Implantable materials for regenerative medicine:   We are designing a new family of biomaterials that are made entirely of engineered proteins. By carefully selecting the primary amino acid sequence of our engineered proteins, we can create biomaterials with independently tunable biochemical and biomechanical properties that mimic many of the essential properties of natural tissues including elasticity, proteolytic remodeling, and cell binding and signaling.  An essential component of these engineered protein-based materials are elastin-like peptide sequences that provide excellent mechanical resilience. These elastin-like biomaterials are being investigated for use both as ex vivo tissue mimics to study the fundamentals of cell-matrix interactions and as in vivo tissue mimics for regenerative medicine applications. Current systems under study include neuronal, cardiac, vascular, and bone tissues amongst others.

(Patrick Benitez, Cindy Chung, Kyle Lampe, Jordan Raphel, Nicole Romano) Digital artwork provided by Chelsea Castillo

Injectable matrials for cell transplantation:   Cell transplantation has great potential for treating a wide variety of human diseases and injuries; however, due to a local inflammatory microenvironment and mechanical damage during the injection procedure, cell viability following simple injection protocols remains low. We are developing functional cell delivery materials to protect cells from mechanical stress during injection, localize them to the transplantation site, and direct their organization and differentiation in vivo. Our engineered materials are built from two classes of engineered proteins that create physically crosslinked hydrogels when mixed under constant physiological conditions. These Mixing-Induced X-linking (MIX) hydrogels allow cytocompatible 3D cell encapsulation and are shear-thinning and self-healing, making them ideal injectable vehicles for delivering encapsulated cells to a therapy site.

(Lei Cai, Karen Dubbin, Midori Greenwood-Goodwin, Widya Mulyasasmita, Andreina Parisi-Amon) Digital artwork provided by Chelsea Castillo

In vitro mimics of tissue architecture: In spite of recent significant achievements identifying and controlling stem cell differentiation, maintenance, and proliferation, fundamental interactions between the microenvironment and stem cells in vitro represent an urgent area for investigation due to several limitations: 1) lack of preservation of appropriate 3D tissue architecture, 2) ill-defined physiological parameters for in vitro culture, and 3) unclear knowledge of cell-cell interactions during co-culture of stem cells with neighboring cell types. We hypothesize that these limitations may be addressed through use of customizable biomimetic protein scaffolds that mimic the native stem cell niche to provide direct control over in vitro stem cell cultures. To test our hypothesis, we are focusing on the recapitulation of the intestinal stem cell niche in collaboration with Prof. Calvin Kuo at the Stanford School of Medicine. 

(Becky Snyder)

Microfluidics for cell migration and chemotaxis:   Microfluidic devices are tools capable of recreating natural microenvironments of cells and tissues in a controllable and reductionist manner. Here, we implement these helpful devices to study the mechanism of 2D and 3D cellular responses to stable gradients of soluble biochemicals. Because these devices are fabricated from optically clear materials, we can visualize cellular dynamics, including cell motion, cell morphology, and receptor localization, within a variety of biomaterial scaffolds and biochemical gradients. Current projects cover a wide range of medically relevant cellular activities including endothelial cell migration and sprout formation, neuronal axon navigation, immune cell chemotaxis during infection, and stem cell chemotaxis and differentiation.

(Ruby Eka Dewi, Meghaan Smith) Digital artwork provided by Chelsea Castillo

Biotemplates for inorganic nanoparticles:   Nature presents us with an amazing variety of exquisite, self-assembling nano-scale architectures. Recently, several methods have been developed to interface biological structures with inorganic materials, using the biological molecules as templates to fabricate nanowires and nanospheres with unprecedented order and regularity. Although several biological systems have been explored as biotemplates, a flexible platform capable of templating a variety of 2D and 3D ordered structures has not yet been developed. Our goal is to engineer a versatile protein biotemplate at the molecular level to create 2D and 3D conducting nanostructures for energy applications.

(M.A. Arunagirinathan, Kelly Huggins, Alia Schoen)