(742f) Complex Bone Regeneration Via Controlled Release of Simple Signaling Molecules

A growing number of patients are suffering from disabilities related to bone defects such as fracture nonunion. Tissue engineering offers a promising approach to enhance host bone regeneration with most of these methods have focused on developing osteoinductive biomaterials. However, because of complexity of bone tissue and its vast neurovascular network, the vast majority of these strategies have not been successfully translated to the clinic. The goal of this research is to develop novel biomaterials which are capable of inducing neurogenesis and angiogenesis along with osteogenesis in critical size bone defects. Upstream, non-proteinaceous inductive chemicals termed simple signaling molecules were utilized in this research because they are less expensive and easier to process and manipulate compared to more commonly utilized downstream growth factors. Specifically, we have investigated osteoinductive calcium and phosphate ions, angioinductive hydrogen peroxide, and neuroinductive carbon monoxide and hydrogen sulfide. In the current research, we have first focused on the concentration-dependent effects of simple signaling molecules on in vitro differentiation of stem cells. We have then leveraged the therapeutic windows determined from this work to design and synthesize unique polymers capable of achieving desirable controlled release of these inductive molecules to achieve optimal cell differentiation outcomes.