title: Free radical scavenging injectable hydrogels for regenerative therapy.
abstract: 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 100.07kPa 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.
authors.affiliation: Sree Chitra Tirunal Institute for Medical Sciences and Technology, Polymer Science Division, BMT Wing, Thiruvananthapuram 695 012, Kerala State, India.
authors.forename: Remya
authors.initials: R
authors.lastname: Komeri
authors.affiliation: Dept. of Biomedical Sciences, Creighton University, 2500 California Plaza, Omaha NE68178, USA.
authors.forename: Finosh Gnanaprakasam
authors.initials: FG
authors.lastname: Thankam
authors.affiliation: Sree Chitra Tirunal Institute for Medical Sciences and Technology, Polymer Science Division, BMT Wing, Thiruvananthapuram 695 012, Kerala State, India. Electronic address: mjayabalan52@gmail.com.
authors.forename: Jayabalan
authors.initials: J
authors.lastname: Muthu
mesh_terms: D000818:Animals; D002460:Cell Line; D016166:Free Radical Scavengers / Q000138:chemical synthesis / Q000737:chemistry / Q000493:pharmacokinetics / Q000494:pharmacology; D020100:Hydrogels / Q000138:chemical synthesis / Q000737:chemistry / Q000493:pharmacokinetics / Q000494:pharmacology; D032386:Myoblasts, Cardiac / Q000166:cytology / Q000378:metabolism*; D051381:Rats; D044968:Regenerative Medicine / Q000379:methods*
chemical_list: D016166:Free Radical Scavengers; D020100:Hydrogels
keywords: Antioxidant; Free radical scavenging; Injectable hydrogel; Pathological free radicals; Regenerative therapy