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Model polymer system for investigating the generation of hydrogen peroxide and its biological responses during the crosslinking of mussel adhesive moiety

机译:用于研究贻贝粘合部分交联期间研究过氧化氢生成及其生物反应的模型聚合物体系

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摘要

Mussel adhesive moiety, catechol, has been utilized to design a wide variety of biomaterials. However, the biocompatibility and biological responses associated with the byproducts generated during the curing process of catechol has never been characterized. An in situ curable polymer model system, 4-armed polyethylene glycol polymer end-capped with dopamine (PEG-D4), was used to characterize the production of hydrogen peroxide (H2O2) during the oxidative crosslinking of catechol. Although PEG-D4 cured rapidly (under 30 s), catechol continues to polymerize over several hours to form a more densely cross linked network over time. PEG-D4 hydrogels were examined at two different time points; 5 min and 16 h after initiation of crosslinking. Catechol in the 5 min-cured PEG-D4 retained the ability to continue to crosslink and generated an order of magnitude higher H2O2 (40 mu M) over 6 h when compared to 16 h cured samples that ceased to crosslink. H2O2 generated during catechol crosslinking exhibited localized cytotoxicity in culture and upregulated the expression of an antioxidant enzyme, peroxiredoxin 2, in primary dermal and tendon fibroblasts. Subcutaneous implantation study indicated that H2O2 released during oxidative crosslinking of PEG-D4 hydrogel promoted superoxide generation, macrophage recruitment, and M2 macrophage polarization in tissues surrounding the implant. Given the multitude of biological responses associated with H2O2, it is important to monitor and tailor the production of H2O2 generated from catechol-containing biomaterials for a given application.
机译:贻贝粘合剂部分,儿茶酚,已被用于设计各种各样的生物材料。然而,与在儿茶酚的固化过程中产生的副产物相关的生物相容性和生物反应从未被表征。使用多巴胺(PEG-D4)的原位固化聚合物模型系统,用多巴胺(PEG-D4)结束封端,在儿茶酚的氧化交联期间表征过氧化氢(H2O2)的产生。虽然PEG-D4快速固化(30秒以下),但儿茶酚继续聚合几个小时以随着时间的推移形成更密集的交叉连接网络。在两个不同的时间点检查PEG-D4水凝胶;交联后5分钟和16小时。在5分钟固化的PEG-D4中的儿茶酚保留了继续交联并产生超过6小时的数量级,并在6小时内产生的能力,该样品与不交联的16小时。在儿茶酚交联期间产生的H 2 O 2在培养上表现出局部的细胞毒性,并在原发性皮肤和肌腱成纤维细胞中上调抗氧化酶的表达。皮下植入研究表明,在植入物周围的组织中促进过氧化物交联期间释放的H2O2在氧化交联期间促进过氧化物产生,巨噬细胞募集和M2巨噬细胞极化。鉴于与H 2 O 2相关的多种生物反应,重要的是监测和定制由含儿茶酚生物材料产生的H 2 O 2的生产,以用于给定应用。

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