SUMMARY

Nonunion of large bone defects poses a common clinical challenge. Autografts and allografts, two current clinical therapies for treating large bone defects, both possess shortcomings and leave a need for a better treatment method. Bone tissue engineers aim to fill this need by creating constructs consisting of some combination of scaffold, cells, and / or growth factors. Defect site delivery of stem cells that can differentiate into bone cells can enhance healing of bone defects. A large portion of people requiring bone grafts, including the sick and elderly populations, may lack a sufficient endogenous stem cell population to contribute to bone growth. Although a variety of stem cell sources and delivery methods have been investigated for bone repair, results have been inconsistent and few comparative studies have been done within the same model. The goals of my research are to: 1) Establish a challenging large bone defect model in immuno-compromised nude rats for evaluation of human stem cell delivery and tracking. Cell survival and distribution after delivery will be tracked by labeling cells with fluorescent quantum dots 2) Quantitatively compare the abilities of human adult (mesenchymal) and fetal (amniotic fluid) stem cells to enhance healing of defects. 3) Evaluate the effects of added stimulatory cues to program stem cells to differentiate towards an osteogenic lineage capable of enhancing bone formation. An adeno-associated viral (AAV) vector will be used to deliver these cues. Specifically, AAV particles capable of encoding the gene for the growth factor bone morphogenetic protein 2 will be freeze dried onto porous polymer scaffolds and delivered to the bone defect site with or without stem cells.