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J Biomed Mater Res A. 2012 Sep;100(9):2462-73. doi: 10.1002/jbm.a.34175. Epub 2012 May 9.

Nanophase bone substitute in vivo response to subcutaneous implantation.

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  • 1Department of Otolaryngology-Head and Neck Surgery and Facial Plastic and Reconstructive Surgery, Case Western Reserve University School of Medicine, Cleveland, Ohio, USA..


A collagen-apatite composite designed as a load-bearing bone substitute implant is used to characterize the relationship between implant morphology and in vivo behavior. This nanophase bone substitute (NBS) is studied morphologically using a nondestructive imaging technique and biologically using the rodent subcutaneous model. Porosity and pore interconnectivity are correlated with histological outcomes showing cellular invasion occurs with average pore sizes below 100 μm. Crosslinking with D-ribose is shown to affect cellular infiltration in a dose-response manner. These data suggest that collagen-apatite bone substitutes can support cellular infiltration with pore size significantly smaller than 100 μm, an encouraging result regarding development of the NBS into a platform of biomaterials with enhanced mechanical properties. The data also indicate that increasing crosslinking density decreases cellular infiltration of NBS. Thus, modulating mechanical properties of the material by altering crosslink density is likely to produce decreased biological response within the material.

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