Niche-inspired Biomaterials to Build Human In Vitro Tissue Models

Speaker

Victor Hernandez-Gordillo, Ph.D.
Postdoctoral Research Associate
Massachusetts Institute of Technology

Abstract

Humanized animal models and immortalized cell lines usually fail to recapitulate full tissue architecture and function. New technologies able to incorporate multiple cell types with micro-architecture, and nearphysiological tissue functions are needed to solve this limitation. These new technologies require a supportive matrix that can be tuned to accommodate various cell types and configurations. Inspired by integrin expressed in the native tissue, I have established design strategies to create fully synthetic matrices with tunable biomolecular and biophysical properties to engage integrins expressed by the target cells. The local biophysical presentation of the cues, rather than bulk mechanical properties, appears to be the dominant parameter governing stromal and epithelial cell proliferation in the synthetic matrix. Using organoids as an example, I identified an a2b1 integrinbinding peptide as a critical component of the synthetic matrix that supports human duodenal colon and endometrial organoid propagation. We show that organoids emerge from single cells, retain their proliferative capacity, are functionally responsive to basolateral stimulation, and have correct apicobasal polarity upon induction of differentiation.