It is now well established that ECM-based cues play a critical role in modulating various cellular functions such as adhesion, differentiation, and functional tissue formation, though the underlying mechanisms remain unknown. In an effort to dissect the role of biophysical and biochemical cues of the ECM in directing stem cell commitment, we are developing artificial ECMs recapitulating various physicochemical cues of the native tissue. Examples include biomineralized matrices for osteogenic differentiation of stem cells and smart biomaterials as bioactuators for stem cell culture. Additionally, we are also interested in designing synthetic materials emulating various attributes of biological systems such as sensitivity, self-organization, and self-healing. One of our efforts centers on manipulating inter- and intramolecular forces to form structures with intriguing functions and properties. We have a number of ongoing projects. (i) Designing biomaterials to understand the role of interfacial properties on cell adhesion, migration, and differentiation (Ayala et al., Engineering the cell-material interface for controlling stem cell adhesion, migration, and differentiation". Biomaterials, 32:3700-3711, (2011)).
(ii) Engineering cell-matrix interface to promote self-renewal of hESCs and iPSCs (Chang CW et al., "Engineering Cell-Material Interfaces for Long-term Expansion of Pluripotent Stem Cells." Biomaterials S0142-9612(12):1141-1146 (2012).(iii) Employing principles of biomineralization of create synthetic matrices recapitulating mineral environment of the bone tissue. These biomimetic materials function as a platform to study osteogenic differentiation of stem cells (Phadke et al., Mineralized Synthetic Matrices as an Instructive Microenvironment for Osteogenic Differentiation of Human Mesenchymal Stem Cels". Macromol. BioSci. 12(8):1022-1032 (2012)) and understanding how biomaterials can influence stem cell commitment through metabolic pathway (Yuru et al., submitted).
We are also investigating how these materials could be used activate endogenous cells to promote bone healing (Phadke et al., Effect of Scaffold Microarchitecture on Osteogenic Differentiation of Human Mesenchymal Stem Cells" European Cells and Materials. ECM 25:114-129 (2013)). (iv) Development of multi-functional, bioactuating materials for cell culture. We are interested in designing the next generation of biomaterials that are multifunctional and possess actuating potential to provide different physicochemical cues to the encapsulated cells. These biomaterials are developed based on the ability of certain hydrogels to undergo volume phase transition responding to subtle changes in an environmental stimulus. One of such system, electro-chemo-mechanical matrix, developed to exhibit on-off bending and directionality was found to promote chondrogenic differentiation of hMSCs (Lim et al.). (v) Smart materials with self-healing function. One of the unique characteristics of biological tissue is their ability to heal. In an effort to mimic this biological function in synthetic materials we are developing new design principles to create crosslinked hydrogels exhibiting self-healing potential.