Encapsulation of cell-adhesive RGD peptides into a polymeric physical hydrogel to prevent postoperative tissue adhesion.
Encapsulation of cell-adhesive RGD peptides into a polymeric physical hydrogel to prevent postoperative tissue adhesion.
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DOI：
10.1002/jbm.b.32728
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发表时间：
2012-08
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影响因子：
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通讯作者：
Zheng Zhang;Jian Ni;Liang Chen;Lin Yu;Jianwei Xu;Jiandong Ding
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文献类型：
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作者：
Zheng Zhang;Jian Ni;Liang Chen;Lin Yu;Jianwei Xu;Jiandong Ding
含有精氨酸-甘氨酸-天冬氨酸（RGD）序列的肽是一种著名的粘附分子，它能特异性地与细胞膜上的整合素结合，在组织工程中与固体基质连接或在靶向递送中与纳米颗粒连接后，通常被用于增强细胞粘附。然而，本文揭示，游离的RGD肽可以通过阻断细胞与屏障装置表面之间的粘着斑来帮助防止组织粘附。为了避免肽溶液直接注射后的快速肽损失，我们采用由可生物降解的嵌段共聚物聚（ε-己内酯-共-丙交酯）-聚（乙二醇）-聚（ε-己内酯-共-丙交酯）（PCLA-PEG-PCLA）组成的热敏可注射水凝胶来包封环（-RGDfK-）肽。在体外可持续释放一周。采用兔肠壁缺损和肠磨损模型，观察其体内抗粘连效果。它揭示了在负载RGD的PCLA-PEG-PCLA水凝胶组中术后腹膜粘连的显著减少。我们通过两种效果的组合来解释这种优异的功效：首先，我们的水凝胶提供物理屏障以防止受伤的腹壁和盲肠之间的粘连;其次，从水凝胶释放的作为整联蛋白阻断剂的RGD分子有助于抗粘连。
Peptides containing the sequence of arginine-glycine-aspartate (RGD), a famous adhesion moiety, can specifically conjugate integrins in cell membranes, and are usually applied to enhance cell adhesion after linking to solid substrates in tissue engineering or to nanoparticles in targeting delivery. This paper reveals, however, that free RGD peptides can assist in preventing tissue adhesion by blocking focal adhesion between cells and surfaces of barrier devices. In order to avoid a rapid peptide loss after straightforward injection of a peptide solution, we employed a thermosensitive injectable hydrogel composed of a biodegradable block copolymer poly(ε-caprolactone-co-lactide)-poly(ethylene glycol)-poly(ε-caprolactone-co-lactide) (PCLA-PEG-PCLA) to encapsulate peptides cyclo(-RGDfK-). A sustainable release for one week was achieved in vitro. The rabbit model of sidewall defect and bowel abrasion was selected to examine the in vivo anti-adhesion efficacy. It reveals a significant reduction of postoperative peritoneal adhesion in the group of RGD-loaded PCLA-PEG-PCLA hydrogels. We interpret this excellent efficacy by the combination of two effects: first, our hydrogel affords a physical barrier to prevent adhesion between injured abdominal wall and cecum; second, the RGD molecules as integrin blockers released from the hydrogel assist the anti-adhesion.