Geometry of carriers controlling phenotypic expression in BMP-induced osteogenesis and chondrogenesis

Background: The effect of the geometry of extracellular matrices on bone mo rphogenetic protein (BMP)-induced osteogenesis has not been systematically studied. Geometry is crucially important for the:scaffold in bone and joint tissue engineering. The purpose of this study was to elucidate principles of geometry of matrices in designing new scaffolds and matrices for use in reconstruction of bone and joints. Methods: More than ten biomaterials with different geometries, including a unique device of honeycomb-shaped hydroxyapatite, were combined with BMPs o f recombinant (rhBMP-2) or natural bovine origin (S300 BMP cocktail) and im planted subcutaneously into LF-week-old Wistar-King rats. The implanted pel lets were removed at 1-4 weeks and analyzed for bone and cartilage formatio n by histological and biochemical methods. Results: BMP-induced bone and cartilage induction was highly dependent on t he geometric properties of the carrier. Some carriers such as porous partic les or blocks of hydroxyapatite induced osteogenesis directly, without dete ctable chondrogenesis, whereas other carriers such as fibrous glass membran e induced cartilage exclusively. Still other carriers induced mostly cartil age followed by bone formation. Solid particles of hydroxyapatite and fibro us glass membrane with too tight a meshwork did not induce bone or cartilag e. The optimal pore size for bone-forming efficacy in porous blocks of hydr oxyapatite was a diameter of 300-400 mum. In straight tunnel structures wit h various diameters in honeycomb-shaped hydroxyapatite, tunnels with smalle r diameters (90-120 mum) induced cartilage followed by bone formation, wher eas those with larger diameters (350 mum) induced bone formation directly w ithin the tunnels. Conclusions: BMP carriers were classified into three types: bone-inducing, cartilage-inducing, and cartilage-bone-inducing. From the analysis of causa tive factors inducing osteogenesis and chondrogenesis in the BMP system, we concluded that the geometry of the carrier is crucially important and vasc ulature-inducing geometry should be considered in designing effective scaff olds for bone formation. We propose a classification of geometry of the art ificial extracellular matrices that is useful for designing a scaffold for tissue engineering of bone and related tissues. Clinical Relevance: Conventional requisites of the BMP carriers for clinica l use have mainly concerned the affinities of carriers with cells and biomo lecules and their mechanical strength. The vasculature-inducing geometry of carriers adds a new criterion in designing systems for effective bone and joint reconstruction. The geometries of porous structures-their sizes, cont inuity, and straightness as verified by hydroxyapatite in this study-will b e applicable for other biomaterials for clinical reconstruction therapy.