Project Details
Description
The repair and replacement of damaged hard tissues such as bone is a major clinical problem in the United States and around the world. In the United States alone, more than 500,000 hip and knee replacements are performed and over 6 million fractures are treated each year. Active duty military personnel are more prone to orthopaedic injuries involving large extremity bone injuries than civilians. Thus, there is a great need for developing biological graft substitutes with desirable biological outcome to achieve effective bone repair and regeneration. Bone autografts and allografts are the gold standard for bone defect replacement, and the preservation of the native osteogenic and angiogenic cues is one the most favorable attributes to their success as compared to other alternatives. Studies have also indicated that vascularization serves as a way of recruiting circulating osteoblast progenitors and osteoclast precursors to sites undergoing active remodeling. In order to regenerate large bone defects, a major source of nutrients, normally from a blood vessel, is indispensable. Therefore, it is critical to incorporate both angiogenic and osteogenic cues into scaffold design for successful bone regeneration. As cells in the body grow in three dimensions anchored on a network of extracellular matrix, a tissue engineering scaffold is required to recreate the extracellular matrix mimic environment. The extracellular matrix provides a three-dimensional support and interacts with cells to control their function, while guiding the spatially and temporally complex multicellular processes of tissue regeneration. Electrospun nanofiber matrices have gained tremendous interest due to their intrinsic structural resemblance to native tissue extracellular matrix. The nanofiber matrices have been shown to promote bone cell activities and enhance bone regeneration. Various approaches for biofunctionalization of bioactive motifs of the cell substratum have been utilized to modify nanofibrous scaffolds to make them closely mimic the native extracellular matrix. However, the major limitation with these approaches is that they can allow for only a few molecular cues to be incorporated into the scaffold, and thus are unable to fully recapitulate the complex extracellular environment present in the bone. Therefore, the challenge still remains to develop a scaffold that mimics the native bone extracellular matrix and vascularized bone tissue, and this has significantly hindered the progress of bone grafts for promoting bone regeneration comparable to autografts. The proposed work will focus on engineering nanofibrous scaffolds with angiogenic and osteogenic cues to achieve vascularized bone regeneration. The bone-forming cells will be cultured and decellularized to generate native bone extracellular matrix components as osteogenic cues. The cells for vascularization will be cultured and decellularized to generate native endothelial extracellular matrix components as angiogenic cues. The proposed engineered nanofibrous scaffold is composed of two continuous and connected layers -- the osteogenic nanofiber layer and the angiogenic nanofiber layer. The angiogenic nanofiber layer is prepared through electrospinning of the blend of polycaprolactone and decellularized endothelial extracellular matrix, and the osteogenic nanofiber layer is directly electroapinning the blend of polycaprolactone and decellularized osteoblast extracellular matrix onto the angiogenic nanofiber layer to form the intact engineered nanofibrous scaffolds. The proposed project consists of designing, fabricating, and characterizing the engineered nanofibrous scaffolds, and determining the efficacy of the engineered nanofibrous scaffold via in vitro culture of bone cells and cells for vascularization and in vivo experiments for bone regeneration in a bone defect model in animals. The major innovative aspect of our proposed design is the creation of improved n
Status | Active |
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Effective start/end date | 1/06/16 → … |