Biomimetic Porous Scaffolds with High Elasticity Made from Mineralized Collagen—An Animal Study Atsuro Yokoyama, 1 Michael Gelinsky, 2 Takao Kawasaki, 1 Takao Kohgo, 1 Ulla Ko ¨ nig, 2 Wolfgang Pompe, 2 Fumio Watari 1 1 Graduate School of Dental Medicine, Hokkaido University, Kita 13, Nishi 7, Kita-Ku, Sapporo 060-8586, Japan 2 Max Bergmann Center of Biomaterials, Technical University Dresden, Institute of Materials Science, Budapester Strasse 27, D-01069 Dresden, Germany Received 10 November 2004; revised 11 February 2005; accepted 28 February 2005 Published online 25 July 2005 in Wiley InterScience (www.interscience.wiley.com). DOI: 10.1002/jbm.b.30331 Abstract: Histological investigations of a new hydroxyapatite– collagen composite material were carried out to evaluate its possible suitability as a bone substitute. The three-dimensional scaffolds made from biomimetically mineralized collagen exhibit an interconnecting pore structure and elastic mechanical properties. They were implanted into the subcutaneous tissue and bone defects made in the femur of rats and harvested with the surrounding tissue at 1, 2, 4, 8, and 12 weeks after surgery. The materials implanted in the subcutaneous tissue were covered by fibrous connective tissue with a slight inflammatory response, and many foreign- body giant cells were observed on the surface of the scaffolds. Most of the material implanted in the subcutaneous tissue was resorbed at 8 weeks by phagocytosis. In the bone defects, new bone formation was observed on the surface of the material at 1 week. New bone increased with time, and osteoclasts were seen on the surface of the scaffolds at 2 weeks. Resorption and replacement by new bone of many parts of the materials implanted in the femur were observed by 12 weeks. These responses occurred faster than those of other hydroxyapatite-collagen composites. The results suggested that the new biomimetically mineralized collagen scaffolds were suitable as an implant material for bone-tissue reconstruction. © 2005 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater 75B: 464 – 472, 2005 Keywords: biomimetic; bone; collagen; hydroxyapatite; composite/hard tissue INTRODUCTION Many different synthetic materials are used as bone substi- tutes. Each of these has its advantages, but also disadvantages such as the acidic degradation products of polymers such as polylactide 1 or the slow biodegradation of sintered hydroxy- apatite ceramics. 2 For many clinical purposes the autologous bone graft is therefore still the gold standard because of its good and fast integration into the surrounding tissue, the rapid remodeling to new bone, and the lack of immunological problems. But harvesting of the autologous bone such as the iliac crest requires a second operation with all its risks, possible pain for the patient, and the difficulty of obtaining a large quantity of bone. Therefore many groups have tried and are still trying to develop a synthetic material that mimics the composition and structure of the extracellular bone matrix, which mainly consists of collagen type I fibrils, mineralized with hydroxyapatite (HAP) nanocrystals, as an alternative to the use of autologous grafts. At the very beginning, simple mixtures of collagen and HAP granules were developed with the aim of improving the handling of calcium-phosphate particles during surgery. 3 Early approaches to synthesize real collagen–HAP composites as implant materials were made by TenHuisen et al., but the material they reported about in 1995 was more a calcium-phosphate bone cement with collagen fibers incorporated in it than a bone-like nanocomposite. 4 During the following years, many other groups published their concepts on more or less biomimetic collagen–HAP composites and bone-replacement materials produced out of them, but most of them applied nonphysiological conditions (temperature above 38°C or strong basic pH) which may lead to a denaturation of the collagen component. 5–13 A biomi- metic method has been developed to produce such a compos- ite under nearly physiological conditions (37°C and pH 7) where the collagen fibril assembly and the crystallization of HAP nanoparticles occurs simultaneously. 14,15 The fabrica- tion of a membrane-like material that exhibits pores only in the micrometer range and might therefore be useful for the separation of tissues (collagen–HAP tape) has already been Correspondence to: Atsuro Yokoyama (e-mail: yokoyama@den.hokudai.ac.jp) Contract grant sponsor: Bundesministerium fu ¨r Bildung und Forschung Contract grant sponsor: BIOMET Europe GmbH; contract grant number: 3N4020 © 2005 Wiley Periodicals, Inc. 464