Reconstituted Collagen Produces Different Healing Reactions in Bony and Soft Tissue Compartments
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RECONSTITUTED COLLAGEN PRODUCES DIFFERENT HEALING REACTIONS IN BONY AND SOFT TISSUE COMPARTMENTS
REYNALDO TODESCAN AND JOHN E. DAVIES Centre for Biomaterials, University of Toronto, 170 College Street, Toronto, ON, M5S 1A1, Canada. ABSTRACT Using both in vivo and in vitro experiments we have demonstrated that: reconstituted collagen will undergo mineralization in a healing bony compartment; that this mineralization is the result of spontaneous precipitation of calcium salts due to the presence of alkaline phosphatase produced by the bone cells, and that once calcified, the collagen will undergo cellular resorption by tartrate-resistant multi-nucleate giant cells similar to osteoclasts. This sequence of events is quite different to that in the supra-bony soft-tissue compartment where no calcification of the collagen is apparent, the collagen matrix becomes infiltrated with fibroblast-like cells and little resorption of the matrix occurs during implantation. We conclude that reconstituted collagen may be employed as both a tissue barrier, enhancing guided tissue regeneration, and a bone-substitute material, which becomes replaced by natural bone tissue. INTRODUCTION We have shown that bovine dermal collagen (BDC) improves bone healing around endosseous dental implants in a fresh extraction site rat model [1]. Our results suggested a differential tissue response to implanted collagen in bony and supra-bony compartments. By 6 weeks post-implantation, BDC was replaced by bone in the bony site, below the level of the alveolar crest, while in the supra-bony site, the BDC remained and was colonized by fibroblast-like cells (Fig 1). Furthermore, some initial in vitro experiments demonstrated that bovinederived collagen, would also become calcified in the presence of alkaline phosphatase positive bone-derived cells [2]. From these initial results we hypothesized that not only would the reconstituted collagen in the supra-bony compartment provide a tissue barrier and thus improve bone healing but that the reconstituted collagen in the bony compartment would, due to the specific action of osteogenic cells in the healing bed, also undergo calcification prior to being resorbed and replaced by bone tissue. We describe herein a series of experiments that demonstrate the sequential response of bone cells to reconstituted collagen and that bone will create a unique environment which is instrumental in generating these observed responses. MATERIALS AND METHODS Reconstituted bovine dermal collagen was used in both the in vivo and in vitro experiments outlined below. For the in vivo studies, ZydermTM a fibrous, reconstituted dispersion of bovine dermal collagen (95-98% of type I and traces of type III collagen) in physiological saline solutin`, was used at concentration of 35 mg/ml. For the in vitro studies Vitrogen , a pepsin-solubilized bovine dermal collagen, was prepared and used in the gel form of native collagen fibers at a final protein concentration of 2.0 mg/ml. Both products were obtained from Collagen Corporation, Palo Alto
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