Bone regenerative engineering via controlled release of simple signaling molecules

[ACCESS RESTRICTED TO THE UNIVERSITY OF MISSOURI AT AUTHOR'S REQUEST.] More than 1.7 billion people worldwide are suffering from bone defects that are due to trauma or medical conditions such as degenerative diseases. Bone can repair and remodel itself, however, in the case of critical size defects, healing is impossible without intervention. Bone regenerative engineering is a new field that focuses on the development of bone substitutes that can stimulate the body to remodel bone tissue in the defect site, most commonly utilizing calcium phosphates in their design to mimic the inorganic phase of bone. Most of previous research has overlooked that calcium phosphates consist of two non-proteinous signaling molecules calcium ions (Ca2+) and phosphate ions (Pi) which are referred as simple signaling molecules that are osteoinductive in a time-dependent and concentration-dependent manner. Higher concentrations of these ions are not only non-inductive, but are also cytotoxic. In my PhD research, I first identified the therapeutic range of Ca2+ and Pi after which I developed two novel platforms capable of controllably delivering these ions within their inductive therapeutic windows. The first platform was comprised of synthetic, hydrophobic, five-carbon polyesters incorporated with rapid dissoluting monobasic calcium phosphate as a scaffold for critical size defects in long bones. The second platform consisted of natural, hydrophilic, chitosan-based hydrogels incorporated with slow dissoluting dibasic calcium phosphate for the treatment of vertebral compression fractures. While I established a new aspect for controllably delivering Ca2+ and Pi as bioactive additives for different bone tissue engineering applications, we are interested in other simple signaling molecules as well. Moving forward, our research group is interested to investigate the effect of hydrogen sulfide (H2S), hydrogen peroxide (H2O2), and carbon monoxide (CO) as cytoprotective, angiogenic, and neuroinductive simple signaling molecules, respectively. The spatiotemporal delivery of multiple simple signaling molecules can be promising for complex bone tissue engineering applications.