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High oxygen preservation hydrogels to augment cell survival under hypoxic condition

机译:高氧保存水凝胶在缺氧条件下增加细胞存活

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Cell therapy is a promising approach for ischemic tissue regeneration. However, high death rate of delivered cells under low oxygen condition, and poor cell retention in tissues largely limit the therapeutic efficacy. Using cell carriers with high oxygen preservation has potential to improve cell survival. To increase cell retention, cell carriers that can quickly solidify at 37 degrees C so as to efficiently immobilize the carriers and cells in the tissues are necessary. Yet there lacks cell carriers with these combined properties. In this work, we have developed a family of high oxygen preservation and fast gelation hydrogels based on N-isopropylacrylamide (NIPAAm) copolymers. The hydrogels were synthesized by reversible addition-fragmentation chain transfer (RAFT) polymerization of NIPAAm, acrylate-oligolactide (AOLA), 2-hydroxyethyl methacrylate (HEMA), and methacrylate-poly(ethylene glycol)-perfluorooctane (MAPEGPFC). The hydrogel solutions exhibited sol-gel temperatures around room temperature and were flowable and injectable at 4 degrees C. They can quickly solidify (<= 6 s) at 37 degrees C to form flexible gels. These hydrogels lost 9.4 similar to 29.4% of their mass after incubation in Dulbecco's Phosphate-Buffered Saline (DPBS) for 4 weeks. The hydrogels exhibited a greater oxygen partial pressure than DPBS after being transferred from a 21% O-2 condition to a 1% O-2 condition. When bone marrow mesenchymal stem cells (MSCs) were encapsulated in the hydrogels and cultured under 1% O-2, the cells survived and proliferated during the 14-day culture period. In contrast, the cells experienced extensive death in the control hydrogel that had low oxygen preservation capability. The hydrogels possessed excellent biocompatibility. The final degradation products did not provoke cell death even when the concentration was as high as 15 mg/ml, and the hydrogel implantation did not induce substantial inflammation. These hydrogels are promising as cell carriers for cell transplantation into ischemic tissues.
机译:细胞疗法是缺血组织再生的有希望的方法。然而,低氧气状况下递送细胞的高死亡率,并且组织中的细胞滞留差在很大程度上限制了治疗效果。使用具有高氧保存的细胞载体具有改善细胞存活的可能性。为了增加细胞保留,可以在37℃下快速固化的细胞载体,以便有效地固定组织中的载体和细胞。然而,缺乏具有这些组合性质的细胞载体。在这项工作中,我们开发了一种基于N-异丙基丙烯酰胺(NIPAAM)共聚物的高氧保存和快速凝胶水凝胶。通过可逆添加 - 丙烯酸盐碎片链转移(RAFT)聚合,丙烯酸酯 - 寡烷烃(AOLA),2-羟乙基甲酸乙酯(HEMA)和甲基丙烯酸酯 - 聚(乙二醇)-perfluoroOcordane(MapegPFC)来合成水凝胶。水凝胶溶液在室温下显示溶胶 - 凝胶温度,并且在4℃下可流动和注射。它们可以在37℃下快速固化(<= 6s)以形成柔性凝胶。这些水凝胶损失了9.4,在Dulbecco的磷酸盐缓冲盐水(DPBS)孵育后,其含量的29.4%。在将从21%O-2条件下转移至1%O-2条件后,水凝胶表现出比DPB更大的氧分压。当骨髓间充质干细胞(MSCs)包封在水凝胶中并在1%O-2下培养时,细胞在14天培养期间存活并增殖。相反,细胞在具有低氧保存能力的对照水凝胶中经历了广泛的死亡。水凝胶具有优异的生物相容性。即使当浓度高达15mg / ml时,最终的降解产物也没有引发细胞死亡,并且水凝胶植入没有诱导显着炎症。这些水凝胶是有前途的细胞载体,用于细胞移植到缺血组织中。

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