Grant: $500,000 - National Science Foundation - Aug. 6, 2009
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Award Description: Although spinal cord injury is a relatively rare occurrence (affecting about 11,000 people annually in the US), these debilitating injuries occur most commonly in young people who go on to live for many decades with extreme health complications, compromised quality of life, and immense medical costs. No current therapies exist to induce complete spinal cord regeneration; however, the clinical community suggests that a combined approach involving biodegradable materials, cell transplantation, and drug delivery offers the best hope. Towards this broader goal, the focus of my research is to develop new design strategies for adaptable biomaterials that undergo predictable, cell-induced remodeling. All of these materials are fabricated using recombinant protein engineering technology, which allows precise molecular-level control over the entire primary structure. Due to this exquisite level of control, the initial mechanical properties, degradation profile, and cell adhesivity of the biomaterial can be independently and exactly tuned. Through precise design of these adaptable biomaterials, we enable dynamic two-way communication to occur between the biomaterial and embedded cells. This two-way cell-scaffold communication will be studied using neural progenitor cells encapsulated within our adaptable biomaterials. In Aim 1, the relationship between initial biomaterial properties (elasticity and cell-receptor-ligand density) and cell phenotypic response (three-dimensional neurite outgrowth and protease enzyme secretion) will be determined. We hypothesize that neurite outgrowth can be directed through material design. In Aim 2, we will develop a theoretical model to predict degradation profiles and compare this model to experimental measurements of cell-induced remodeling. We hypothesize that cell-scaffold interactions can be dynamically controlled through precise local tuning of the degradation rate. In Aim 3, we will explore the use of cell-induced remodeling as a trigger to release peptide-pharmaceuticals from biomaterials. We hypothesize that tailoring of the biomaterial degradation rate and the peptide diffusion rate will provide predictable delivery profiles. The Intellectual Merit of this program lies in its unique approach to biomaterials design encompassing the entire service-life of the material. As clinical medicine relies more heavily on implanted materials for regenerative therapy, drug delivery, and prosthetics, the engineering of the degradation properties of the biomaterial as well as the initial biomaterial properties becomes critical. This program provides new strategies to precisely control the rate of formation and composition of biomaterial degradation fragments independent from other material properties. As they degrade, these biomaterials adapt to and alter the cellular micro-environment, providing a dynamic method to control cell-scaffold responses. Therefore, this work will make fundamental contributions to the field of biomaterials. The Broader Impact of this program includes an Integrated Education Plan that promotes teaching and learning across multiple groups. At the high school level, students from under-represented groups will participate in hands-on research, share their experiences with peers and teachers in the classroom, and receive continued mentoring as they embark on their collegiate careers. Success of this new program will be assessed with help from the Stanford Office for Science Outreach, and results will be disseminated at national conferences and in engineering education journals. The Integrated Education Plan also includes activities to promote diversity and interdisciplinary training for undergraduate and graduate students through new course development as well as formal and informal mentoring programs. Our research impacts the broader scientific community by providing new approaches to design highly tailored biomaterials with adaptive properties.
Project Description: As defined in the Award Description field.
Jobs Summary: Faculty, Research Assistant (Total jobs reported: 1)
Project Status: Less Than 50% Completed
This award's data was last updated on Aug. 6, 2009. Help expand these official descriptions using the wiki below.