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A Collagen Based Cryogel Bioscaffold that Generates Oxygen for Islet Transplantation

机译:基于胶原蛋白的低温凝胶生物支架,可为胰岛移植产生氧气。

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The aim of this article is to develop, characterize, and test a novel 3D bioscaffold matrix that can accommodate pancreatic islets and provide them with a continuous, controlled, and steady source of oxygen to prevent hypoxia-induced damage following transplantation. Hence, a collagen-based cryogel bioscaffold that incorporates calcium peroxide (CPO) into its matrix is made. The optimal concentration of CPO integrated into bioscaffolds is 0.25 wt% and this generates oxygen at 0.21 +/- 0.02 x 10(-3) m day(-1) (day 1), 0.19 +/- 0.01 x 10(-3) m day(-1) (day 6), 0.13 +/- 0.03 x 10(-3) m d(-1) (day 14), and 0.14 +/- 0.02 x 10(-3) m d(-1) (day 21). Accordingly, islets seeded into cryogel-CPO bioscaffolds have a significantly higher viability and function compared to islets seeded into cryogel alone bioscaffolds; these findings are supported by data from quantitative computational modeling. When syngeneic islets are transplanted into the epididymal fat pad (EFP) of diabetic mice, the cryogel-0.25 wt%CPO bioscaffold improves islet function with diabetic animals re-establishing glycemic control. Mice transplanted with cryogel-0.25 wt%CPO bioscaffolds show faster responses to intraperitoneal glucose injections and have a higher level of insulin content in their EFP compared to those transplanted with islets alone (P < 0.05). The novel oxygen-generating bioscaffold (i.e., cryogel-0.25 wt%CPO) therefore provides a biostable and biocompatible 3D microenvironment for islets which can facilitate islet survival and function at extra-hepatic sites of transplantation.
机译:本文的目的是开发,表征和测试新型3D生物支架基质,该基质可容纳胰岛,并为它们提供连续,受控和稳定的氧气来源,以防止移植后低氧引起的损伤。因此,制备了将过氧化钙(CPO)结合到其基质中的基于胶原的冷冻凝胶生物支架。整合到生物支架中的CPO的最佳浓度为0.25 wt%,这会在第(-1)天(-1),0.19 +/- 0.01 x 10(-3)的0.21 +/- 0.02 x 10(-3)m天产生氧气m天(-1)(第6天),0.13 +/- 0.03 x 10(-3)md(-1)(第14天)和0.14 +/- 0.02 x 10(-3)md(-1)(第21天)。因此,与仅接种到冷冻凝胶生物支架中的胰岛相比,接种到冷冻凝胶-CPO生物支架中的胰岛具有明显更高的生存力和功能。这些发现得到了定量计算建模数据的支持。当将同基因胰岛移植到糖尿病小鼠的附睾脂肪垫(EFP)中时,cryogel-0.25 wt%CPO生物支架可改善糖尿病动物的胰岛功能,从而重新建立血糖控制。与单独胰岛移植的小鼠相比,用冷冻凝胶-0.25 wt%CPO生物支架移植的小鼠对腹腔内葡萄糖注射的反应更快,并且其EFP中的胰岛素含量更高(P <0.05)。因此,新型的产生氧气的生物支架(即cryogel-0.25wt%CPO)为胰岛提供了生物稳定和生物相容的3D微环境,其可以促进胰岛的存活和在肝外移植部位的功能。

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