Engineering PEG-based hydrogels to foster efficient endothelial network formation in free-swelling and confined microenvironments.

摘要: Abstract In vitro tissue engineered models are poised to have significant impact on disease modeling and preclinical drug development. Reliable methods induce microvascular networks in such microphysiological systems needed improve the size physiological function of these models. By systematically engineering several physical biomolecular properties cellular microenvironment (including crosslinking density, polymer adhesion ligand concentration, degradability), we establish design principles that describe how synthetic matrix influence vascular morphogenesis modular tunable hydrogels based commercial 8-arm poly (ethylene glycol) (PEG8a) macromers. We apply generate endothelial exhibit consistent morphology throughout depths hydrogel greater than 1 mm. These PEG8a-based relatively high volumetric swelling ratios (>1.5), which limits their utility confined environments as microfluidic devices. To overcome this limitation, mitigate by incorporating a highly functional PEG-grafted alpha-helical (propargyl- l -glutamate) (PPLGgPEG) macromer along with canonical PEG8a gel formation. This platform supports enhanced neutral-swelling environments. Finally, incorporate PEG8a-PPLGgPEG gels into devices demonstrate improved diffusion kinetics network formation situ compared gels.