NSF/DMR-BSF: Nanoparticle-Stabilized PolyHIPEs that Promote Integrin-Mediated Osteogenesis

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NON-TECHNICAL: Over one million surgical procedures are performed each year to treat bone injury and defects with an associated medical cost of over 5 billion dollars. Current procedures are fraught with problems that limit clinical success. One important approach for the treatment of bone fractures and defects is in the use of injectable fillers or cements. However, current bone cements do not adequately support bone healing, and may lead to poor clinical outcomes. This project utilizes a novel method in preparing polymers to generate an injectable bone filler that cures within the body, and forming a rigid and strong foam implant. This specially prepared polymer composite is expected to promote bone regeneration and growth by stimulating cells around the polymer. In addition to improving care for patients that suffer from traumatic bone injuries, these studies will provide exceptional training of future scientists in materials research. Educational and outreach activities will focus on strategies that enhance recruitment and retention of women and minorities in science and engineering areas in addressing the national needs to increase the participation of underrepresented groups in the scientific and engineering workforce. Finally, this Israeli-US partnership provides opportunities to train students to compete globally through a summer internship exchanges at the partnering laboratories.TECHNICAL: Current injectable bone cements used for bone fracture and repairs are of limited value because of lack of cement porosity, limited biodegradability, prolonged recovery time and lack of significant stabilization and support of the damaged bones. In addition, these synthetic scaffolds lack cellular cues to promote bone repair and regeneration, without the addition of growth factors in the injectable cements, and these involve high costs and safety concerns. To address these issues, this project will develop a novel high internal phase emulsion graft polymers (polyHIPE) using an emulsion-templating method. The graft polymers prepared will be used to generate injectable bone fillers that cure within the body to form rigid foams that are: 1) surface-modified with collagen-mimetic proteins to induce osteogenic differentiation of mesenchymal stem cells; and 2) prepared without surfactants to minimize concerns with respect to biocompatibility of leached breakdown products from these surfactants. Additionally, bioactive nanoparticles with different size, distribution, and hydrophobicity will be incorporated in these graft polymers, and these nanoparticles are expected to migrate spontaneously to the pore surface of the foam during curing process in the body. This migration of nanoparticle not only strengthen the cured polymer cement but is also expected to promote enhanced bone regeneration by stimulating cells in the polymer pores. Overall, these studies are designed such that fundamental advances will be made in synthesis and application of novel materials for the integrin-mediated osteogenesis for injectable bone grafts. Although this work is focused on bone repair and regeneration, the knowledge gained has potential to be applied to a variety of other applications such as development of membranes with well-defined pore size in battery and for water purification. Students participating in the research will receive rigorous training in material science and tissue engineering that will prepare them for careers in biomedical engineering. This collaboration with Israeli scientists would also provide opportunities in training students through a summer internship exchange at the partnering laboratory and prepare these students to compete globally. An integrated educational platform will focus on strategies that enhance recruitment and retention of women and minorities in engineering to address the national need to increase the participation of underrepresented groups in the scientific and engineering workforce.