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Queen Mary University of LondonQueen Mary University of London
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School of Engineering and Materials Science
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PhD Thesis: Osteoinduction by biomaterials; towards unravelling the underlying process

Author: SIVASUBRAMANYAM, Kruba Sankar

Year: 2011

Supervisor(s): Joost de Bruijn

Osteoinduction is seen as bone formation induced in ectopic sites such as muscle or subcutaneous tissue where bone is not normally found. Bone is induced in ectopic sites by a number of biomaterials with specific structural and chemical features. This process involves recruitment of progenitor cells to the material surface, their osteogenic differentiation and ultimately formation of bone. However the mechanism of bone induction by synthetic biomaterials is not known. The aim of this thesis is to contribute towards understanding the mechanism of osteoinduction by biomaterials. Experiments conducted based on a hypothesis that the surface microtopography of osteoinductive biomaterials stimulates inflammatory macrophages to secrete bone inducing factors that recruit and stimulate progenitor cells to osteoblasts. In vitro experiments indicate osteoinductive materials stimulate macrophages to secrete prostaglandin E2 (PGE2) which recruits and differentiates progenitor cells to osteoblast. In vivo experiments conducted in canines to investigate the role of prostaglandins in osteoinduction was unsuccessful as four out of six animals deceased. Subsequent in vivo experiment conducted to verify the role of cytokines secreted during early periods of bone induction revealed that inflammatory cytokines play a limited role in osteogenic differentiation of progenitor cells. Orthotopic experiments conducted in critical sized bone defects in canine model indicate that high surface area and adsorption of proteins to the scaffolds could relatively influence bone induction. On the basis of experiments conducted, this thesis concludes that osteoinduction occurs after the inflammatory phase and is minimally influenced by inflammatory factors.