(554e) Application of Hydrogen Sulfide Releasing Materials in Complex Bone Regeneration

Critical size bone defects are large volume fractures that can cause result in nonunion or malunion especially in elderly and osteoporotic patients. Bone tissue engineering offers a promising approach for stimulating bone regeneration via osteoinductive materials such as calcium phosphates. In specific, it is known that the calcium and phosphate ions released from these biomaterials govern its dose-dependent bioactivity and cytotoxicity. To expedite and improve overall bone fracture repair, it is desirable to deliver large quantities of these bioactive molecules, but this is coupled with significant increases in reactive oxygen species production leading to significant oxidative stress. To address this toxicity issue, we have focused on co-delivering hydrogen sulfide to allow for cells to tolerate greater quantities of calcium and phosphate ions. First, we investigated the concentration-dependent effects of hydrogen sulfide on in vitro proliferation and viability of mesenchymal stem cells. Then, we used the therapeutic window determined from this work to investigate the cytoprotectant effect of hydrogen sulfide in the presence of toxic but highly inductive concentrations of calcium and phosphate ions. Finally, we used the data from this work to design and synthetize polymers capable of controlled bioactive molecule release to achieve optimal proliferation and differentiation outcomes in vitro.