Stanford ChEM-H solicited proposals from Stanford faculty members who are interested in the design, engineering, and testing of new materials for applications in biology and medicine. Two proposals were selected based on their potential to develop biomaterials as platform technologies that can broadly impact biological and/or pharmacological science. Each project will research two years of funding for a total of $125,000 beginning in August 2014.
"Protein-Engineered Hydrogels for Improved Efficacy of Stem Cell-Based Injection Therapy in a Murine Model for Peripheral Arterial Disease"
Ngan Huang, Cardiothoracic Surgery
Sarah Heilshorn, Materials Science & Engineering
Two of the most critical bottlenecks in any cell-based therapy are the ability to deliver clinically relevant numbers of cells into their site of action and maintaining their viability in situ. Because the number of viable cells at the desired site of regeneration has been correlated with symptomatic relief, it is critical to develop strategies to more efficiently deliver cell-based therapies. Local delivery of cells, achieved by direct syringe-needle injection, is the least invasive method of cell-delivery; however, it commonly results in less than 5% cell viability post-injection, greatly inhibiting clinical outcomes. To address these clinical needs, we have developed Mixing-Induced Two-Component Hydrogels (MITCH), a shear-thinning and self-healing material system comprising two complementary engineered proteins that self-assemble into hydrogels upon simple mixing. When delivered in conjunction with therapeutic cells, we hypothesize that MITCH will enhance cell viability when injected to sites of tissue ischemia. We will apply MITCH towards injection of human induced pluripotent stem cell-derived endothelial cells (iPSC-ECs) for treatment of peripheral arterial disease (PAD). PAD patients have obstructed blood flow to the lower extremities, so enhancing angiogenesis using iPSC-ECs may be a promising treatment, and maintaining the viability of these cells is critical to their efficacy.
Dr. Huang is an Assistant Professor in Cardiothoracic Surgery, and her laboratory focuses on studying the role of extracellular matrix interactions on stem cell behavior. Her laboratory aims to quantify the chemical and biophysical interactions between stem cells and extracellular matrix (ECM) proteins that regulate cell fate specification, function, and survival. Dr. Heilshorn is an Associate Professor of Materials Science & Engineering, and her laboratory studies the design of materials and scaffolds that mimic the micro- and nano-scale order found in nature for tissue engineering applications. This collaboration brings together multi-disciplinary expertise for solving a critical bottleneck in regenerative medicine.
"Engineering Dual-Gradient Hydrogels for Elucidating Cell-Niche Interactions"
Fan Yang, Bioengineering & Orthopedic Surgery
Stuart Goodman, Orthopedic Surgery
Many essential biological processes are mediated by gradients of biochemical and mechanical properties of extracellular matrix. Furthermore, most tissue interfaces are characterized by transitions of biochemical and mechanical niche cues in a gradient manner. However, how such gradient niche cues influence cellular fates and tissue development remains largely unknown. To overcome these limitations, the goal of this proposal is to develop biomimetic hydrogels with dual gradients of mechanical and biochemical cues to elucidate the effects of interactive niche signaling on stem cell fates. Furthermore, our proposed dual gradient hydrogel platform can facilitate high-throughput apid discovery of optimal niche cues that promote desirable cellular fates using minimal amounts of cells and materials. While the proposed work will initially focus on stem cell differentiation towards bone pathway as a model system, the proposed materials platform is very versatile and can be applicable to study a broad range of cell types and biological processes such as wound healing, inflammation, cancer and tissue regeneration.
This project leverages on an established interdisciplinary team with complementary expertise in stem cells, biomaterials, tissue engineering and medicine. Prof. Fan Yang (PI), is an Assistant Professor in Orthopaedic Surgery and Bioengineering, and she has extensive experience in developing biomaterials platforms for understanding stem cell-niche interactions and developing tissue engineering therapies for treating degenerative diseases. Dr. Yang’s achievements have been recognized by over 20 honors and awards, including one of 2011 TR35 Global list honorees by Technology Review, which recognizes the world’s 35 most outstanding innovators who are younger than 35, whose superb technical work promises to shape the coming decades. Prof. Stuart Goodman (Co-PI), is the Robert and Mary Ellenburg Professor of Surgery, and Professor of Orthopaedic Surgery. As an academic orthopaedic surgeon, Dr. Goodman specializes in bone biology, development and tissue repair for over 25 years. As an NIH funded PI, Dr. Goodman has led a basic science lab in exploring pertinent scientific questions that have direct translation to patient care.