Growth factor-delivering nano-fibrous scaffolds for bone tissue regeneration.

Abstract

Despite the demonstration of various engineered tissues, clinically useful bone tissue regeneration remains a challenge. Osteogenic cells, a three-dimensional (3D) osteoconductive scaffold, and osteoinductive factors are integral to successful bone regeneration. Pivotal in bone regeneration will be the ability to deliver appropriate growth factors in a controlled manner using 3D scaffolds and advanced release technologies within a tissue engineering strategy. The overall goal of this dissertation is to develop a growth factor delivering 3D scaffold platform for bone tissue regeneration. First, we have developed a phase separation/sugar sphere template leaching technique to fabricate 3D porous scaffolds which mimic natural bone extracellular matrix in structure, morphology and/or composition. The novel scaffolds possess high porosities, interconnected macropores, and collagen resembling nano fibers. The technique advantageously controls macropore shape and size by sugar spheres, interpore opening size by sugar template assembly conditions, and pore wall morphology by phase separation parameters. The interconnected macroporous and nano-fibrous scaffold is designed to provide an advantageous environment for cell attachment, proliferation and differentiation. In addition, the biomimetic growth of bone-like apatite crystals in scaffold was investigated in simulated body fluid and the apatite coated scaffolds demonstrated improved mechanical properties and bioactivity. Second, biodegradable micro/nanospheres are prepared for the controlled release of several biological molecules including parathyroid hormone (PTH), recombinant human platelet-derived growth factor-BB (rhPDGF-BB) and bone morphogenetic protein (rhBMP-7). The released proteins were biological active to stimulate corresponding cellular functions. Furthermore, a 3D scaffold delivery system has been developed by immobilizing growth factor (rhPDGF-BB or rhBMP-7) containing nanospheres onto a scaffold. <italic>In vitro</italic>, different biodegradable nanospheres have been utilized to individually control the release profiles of the growth factors from 3D scaffold. <italic>In vivo</italic>, enhanced ectopic bone formation has been demonstrated in rhBMP-7 delivering nanosphere-scaffold. The nanosphere-scaffold technology platform is further expanded to deliver multiple proteins from one single scaffold, each with individualized release profile. Multiple proteins released from a single scaffold over days, weeks, and months are demonstrated. In summary, this dissertation demonstrates the successful generation of a biomimetic scaffold capable of controlled growth factor delivery which indicates significant potentials in tissue engineering and regenerative medicine.