Sree Chitra Tirunal Institute for Medical Sciences and Technology, Polymer Science Division, BMT Wing, Thiruvananthapuram 695 012, Kerala State, India.
Dept. of Biomedical Sciences, Creighton University, 2500 California Plaza, Omaha NE68178, USA.
Mater Sci Eng C Mater Biol Appl. 2017 Feb 1;71:100-110. doi: 10.1016/j.msec.2016.09.087. Epub 2016 Sep 30.
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.
炎症和梗死的心脏组织产生的病理性自由基会干扰自然的组织修复机制。非再生心脏组织损伤区域的缺氧微环境会阻碍包括细胞治疗在内的治疗尝试。在这里，我们报告了一种可注射的、细胞相容的、自由基清除的合成水凝胶制剂，用于再生治疗。新的水凝胶（PEAX-P）由 D-木糖醇-富马酸-co-聚已二酸乙二醇-co-PEG 共聚体（PEAX）和 PEG 二丙烯酸酯制备。PEAX-P 水凝胶在平衡溶胀时的初始重量增加 4.9 倍，并保持 100.07kPa 的杨氏模量，这使其适用于心脏应用。PEAX-P 水凝胶即使在 60%的压缩应变下仍保持弹性，这有利于与动态和弹性的天然组织相匹配。PEAX-P 水凝胶可清除 51%DPPH 自由基、40%羟基自由基、41%硝酸盐自由基和 31%的还原力。水凝胶的存在可保护 62%在 LD50 浓度下用应激诱导培养基处理的心肌细胞。共聚体中糖醇的游离羟基基团影响自由基清除。相比之下，PEAX-P 水凝胶基于木糖醇，其清除自由基的特性略低于先前报道的含有更多羟基基团的甘露醇的 PEAM-P 水凝胶。本水凝胶的可能自由基清除机制依赖于与未交联的富马酸键相关的自由π电子、与糖醇/PEG 相关的氢原子以及基质中自由水的自由基稀释。简而言之，目前的 PEAX-P 水凝胶是一种有潜力的用于联合抗氧化和再生治疗的可注射系统。
