Multifunctional pancreatic islet encapsulation barriers achieved via multilayer PEG hydrogels
Multifunctional pancreatic islet encapsulation barriers achieved via multilayer PEG hydrogels
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DOI：
10.3727/000000007783472336
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发表时间：
2007-01-01
影响因子：
3.3
通讯作者：
Anseth, Kristi S.
中科院分区：
文献类型：
--
作者：
Weber, Laney M.;Cheung, Charles Y.;Anseth, Kristi S.
成功的胰岛封装屏障的不同要求表明，为封装细胞和宿主细胞提供不同功能的屏障系统的好处。最初，多功能水凝胶是通过 PEG 水凝胶层的顺序光聚合合成的，每个水凝胶层具有不同的独立功能。通过对每个水凝胶层内不同的包埋抗体进行免疫染色，证实了实现局部生物功能的能力。然后评估宏观封装在两层水凝胶构建体内部凝胶内的鼠胰岛的存活率。在培养 28 天的多层水凝胶中观察到封装胰岛存活和功能的维持。此外，含有细胞基质部分的胰岛内部 PEG 凝胶层与 100 μg/ml 层粘连蛋白或层粘连蛋白中发现的 5 mM 粘附肽 IKVAV 进行功能化，导致封装胰岛的胰岛素分泌增加，类似于没有外部水凝胶层的凝胶。最后，通过细胞接种实验，证明了未修饰的外部 PEG 层能够防止非封装成纤维细胞与内部 PEG 层内截留的 ECM 成分之间的相互作用，从而防止附着。总之，所呈现的结果支持多层水凝胶用作多功能胰岛封装屏障的潜力，其提供局部生物活性胰岛微环境，同时向宿主环境提供惰性、免疫保护性外表面，以最大限度地减少移植物与宿主的相互作用。
The diverse requirements for a successful islet encapsulation barrier suggest the benefit of a barrier system that presents differing functionalities to encapsulated cells and host cells. Initially, multifunctional hydrogels were synthesized via the sequential photopolymerization of PEG hydrogel layers, each with different isolated functionalities. The ability to achieve localized biological functionalities was confirmed by immunostaining of different entrapped antibodies within each hydrogel layer. Survival of murine islets macroencapsulated within the interior gel of two-layer hydrogel constructs was then assessed. Maintenance of encapsulated islet survival and function was observed within multilayer hydrogels over 28 days in culture. Additionally, the functionalization of the islet-containing interior PEG gel layer with cell-matrix moieties, with either 100 mu g/ml laminin or 5 mM of the adhesive peptide IKVAV found in laminin, resulted in increased insulin secretion from encapsulated islets similar to that in gels without an exterior hydrogel layer. Finally, through cell seeding experiments, the ability of an unmodified, exterior PEG layer to prevent interactions, and thus attachment, between nonencapsulated fibroblasts and entrapped ECM components within the interior PEG layer was demonstrated. Together the presented results support the potential of multilayer hydrogels for use as multifunctional islet encapsulation barriers that provide a localized biologically active islet microenvironment, while presenting an inert, immunoprotective exterior surface to the host environment, to minimize graft-host interactions.