Segmental bone defects frequently occur as a result of trauma, infection and tumor resection in orthopaedic and craniofacial clinical practice. Bone graft transplantation has been used as the primary treatment regimen for reconstruction of large segmental bone defects. Each year over 600,000 bone grafting procedures are performed in the United States, and more than 2.2 million are performed worldwide. Current choices for bone grafting materials include autograft, allograft, and synthetic materials. While an autograft is considered as the ?gold standard?, the use of autograft is extremely limited due to the associated donor site morbidity and the restricted availability for repair of large bone defects. Allograft remains a top choice for repair of large defects that require immediate support. However, due to the lack of viable angiogenic and osteogenic cells, healing and incorporation of bone allograft are extremely slow and limited. The limited bone forming, revascularizing and remodeling properties of structural allograft are directly associated with a 25% to 35% failure rate within 2 years and a 60% failure rate in 10 years after implantation as a result of non-union, infection and propagation of microcracks of the devitalized bone. To overcome the limitation associated with structural allograft, we proposed a tissue engineering strategy to revitalize allograft by creating a functional periosteum to enhance allograft incorporation and remodeling. With the development of a versatile electrospinning technique and a novel near-field electrostatic printing (NFEP) method, our current proposal seeks to combine several scientific and technical advances into the creation of a micro/nanofibers-based, multi-modular, prevascularized bone tissue graft, with growth factor releasing property, simulating the highly organized and functional periosteum for reconstruction of large bone defects. Incorporation of key molecular signals and relevant cellular sources that promote both osteogenesis and angiogenesis will be addressed.The completion of the project could 1) establish a novel methodology to control the spatiotemporal assembly of osteogenic and angiogenic/vasculogenic cells into a multi-functional 3-dimensional cellular construct; 2) offer mechanistic information on anastomosis and integration of engineered vascular networks with host circulation; and 3) provide the basis and means for understanding of cell-matrix interactions and for engineering of microenvironments to direct progenitor cell differentiation for bone defect repair and reconstruction. The success of our current project will also lay foundation for engineering of more sophisticated blood vessels with hierarchical patterns, which could achieve a wide impact on various tissue reconstructions. Clinically, the success of the project could further offer rationales and strategies to effectively deliver osteogenic and angiogenic/vasculogenic cell populations for enhanced repair and reconstruction of both craniofacial and long bone defects.
The project proposes to combine several state-of-the-art technologies to create a multi-modular, prevascularized bone tissue graft, with growth factor releasing property, simulating the highly organized and functional periosteum for reconstruction of large bone defects. The completion of the project will establish a novel strategy to enhance vascularization of engineered bone constructs; further offering a tissue engineering solution and a translational therapeutic strategy to enhance bone defect repair and reconstruction.
