Affiliation:
1. The Joint Department of Biomedical Engineering University of North Carolina at Chapel Hill and North Carolina State University 10010 Mary Ellen Jones Building, 116 Manning Drive Chapel Hill NC 27514 USA
2. Curriculum in Genetics and Molecular Biology University of North Carolina at Chapel Hill School of Medicine 130 Mason Farm Road Chapel Hill Carolina NC 27599 USA
3. Department of Cell Biology and Physiology University of North Carolina at Chapel Hill School of Medicine 111 Mason Farm Road Chapel Hill Carolina NC 27599 USA
Abstract
AbstractMicrophysiological and organ‐on‐chip platforms seek to address critical gaps in human disease models and drug development that underlie poor rates of clinical success for novel interventions. While the fabrication technology and model cells used to synthesize organs‐on‐chip have advanced considerably, most platforms rely on animal‐derived or synthetic extracellular matrix as a cell substrate, limiting mimicry of human physiology and precluding use in modeling diseases in which matrix dynamics play a role in pathogenesis. Here, the development of human cell‐derived matrix (hCDM) composite hydrogels for use in 3D microphysiologic models of the vasculature is reported. hCDM composite hydrogels are derived from human donor fibroblasts and maintain a complex milieu of basement membrane, proteoglycans, and nonfibrillar matrix components. The use of hCDM composite hydrogels as 2D and 3D cell culture substrates is demonstrated, and hCDM composite hydrogels are patterned to form engineered human microvessels. Interestingly, hCDM composite hydrogels are enriched in proteins associated with vascular morphogenesis as determined by mass spectrometry, and functional analysis demonstrates proangiogenic signatures in human endothelial cells cultured in these hydrogels. In conclusion, this study suggests that human donor‐derived hCDM composite hydrogels could address technical gaps in human organs‐on‐chip development and serve as substrates to promote vascularization.
Funder
American Heart Association
National Science Foundation
National Heart, Lung, and Blood Institute
National Institute of General Medical Sciences
Cited by
3 articles.
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