Osteoporosis is an imbalance in the normal state of bone and results in frail bones that fracture more easily than healthy tissue. Although much of the prior research in this field has focused on prevention and/or treatment of osteoporosis, and injury research has focused on preventing falls that can cause fractures in elderly osteoporotic populations, fractures and poor healing of bone still occur at high rates. More than one third of the US population over the age of 65 experiences a fall. Falls are the leading cause of injury deaths and the most common cause of non-fatal injuries and hospital admissions for trauma among older Americans. Most fractures of the spine, hip, forearm, leg, ankle, pelvis, upper arm, and hand are caused by falls. Recently published data reinforces what many family members of the elderly already know - fractures resulting from falling reduce health related quality of life ad increase the chances that full-time health care living arrangements will be needed after hospital discharge. Research has shown that osteoporotic patients have an unusually hard time healing from a fracture because of an imbalance in bone maintenance, a process that is directed by the cells found in bone tissue. Bone healing has been studied in many types of experiments, and the cells involved have been investigated closely for changes that result from aging and osteoporosis. This research has shown that osteoporosis causes changes that prevent the cells from responding positively to bone injury. In fact, the cells are likely to produce fatty tissue rather than bone because of changes in the genes that are responsible for bone repair. While it is thought that some current products can overcome these problems and make osteoporotic bones heal better, research has shown that this is not the case. A new type of biomaterial made from keratin protein may provide a solution because it can simultaneously deliver compounds that encourage bone growth as well as direct stem cells found in bone to become bone-producing cells rather than fat-producing cells. Keratins are proteins naturally found in the human body and can be used to produce scaffolds that deliver compounds to support bone growth and offer an excellent environment for the growth of new bone, especially in osteoporotic subjects. Preliminary research has shown that keratin biomaterial can overcome some of the gene changes that result from osteoporosis and make bone-producing cells function better. The goal of this research is to test the hypothesis that a keratin biomaterial scaffold can deliver bon producing growth factor compounds directly to the site of injury where they will be taken up by the local stem cell population, and where the keratin will also encourage these cells to become bone cells rather than fat cells, further contributing to effective bone healing. The first task ofthe project will be to test the loading and delivery of two bone growth compounds, bone morphogenetic proteins 2 and 7, from keratin biomaterial scaffolds. In a second task, scaffolds made from keratin containing these compounds will be tested in a large bone defect in osteoporotic rats.
The proposed research addresses the need for better treatments for bone injury in people with osteoporosis. Treatments made from keratin biomaterials may be able to produce better bone in osteoporotic patients because they can safely deliver compounds that encourage bone growth while also directing the stem cells found in bone to become better bone-producing cells. Keratin is the only biomaterial shown to be capable of filling this dual role of compound delivery and actively directing stem cells.