Development of Bioactive Nanocomposites for Bone Tissue Engineering Applications

Monday, 17 February 2014
Columbus CD (Hyatt Regency Chicago)
Declan Devine , Beth Israel Deaconess Medical Center, Boston, MA
Bone has a remarkable capacity to heal. However, in some instances the amount of bone which is needed to heal exceeds its healing capacity. These cases arise following accidents, infection or surgery to remove cancerous tissue and they result in the need to perform approximately 2.2 million surgical bone grafting procedures annually. These procedures have inherent disadvantages and so there is an urgent clinical need to develop a tissue engineering alternative to bone grafting.

Within this field Calori et al. 2011 have proposed that the healing of bone can be enhanced using what they coined the ‘Diamond theory’ where they discuss the interconnecting role of the mechanical stability, vascularity, osteoprogenitor cells, growth factors and the scaffold in the healing of bone defects. Thus, to create a truly biomimicking scaffold all of these factors need to be addressed to some level if a tissue engineering approach is to succeed. While, growth factor treatments are clinically available in the form of Medtronics Infuse® (Bone Morphogenetic Protein-2; BMP-2) and Strykers OP-1® (BMP-7) they are currently applied as a two part system where the liquid growth factor is added to a collagen scaffold at supra-physiological doses for implantation. However, these scaffolds do little to retain the growth factor within the surgical site in the dynamic bleeding environment required to optimise healing and it has been reported that the collagen may actually affect the pharmacokinetics of the growth factor. Nevertheless, despite their limitations these treatments do enhance bone formation but this bone cannot survive without the supply of nutrients from the vascular bed and without this the bone will be resorbed.

In the current study a chitosan/hydroxyapatite composite scaffold is been developed to meet the requirements set out by Calori and overcome current issues with growth factor treatments. The mechanical stability of the scaffold has been optimised to maximise the mechanical stability of the construct whereas the issues of vascularity, growth factors and the response of host osteoprogenitor cells will be regulated through the sustained action of growth factors. To date scaffolds have been shown to be non-toxic pre-osteoblastic cell lines and they are capable of sustaining the release of a model protein for a minimum of 10 days. Work is continuing and data will soon be available in relation to the sustained release osteogenic and neovascular promoting growth factors alone and in combination.