Engineering Biomimetic Microenvironment for Regenerative Medicine and Disease Models

In most living tissues, cells typically reside in a microenvironment where they interact with the extracellular matrix (ECM) as well as neighboring cells. The ECM, constructed from diverse, nano-sized biomacromolecules, often displays topography at nanoscales. The fibrous proteins penetrate through a matrix composed of proteoglycan and interstitial fluids to form a three-dimensional (3-D) gel-like network. Depending on ECM composition and interstitial fluids, the ECM exhibits various degrees of stiffness. These microenvironmental cues critically influence numerous developmental, physiological and pathological processes in vivo, and have been applied to modulate almost all aspects of cell behavior in vitro. Thus, developing a fundamental understanding of how the microenvironmental cues regulate cell behavior will provide important mechanistic insight and lead to advancement of cell culture technologies and identification of potential therapeutic and pharmaceutical targets for a variety of diseases.

From biomaterials and polymer micro-/nanoengineering approaches, we are able to engineer biomimetic microenvironments and study cellular responses to the defined microenvironmental cues. We fabricated a variety of nanotopographies covering primary shapes and important dimensional parameters , and investigated how nanotopography modulated cell behavior, from cell adhesion, spreading and migration, to proliferation and differentiation. We also examined the influence of substrate stiffness on cellular responses to engineered nanomaterials. In addition , we integrated nanotopography into a microfluidic platform and applied nanotopography and fluid shear stress to manipulate cell behavior. We further extended our understanding of 2-D cell-substrate interactions to create 3-D tumor microenvironment for chemoresistance study of acute lymphoblastic leukemia. Through cellular studies using the engineered biomimetic microenvironments, we expect to provide insight into the rational design of new biomaterials and surfaces of implants and medical devices for regenerative medicine and to advance our understanding and treatment of human disease.