Development of a Dual Hydrogel Model System for Vascularization

Abstract

Numerous hydrogel-based culture systems are used to create in vitro model for prevascularization. Hydrogels used to induce a microenvironment conducive to microvessel formation are typically soft and fast degradable, but often suffer from maintaining a lasting perfusable channel in vitro. Here, a dual hydrogel system that consists of photo-crosslinkable gelatin methacrylate (GelMA) and polyethylene glycol dimethacrylate (PEGDMA) is reported. GelMA hydrogels present soft and rapidly degradable properties and show microporous structures while PEGDMA is relatively stiff, almost nondegradable in vitro, and less porous. The dual hydrogel system is sequentially photo-crosslinked to construct an endothelial cell (EC)-lined perfusable PEGDMA channel and surrounding GelMA for endothelial vascular networks. Such dual hydrogel system exhibits seamless integration of the stiff PEGDMA channel and the surrounding soft GelMA, and facilitates rapid EC sprouting and extensive microvessel formation from a stable endothelium on the PEGDMA channel into the GelMA. Furthermore, diffusivity of biomolecules in the perfusable dual hydrogel system is affected by both the structural and physicochemical properties of the hydrogel system and the microvascular networks formed in the system. The establishment of the dual hydrogel system for vascularization holds great promise as an in vitro angiogenesis model and prevascularization strategy of large tissue constructs.