The percentage of the population greater than 65 years of age is expected to increase from 12.4 to 23% between the years 2000 and 2100. Not surprisingly, a similar upward trend is projected for the debilitating age-related disease: osteoporosis. Specifically, osteoporosis cases will rise from 10.1 million in 2002 to 13.9 million in 2020. Shockingly, due to the above statistics, a 300% increase in osteoporotic fractures is predicted for the next 60 years. More importantly, nationwide, approximately 1.5 million bone fractures per year are attributed to osteoporosis. None of the current methods used to treat osteoporosis have experienced overwhelming success. For example, several major barriers exist for the use of any pharmaceutical agents to stimulate new bone formation. First, the agents can cause non-specific bone formation in areas not desirable. This is because these agents are often delivered in non-specific ways (such as through the mouth, directly into the blood stream, etc.). Second, even if delivered in the general bone area, they rapidly diffuse to adjacent tissues which limit their potential to promote prolonged bone formation in targeted areas of weak osteoporotic bone. For these reasons, the long-term goal of this research is to develop novel nanostructured, self-assembled materials to fight osteoporosis. The present exploratory (high- risk, high reward) R21 proposal will begin this investigation by focusing on the use of injectable liquid self- assembled helical rosette nanotubes (HRNs) to treat osteoporotic bone. HRNs will be functionalized to specifically attach to osteoporotic over healthy bone. After attaching to osteoporotic bone, small increases in heat can be externally applied to the HRNs to transform them into a highly viscous gel-like matrix which will promote their stability in the region of osteoporotic bone. Moreover, the HRNs will be further functionalized to generate new bone formation. In this manner, the specific aims of the present proposal will involve: (i) functionalizing HRNs to attach to osteoporotic compared to healthy bone, (ii) functionalizing HRNs to increase new bone formation once attached and heat is externally applied to transform the liquid HRNs to a viscous gel-like matrix, and (iii) test the above formulated HRNs in vitro for their ability to promote new bone formation on osteoporotic compared to healthy bone. ? ?
