The spatiotemporal control of erosion and molecular release from micropatterned poly(ethylene glycol)-based hydrogel

Hydrogels have been extensively studied as a carrier of various hydrophilic molecular compounds and cells for local delivery and subsequent controlled release. One of key design parameters in the hydrogel assembly is an ability to control spatiotemporal gel degradation, in order to tailor release rates of multiple drugs and also regulate phenotypic activities of co-cultured cells. To achieve this goal, this study presents a simple but innovative implantable, microfabricated hydrogel patch that undergoes micropatterned surface erosion at controlled rates and subsequently discharges two molecular compounds of interests at desired rates. This device was prepared by first fabricating a non-degradable poly(ethylene glycol) dimethacrylate (PEGDMA) hydrogel patch containing micro-pockets of controlled spacing and subsequently filling micro-pockets with a hydrogel of poly(ethylene imine) (PEI) and PEG diacrylate (PEGDA) that was tailored to degrade at controlled rates. Separate incorporation of vascular endothelial growth factor (VEGF)121 and VEGF165, known to orchestrate vascular development, into the PEI-PEGDA gel and PEGDMA hydrogel resulted in enhanced neovascularization at the implantation sites due to bimodal, sequential release of two VEGF isoforms. We believe that the hydrogel patch fabricated in this study will be highly useful to better understand a broad array of complex biological processes and also improve the efficacy of molecular cargos in varied applications.