CAREER: Adaptive Biomaterials that Enable Cell-Induced Remodeling and Drug Release

Stanford University, Stanford CA

Investigators

Abstract

ID: MPS/DMR/BMAT(7623) 0846363 PI: Heilshorn, Sarah ORG: Stanford Title: CAREER: Adaptive Biomaterials that Enable Cell-Induced Remodeling and Drug Release This award is funded under the American Recovery and Reinvestment Act of 2009 (Public Law 111-5). INTELLECTUAL MERIT: 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 this project 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, dynamic two-way communication is enabled between the biomaterial and embedded cells. This two-way cell-scaffold communication will be studied using neural progenitor cells encapsulated within these 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. The PI hypothesizes that neurite outgrowth can be directed through material design. In Aim 2, the PI will develop a theoretical model to predict degradation profiles and compare this model to experimental measurements of cell-induced remodeling. It is hypothesized that cell-scaffold interactions can be dynamically controlled through precise local tuning of the degradation rate. In Aim 3, the PI will explore the use of cell-induced remodeling as a trigger to release peptide pharmaceuticals from biomaterials. It is hypothesized that tailoring of the biomaterial degradation rate and the peptide diffusion rate will provide predictable delivery profiles. BROADER IMPACTS: 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. The research impacts the broader scientific community by providing new approaches to design highly tailored biomaterials with adaptive properties. Currently, no general strategy exists to control the rate of biomaterial adaptation after implantation. These types of adaptive biomaterials are required to develop therapies for spinal cord regeneration and may guide the way towards future prosthetic interfaces that integrate with host tissue, such as implanted prosthetics that grow with a child.