Fiber Reinforcements in Tuning EV Release of Silk Hydrogels

Abstract

The heart has a limited capacity for regeneration following trauma due in part to a low presence of cardiac stem cells. Previous literature has shown that cardiac regeneration may be boosted in the short term by promoting angiogenesis through the addition of certain growth factors present in cardiac stem cells as well as those in endothelial derived extracellular vesicles. To support cardiac angiogenesis more effectively, we propose that an extended-release window of these factors is necessary. The aim of this study is to create a cell-free extracellular vesicle-laden hydrogel system that releases extracellular vesicles over such an extended period (14 days). We went with a casted product; however, 3D extrusion printing may be considered in future research to increase control and resolution of the product, the product being a cardiac patch containing extracellular-vesicle-loaded hydrogels. For this hydrogel system, both gelatine methacryloyl and silk fibroin-based hydrogels were investigated, using lithium phenyl-2,4,6-trimethylbenzoylphosphinate and a combination of riboflavin and sodium persulfate as photocrosslinkers, respectively. The former was used in combination with ultraviolet light, whereas the latter initiated photocrosslinking through visible light. The degradation kinetics, mechanical properties, permeability, and extracellular vesicle release kinetics of our hydrogels were investigated and may be tuned through the varying gel precursor concentration and integration of a supporting melt electrowritten polycaprolactone mesh scaffold featuring a hexagonal structure.