Injectable biomaterials which undergo a transformation from a fluid to a solid or semi-solid in-situ are potentially useful as reconstructive and therapeutic materials in numerous craniofacial and dental surgical procedures. Biomimetic strategies are designing new reconstructive biomaterials can be inspired by the underling biochemical and biophysical processes which occur during mineralized tissue formation. The long term goal of this research is to employ the bioinspired strategy of in-situ self-assembly to form a collagen-mineral composite biomaterial. Recently, we have shown that the compartments of synthetic phospholipid vesicles (liposomes) can be exploited to control mineral formation in a calcium phosphate solution. We designed liposomes which sequestered Ca at room temperature but released Ca rapidly when heated to body temperature. Highly supersaturated solutions consisting of Ca loaded liposomes suspended in aqueous sodium phosphate were found to be unreactive under ambient conditions, but rapidly formed calcium phosphate minerals when heated to body temperature. In this research we will exploit the difference between ambient and body temperature to trigger in-situ formation of a composite biomaterial. Our general hypothesis is that the dual processes of thermally triggered liposomal mineralization and thermal gelation of type 1 collagen can be exploited to form a self-assembling collagen/mineral composite biomaterial with useful clinical properties. The following specific aims are designed to test these hypotheses, and to determine the structure-property relationships of these biomaterials: 1) Prepare phosphate-containing liposomes and study their use in combination with calcium-loaded liposomes for thermally-triggered formation of calcium phosphate minerals. 2) Combined liposome-mediated thermal mineralization with thermal gelation of type I collagen to create an in-situ forming collagen/mineral biomimetic composite. 3) Utilize scanning and transmission electron microscopy to determine collagen network structure and mineral-collagen interactions on composite properties. 4) Utilize dynamic mechanical analysis to determine the effect of mineral content, collagen structure, and mineral-collagen interactions on mechanical strength.
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