Microfabricated bioactive hydrogel platform as in vitro models to understand the mechanobiology of cell-matrix interaction in human tissue

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In vitro models are valuable tools to study human tissue development and aging; however, simple-to-use in vitro models that recapitulate extracellular microenvironmental signals are yet to be developed. The proposed research program aims to apply microfabrication and bioactive hydrogel to create a biomimicking platform for mechanistic studies of cell-matrix interactions in corneal and vascular tissues, in both the healthy microenvironment and age- or stress-remodeled microenvironment. Cell-matrix responses are complex and cell responses are also influenced by the physical and chemical microenvironment. Physical cues in the microenvironment, such as rigidity and topography, have been shown to significantly affect cell behaviours. The overarching hypothesis of this program is that the mechanobiology of the extracellular microenvironment could affect cell behaviors and cell functions, in turn affecting the functionality of cells. Our group has been studying the mechanobiology of cell-material interactions for tissue engineering applications. Using microfabrication technologies, we have developed various techniques for patterning hydrogel in 3D non-planar surfaces and have demonstrated the feasibility of applying these platforms to develop in vitro tissue models. The key approach of the proposed program is to use microfabrication techniques and hydrogel to build biomaterial platforms to recapitulate biomimicking microenvironments. The main objectives are: O1 to develop a 2D in vitro model with biomimicking topographical and mechanical properties of corneal Descemet's membrane (DM) with microfabrication of hydrogel, to study cell migration, cell-cell and cell-matrix interactions in healthy and age-remodeled corneal microenvironment; O2 to develop a 3D platform with integrated biomimicking topography, mechanical properties and mechanical stimulation, to study cell responses in complex vascular geometry and in aging vasculature, and O3 to develop a 2D in vitro model with biomimicking mechanical properties with external mechanical stimulation to understand the role of mechanical stimuli in eye-rubbing. This research program will enable the development of in vitro models using engineering platforms as tools for aging research and allow for significant new understanding of the fundamental science in cell signalling and biomechanical factors that affect the success of potential interventions. The program will also provide economic impact by influencing the design of new products and developing concepts and technologies that can be patented. The in vitro model may lead to new devices applicable in biomedical engineering areas, with eventual applications in drug-screening and interventions in aging. In addition, the program will provide a pool of highly trained scientists and engineers for the fields of biotechnology, biomedical engineering, materials science and pharmaceutical industry.