Photodynamic Biomaterials for Microphysiological Tissue Engineering

About This Grant

PROJECT SUMMARY The leap from 2D cell culture to functioning 3D organs is one of the biggest opportunities in developmental biology and patient-specific tissues/personalized medicine. Our current method for growing complex 3D microphysiological systems (MPSs) relies heavily on the innate biology of adult induced pluripotent stem cells (iPSCs) to differentiate into organ-specific cell types, gently guided by the addition of soluble morphogens that direct differentiation. Unfortunately, the result of such a biology-driven, uncontrolled process are small organoids that lack reproducibility, specificity in cell type composition, and functionality. They exhibit uncontrolled size, heterogeneity of shape, and lack appropriate vascular, immune, neural components and organ-specific morphological features. To address this challenge, we need “smart”, stimulus responsive systems that offer control over various facets of cell growth and differentiation. This program’s goal is to develop smart, photoresponsive biomaterials to control and direct biological events, which will allow the study of more complex tissue environments and development of biologically relevant microphysiological systems. Directing the growth of 3D tissues requires spatial and temporal control across multiple factors, including matrix density, porosity, and gradients of soluble morphogens. Smart biomaterials that incorporate a light-triggered response offer the best level of control over these factors. Current photocleavable chemistries (chromophores that undergo bond cleavage when a photon is absorbed) are synthetically challenging to access, which has stalled their application across diverse material supports. We need a simple, readily modified chromophore that is material-agnostic for ready translation into any material support needed across this diverse field. Our unique approach to develop material agnostic photocleavable crosslinkers builds upon the powerful photochemistry and ready synthesis of ruthenium polypyridyl complexes. We have already shown excellent biocompatibility, synthetic flexibility with multiple reactive chemistries, and excellent photophysical properties of Ru complexes in biomaterial systems. This program will leverage this chemistry and demonstrate its broad application across multiple systems that provide spatiotemporal control of physical and biological cues in two main projects: 1) probing pathophysiological systems through control of the physical extracellular environment, and 2) directing cell attachment and growth through spatiotemporal patterning of biochemical cues within a material.