Collagen and Hydroxyapatite Composite Membranes as Drug-Carrying Support for Biomedical Applications
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Collagen and Hydroxyapatite Composite Membranes as Drug-Carrying Support for Biomedical Applications Daichi Kajiwara and Toshiyuki Ikoma Department of Material Science and Engineering, Tokyo Institute of Technology, 2-12-1 Ookayama, Meguro-ku, Tokyo 152-8550, Japan ABSTRACT Medical products comprised of devices and drugs have been known as a combination product. The biodegradable collagen (Col) sponges impregnated with recombinant human bone morphogenetic protein can make bone formation hasten. It is expected further features by a combination of various growth factors and artificial bone materials. The binding properties of such factors to Col and hydroxyapatite (HAp) have not been elucidate to achieve a controlled release. In this study, we investigated artificial periosteum-like membranes made from tilapia fish Col and HAp composites as a drug carrying support. The Col-HAp composites with three different compositions in weight ratio of 2:8, 5:5 and 8:2 were made and crosslinked by irradiation of gamma-ray in wet condition. The tensile strengths of the membranes in wet or dry were depended on the compositions; however the strengths of the membranes in wet were apparently weaker at 1/10 or less than those in dry at a maximum 90 MPa. The adsorption ability of proteins, bovine serum albumin (BSA) or lysozyme (LSZ), on the membranes exhibited different tendency; the membranes including higher weight ratio of HAp adsorbed BSA rather than LSZ. These results indicated that the artificial Col-HAp membranes would be the suitable materials for biomedical device as combination products. INTRODUCTION Bone grafts have been investigated to repair bone defects. There are three bone grafts, autogenous bone graft1, allogeneic bone graft2, and artificial bone graft3. The autogenous bone graft is the gold standard but lacks its amount supplied and needs an invasive treatment to patients. The allogeneic bone graft has the risk of immunogenicity and unknown pathogenicity. In contrast, the artificial bone graft can solve these problems; however it has no osteoinduction but osteoconduction, and shows lower mechanical strength compared with bone tissue4. Type I collagen (Col) is a main protein of extracellular matrixes in skin, cornea, tendon, and bone5. The mammalian Col molecules extracted from calf skin and porcine dermis have been commercialized in medical fields as scaffolds for tissue engineering6. The crosslinking of Col such as physical crosslinking and chemical crosslinking can control the mechanical properties and biodegradation rates of Col scaffolds7. Although Col shows excellent biocompatibility, Col extracted from alternative sources, a fish, have not yet been commercialized in medical fields. The porous composites of mammalian Col and hydroxyapatite (HAp) have been investigated and commercialized as bone filling materials8. The release of growth factors9 from the porous bodies which can enhance the osteogenesis and chondrogenesis in vivo have been investigated. Bone morphogenetic protein-2 (BMP-2) was adsorbed in the porous
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