Constructing and characterizing 4D tissue models
Seminar with Michael Blatchley, researcher in chemical and biological engineering, University of Colorado-Boulder
Meeting ID: 951 4202 1459
Engineered 4D tissue constructs are uniquely promising benchtop models, owing to their capacity to mimic key architectural and compositional metrics of their in vivo counterparts in a highly controllable manner. In the short term, these models have potential for studies in fundamental biology, disease modeling, personalized medicine, and drug screening, with long term possibilities in constructing patient-specific, transplantable tissues. Physiologically relevant 4D tissue models can overcome limitations associated with oversimplified 2D human cell culture, as well as the ethical and species mismatch issues pervasive with animal studies. A major focus in the development of these more biomimetic models has been on the presentation of soluble biochemical cues that activate or inhibit signaling pathways leading to cellular self-organization, resulting in lab-grown constructs that mimic many features of native tissue.
Fewer studies have sought to understand the role of other extracellular niche cues, and the dynamics of those cues, on cell signaling and morphogenesis. For studies focused on these extracellular cues, hydrogels are particularly well suited as biomaterials that can match niche specific properties, including matrix mechanics, integrin binding specificity, degradability, and oxygen tension. The initial conditions of hydrogels can be engineered to optimize cell survival and growth, while dynamic boundary conditions can be regulated by phototunable alterations to the hydrogel properties to guide cell behavior with spatiotemporal precision and match the dynamics of the native microenvironment.
In this talk, I’ll discuss specific applications in using hydrogels:
- to model the vascular regenerative niche by controlling oxygen tension and matrix mechanics,
- for expansion microscopy to characterize tissue-specific niche properties of organoids, and
- to tune the matrix mechanics at precise points in space and time to direct intestinal organoid morphogenesis.