Meng Hao, Li Yuting, Faust Madeline, Konst Shari, Lee Bruce P
Department of Biomedical Engineering, Michigan Technological University, Houghton, MI 49931, USA.
Department of Chemistry, Michigan Technological University, Houghton, MI 49931, USA.
Acta Biomater. 2015 Apr;17:160-9. doi: 10.1016/j.actbio.2015.02.002. Epub 2015 Feb 10.
To decouple the extracellular oxidative toxicity of catechol adhesive moiety from its intracellular non-oxidative toxicity, dopamine was chemically bound to a non-degradable polyacrylamide hydrogel through photo-initiated polymerization of dopamine methacrylamide (DMA) with acrylamide monomers. Network-bound dopamine released cytotoxic levels of H2O2 when its catechol side chain oxidized to quinone. Introduction of catalase at a concentration as low as 7.5 U/mL counteracted the cytotoxic effect of H2O2 and enhanced the viability and proliferation rate of fibroblasts. These results indicated that H2O2 generation is one of the main contributors to the cytotoxicity of dopamine in culture. Additionally, catalase is a potentially useful supplement to suppress the elevated oxidative stress found in typical culture conditions and can more accurately evaluate the biocompatibility of mussel-mimetic biomaterials. The release of H2O2 also induced a higher foreign body reaction to catechol-modified hydrogel when it was implanted subcutaneously in rat. Given that H2O2 has a multitude of biological effects, both beneficiary and deleterious, regulation of H2O2 production from catechol-containing biomaterials is necessary to optimize the performance of these materials for a desired application.
为了将儿茶酚粘附部分的细胞外氧化毒性与其细胞内非氧化毒性分离,通过多巴胺甲基丙烯酰胺(DMA)与丙烯酰胺单体的光引发聚合反应,将多巴胺化学结合到不可降解的聚丙烯酰胺水凝胶上。当网络结合的多巴胺的儿茶酚侧链氧化为醌时,会释放出具有细胞毒性水平的过氧化氢(H2O2)。以低至7.5 U/mL的浓度引入过氧化氢酶可抵消H2O2的细胞毒性作用,并提高成纤维细胞的活力和增殖率。这些结果表明,H2O2的产生是多巴胺在培养物中细胞毒性的主要原因之一。此外,过氧化氢酶是一种潜在有用的补充剂,可抑制典型培养条件下发现的氧化应激升高,并能更准确地评估仿贻贝生物材料的生物相容性。当儿茶酚修饰的水凝胶皮下植入大鼠体内时,H2O2的释放还会引发对其更高的异物反应。鉴于H2O2具有多种有益和有害的生物学效应,调节含儿茶酚生物材料中H2O2的产生对于优化这些材料在所需应用中的性能是必要的。