Free radical scavenging injectable hydrogels for regenerative therapy

•Novel injectable hydrogel (PEAX-P) is prepared using D-xylitol-co-fumarate-co-poly ethylene adipate-co-PEG comaromer.•The PEAX-P hydrogel has suitable swelling, mechanical and degradation characterestics for injectable myocardial therapy.•The PEAX-P hydrogel scavenge 51% DPPH radical, 40% hydroxyl radicals and 41% nitrate radicals.•The in vitro studies confirm the protective effect of the present hydrogel on cardiomyoblast cells under oxidative stress.•The free electrons, hydrogen atoms and free water are responsible for the free radical scavenging property of hydrogel.•The present hydrogel is a potential candidate for myocardial regenerative therapy even with hypoxic microenvironment.

Pathological free radicals generated from inflamed and infarcted cardiac tissues interferes natural tissue repair mechanisms. Hypoxic microenvironment at the injured zone of non-regenerating cardiac tissues hinders the therapeutic attempts including cell therapy. Here we report an injectable, cytocompatible, free radical scavenging synthetic hydrogel formulation for regenerative therapy. New hydrogel (PEAX-P) is prepared with D-xylitol-co-fumarate-co-poly ethylene adipate-co-PEG comaromer (PEAX) and PEGDiacrylate. PEAX-P hydrogel swells 4.9 times the initial weight and retains 100.07 kPa Young modulus at equilibrium swelling, which is suitable for cardiac applications. PEAX-P hydrogel retains elastic nature even at 60% compressive strain, which is favorable to fit with the dynamic and elastic natural tissue counterparts. PEAX-P hydrogel scavenges 51% DPPH radical, 40% hydroxyl radicals 41% nitrate radicals with 31% reducing power. The presence of hydrogel protects 62% cardiomyoblast cells treated with stress inducing media at LD 50 concentration. The free hydroxyl groups in sugar alcohols of the comacromer influence the free radical scavenging. Comparatively, PEAX-P hydrogel based on xylitol evinces slightly lower scavenging characteristics than with previously reported PEAM-P hydrogel containing mannitol having more hydroxyl groups. The possible free radical scavenging mechanism of the present hydrogel relies on the free π electrons associated with uncrosslinked fumarate bonds, hydrogen atoms associated with sugar alcohols/PEG and radical dilution by free water in the matrix. Briefly, the present PEAX-P hydrogel is a potential injectable system for combined antioxidant and regenerative therapy.

Graphical abstractInjectable hydrogel with inherent free radical scavenging property for regenerative tissue engineering application.Download high-res image (240KB)Download full-size image