Human Cell‐Derived Matrix Composite Hydrogels with Diverse Composition for Use in Vasculature‐on‐chip Models

Abstract

Microphysiological 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.

Engineering cell-derived extracellular matrix for peripheral nerve regeneration

“…The hydrogel generated by fibroblast-derived ECMs can serve as a biomimetic substrate for vascularization. These suggest their future applications for inducing angiogenesis in tissue injury healing and regenerative contexts [ 110 , 111 ]. The fibroblast-derived ECM hydrogel is also demonstrated to be an excellent pro-regenerative biomaterial with immunomodulatory function, which can significantly alleviate pro-inflammatory cytokine and promote M2-type macrophages, along with significantly elevated vascular endothelial growth factor (VEGF) and basic fibroblast growth factor (bFGF) level [ 112 ].…”