Photodynamic biomaterials for microphysiological tissue engineering

The National Institute of General Medical Sciences awarded $398,464 to the University of Oregon on May 1, 2026, under the Biomedical Research and Research Training program (CFDA 93.859) to develop photoresponsive biomaterials for directing the growth and differentiation of three-dimensional microphysiological tissue systems.

The project focuses on creating smart, light-triggered biomaterials that provide spatial and temporal control over cell growth and differentiation in engineered tissues. The work addresses current limitations in organoid development—including poor reproducibility, heterogeneous morphology, and lack of functional features—by engineering material-agnostic photocleavable crosslinkers that respond to light stimuli. These biomaterials will enable controlled manipulation of matrix properties, porosity, and morphogen gradients to support the development of more complex, biologically relevant tissue environments that transition from two-dimensional cell cultures to functioning three-dimensional organs for personalized medicine applications.

Performance takes place in Eugene, Oregon, with a period of performance extending from May 1, 2026, through March 31, 2031. This is a Project Grant, the standard NIH investigator-initiated research award mechanism.

Abstract

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.