials: D
authors.lastname: Singh
authors.forename: Bhushan P
authors.initials: BP
authors.lastname: Chaudhari
authors.forename: Vivek P
authors.initials: VP
authors.lastname: Soni
authors.forename: Naibedya
authors.initials: N
authors.lastname: Chattopadhyay
authors.forename: Alok
authors.initials: A
authors.lastname: Dhawan
authors.forename: Jayesh R
authors.initials: JR
authors.lastname: Bellare
mesh_terms: D000818:Animals; D001861:Bone Regeneration / Q000502:physiology*; D018786:Bone Substitutes / Q000627:therapeutic use*; D017886:Durapatite / Q000627:therapeutic use; D005780:Gelatin / Q000627:therapeutic use; D008297:Male; D053761:Nanocomposites / Q000627:therapeutic use*; D016062:Porosity; D011817:Rabbits; D019651:Plastic Surgery Procedures / Q000379:methods; D013977:Tibia / Q000502:physiology*; D023822:Tissue Engineering / Q000379:methods; D054457:Tissue Scaffolds; D014945:Wound Healing / Q000502:physiology*
chemical_list: D018786:Bone Substitutes; D005780:Gelatin; D017886:Durapatite