Weaver Jessica D, Stabler Cherie L
Department of Biomedical Engineering, College of Engineering, University of Miami, Coral Gables, FL 33146, USA; Diabetes Research Institute, Miller School of Medicine, University of Miami, Miami, FL 33136, USA.
Department of Biomedical Engineering, College of Engineering, University of Miami, Coral Gables, FL 33146, USA; Diabetes Research Institute, Miller School of Medicine, University of Miami, Miami, FL 33136, USA; Department of Surgery, Miller School of Medicine, University of Miami, Miami, FL 33136, USA; Department of Biochemistry and Molecular Biology, Miller School of Medicine, University of Miami, Miami, FL 33136, USA.
Acta Biomater. 2015 Apr;16:136-44. doi: 10.1016/j.actbio.2015.01.017. Epub 2015 Jan 22.
Oxidative stress and the resulting radical by-products cause significant toxicity and graft loss in cellular transplantation. Here, the engineering of an auto-catalytic, antioxidant, self-renewing cerium oxide nanoparticle (CONP)-composite hydrogel is reported. This enzyme-mimetic material ubiquitously scavenges ambient free radicals, with the potential to provide indefinite antioxidant protection. The potential of this system to enhance the protection of encapsulated beta cells was evaluated. Co-incubation of CONPs free in solution with beta cells demonstrated potent cytoprotection from superoxide exposure; however, phagocytosis of the CONPs by the beta cells resulted in cytotoxicity at concentrations as low as 1mM. When CONPs were embedded within alginate hydrogels, the composite hydrogel provided cytoprotection to encapsulated beta cells from free radical attack without cytotoxicity, even up to 10mM. This nanocomposite hydrogel has wide applicability in cellular transplantation, with the unique advantage of localization of these potent antioxidant CONPs and their capacity for sustained, long-term scavenging.
氧化应激及由此产生的自由基副产物在细胞移植中会导致显著的毒性并造成移植物丧失。在此，我们报道了一种自催化、抗氧化、自我更新的氧化铈纳米颗粒（CONP）复合水凝胶的工程设计。这种模拟酶材料能普遍清除周围的自由基，具有提供无限期抗氧化保护的潜力。我们评估了该系统增强对封装的β细胞保护的潜力。溶液中游离的CONP与β细胞共同孵育显示出对超氧化物暴露的强大细胞保护作用；然而，β细胞对CONP的吞噬作用在低至1mM的浓度下就会导致细胞毒性。当CONP嵌入藻酸盐水凝胶中时，复合水凝胶对封装的β细胞提供了免受自由基攻击的细胞保护作用且无细胞毒性，甚至在高达10mM的浓度下也是如此。这种纳米复合水凝胶在细胞移植中具有广泛的适用性，具有这些强大抗氧化CONP定位的独特优势及其持续、长期清除自由基的能力。
