| dc.description.abstract | In the United States, an estimated of 1.5 million individuals suffer from bone fractures annually. Among these bone fractures, intra-articular fractures (e.g., tibia plateau fractures) involve a weight-bearing joint which is subjected to repetitive, dynamic physiological loading from daily activities, thus are more challenging to treat. There is a compelling need for bone grafts that provide bone-like strength, stimulate osteogenic differentiation and mineralization of osteoprogenitor cells, and resorb at a rate aligned with patient biology. However, currently available grafting materials fall short of these targeted properties. Biomaterials that provide both biological functionality and load-bearing capability are currently not available.
The goal of this dissertation was to develop polyurethane (PUR) based bone grafts that possess both biological functionality and load-bearing capability for treatment of bone defects at weight-bearing sites. To meet this goal, novel nanocrystalline hydroxyapatite (nHA)-poly(ester urethane) (PEUR) nanocomposites were synthesized by a solvent-free grafting reaction and two-component urethane chemistry. The nHA-PEUR nanocomposites were fabricated by simple mixing using a two-component syringe, exhibited bone-like strength, stimulated osteoblast mineralization, and resorbed in response to osteoclasts and the oxidative microenvironment associated with bone remodeling. The nHA-PEUR nanocomposites were further incorporated with micron-sized ceramic granules to make settable, weight-bearing bone grafts. The bone grafts were implanted in weight-bearing sheep tibial plateau slot defects and non-weight-bearing sheep femoral plug defects to test if they maintain mechanical stability as being resorbed under physiological loading and to investigate the effects of mechanical loading on graft remodeling. Additionally, a standardized, quantifiable in vitro method to analyze relative osteoclast resorption rates on synthetic substrates was developed. Rates of resorption of the substrates relative to that of dentin were calculated from optical profilometry measurements of resorption area at three time points. This method will aid in the design of biomaterials that undergo balanced remodeling. Overall, this dissertation represents a potentially significant advance toward the design of biomaterials that actively heal while maintaining weight-bearing capability. | |
