(4ae) Regulation of Stem Cell Behavior by Biomimetic Microenvironment Created with Polymer Nanoengineering

Stem cell therapy holds great promise for diseases that are untreatable at present, such as various gene and neurological disorders, heart and blood diseases, as well as diabetes. A key challenge is to expand and derive these cells into a specific lineage, which requires a thorough understanding of how the stem cell microenvironment controls their fate decision. My research goals are to develop a well-defined biomimetic microenvironment for stem cell research and regenerative medicine through a solid understanding of the nanoscale properties of polymers and application of environmentally and biologically benign nanoengineering techniques.

The microenvironment in living tissues comprises numerous cells, extracellular matrix (ECM) proteins and a variety of soluble and ECM-bound factors distributed in three-dimensional (3-D) space. The ECM serves as structural support and provides, in concert with the spatio-temporally arranged signaling molecules and external stimuli, cues for cell adhesion, migration, proliferation and differentiation. Faithfully mimicking the in vivo cell microenvironment is a priority for basic cell biology and stem cell therapy. My proposed research in the near term will focus on creating a well-defined biomimetic microenvironment from biomaterials, micro-/nanofabrication and microfluidic approaches and investigate how these external stimuli, in particular, physical cues influence stem cell behavior. Through the mechanistic study with the biomimetic microenvironment, the merits of the physical cues in regulation of stem cell fate will be clarified, thus leading to the development of new biomaterials and biomedical devices. My proposed research in the long term will focus on applying this fundamental understanding, transport phenomena principles, and bioreactor approach to scale up the expansion and differentiation of stem cells for clinical transplantation.

Creation of the biomimetic microenvironment demands advances in polymer nanoengineering and polymer nanomateirals. Our severely limited understanding of structure-property relations in polymers at the nanoscale poses a major obstacle toward rational development of novel materials and processes for fabrication of nanodevices. Only by improving our fundamental understanding of the nanoscale properties of polymers, will we be able to elucidate scientific and engineering principles related to nanoscale structure and processes. My proposed research will focus on developing nanoengineering technologies to generate polymeric nanostructures and advancing experimental tools to probe the thermal, rheological and mechanical responses of the nanoconfined polymers. With the understanding of the properties of nanoconfined polymers, I will manipulate the nanoparticles of desired size, shape, and surface chemistry at three levels, namely particle aggregation/dispersion, 2-D and 3-D particle orientation and interconnection, and functionalization in the matrix for targeted properties. By utilizing a combination of controlled chemistry, controlled morphology, and polymer compounding techniques, a cost-effective, scalable procedure is expected to be developed to engineer functional polymer nanomaterials for biomedical applications as well industrial applications.