Associate Professor University of Delaware Landenberg, Pennsylvania, United States
Introduction: Many diseases either directly affect the cardiovascular system, hypertension and inflammation for example, or utilize the cardio and/or lymphatic vasculature during disease progression, cancer metastasis for example. While diseases that affect or utilize cardiovasculature can be studied in both human and animal models, high-resolution temporal imaging of cellular and subcellular events during these processes is often challenging due to the resolution limitations of existing in vivo imaging modalities. Accordingly, the ability to model these processes using engineered vasculature in fluidized, in vitro devices offers the opportunity to begin forming a better understanding of the cellular and molecular mechanisms occurring. Toward this goal, I will discuss two biofabrication techniques (wire-templating, laser-induced hydrogel degradation) to generate simple, three-dimensional microvasculature embedded in synthetic (poly(ethylene glycol)-based) or natural (collagen, fibrin) hydrogels. I will also discuss characterization of these vessels in both basal and inflamed conditions and fabrication of multicellular structures. The implementation of these devices to form a better understanding of the cellular and molecular mechanisms that facilitate extravasation of circulating tumor cells during breast cancer metastasis and the potential role of pathological hemodynamics in dementia will be briefly discussed.
Materials and
Methods: Wire-templating and laser-induced hydrogel degradation of low-swelling ratio synthetic and natural hydrogels, as well as high-swelling synthetic hydrogels will be discussed. Thorough characterization of endothelial cells and their response to inflammation will also be discussed. The ability to pressurize these vessels and characterize vessel wall strain and strain propagation into the surrounding tissue via finite element modeling will be discussed.
Results, Conclusions, and Discussions: We have demonstrated that these biofabrication approaches generate microvessels with in vivo-like properties with regards to permeability and response to inflammatory molecules. We have also developed methods for producing these biomimetic microvessels in very high-swelling hydrogels which paves the way for utilizing perfusable microsystems to unravel the role of hemodynamics in various pathological processes.
.jpg "John H. Slater, PhD (he/him/his) photo")