CBE & MSE Seminar: Engineering Cell Niches with Biomaterial Topographies for Tissue Engineering Applications

Abstract: Stem cells respond to both physical and biochemical changes in their stem cell niche. An ideal scaffold for tissue engineering application should mimic the microenvironment for natural tissue development and present the appropriate biochemical and topographical cues in a spatially controlled manner. Studies have shown that physical forces from the substrate topography play a role in stem cell proliferation, migration and cell fate determination. Our research group is interested in studying the interactions of adult and pluripotent stem cells with nanotopography, the mechanism of the topography-induced cell behavior and how to apply this knowledge to direct stem cell differentiation for tissue engineering applications. In this presentation, nanotopography regulation on adult stem cells and pluripotent stem cells (PSCs) will be presented as examples of applying nanotopography in stem cell regulation.

A Multi ARChitectural (MARC) chip containing fields of various geometries and size was developed to investigate the influence of topography geometry on differentiation. We demonstrated that the application of anisotropic topography enhanced neuronal differentiation. In an attempt to understand the sensing mechanisms for nanotopography, we investigated the roles of focal adhesion signaling and cytoskeletal contractility in topography-induced differentiation. We showed that the nanotopography-induced differentiation mesenchymal stem cells (hMSCs) is modulated through cell mechanotransduction by the integrin-activated focal adhesion kinase (FAK). In addition, our mechanistic study in hMSCs and hPSCs confirmed that the regulation was dependent upon actomyosin contractility, suggesting a direct force-dependent mechanism. Using a 3D traction force system to study the cell contractility on anisotropic grating topography, we showed that the elongated cells on grating substrates exert anisotropic traction stresses, in the direction parallel to the grating direction. Our study of temporal presentation of topography during hPSC neuronal differentiation showed that the topography contact during the differentiation period is necessary and significant for topography-induced differentiation.

Examples of nanotopography-modulation on cell behaviors for tissue-engineering applications will be discussed in the last part of the presentation.

Bio: Evelyn Yim received her doctorate in biomedical engineering at Johns Hopkins University before undergoing her postdoctoral training at Johns Hopkins School of Medicine and in the Department of Biomedical Engineering at Duke University. Between 2007 and 2015, Yim worked in Singapore, where she held a joint appointment with the National University of Singapore as faculty in the Departments of Biomedical Engineering and Surgery, and the Mechanobiology Institute Singapore as a principle investigator studying how chemical and biomechanical cues influence stem cell behavior. 

Yim joined the Department of Chemical Engineering at the University of Waterloo in 2016. Experienced with nanofabrication technologies and stem cell culture, Yim and her group are interested in applying the knowledge of biomaterial-stem cell interaction to direct stem cell differentiation and tissue regeneration for vascular and corneal tissue engineering.

Host: Professor Albert Yee