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基于 Arg-Glyc-Asp(RGD)肽功能化细胞化固体胶原支架的心肌梗死的可能治疗方法。

Possible Treatment of Myocardial Infarct Based on Tissue Engineering Using a Cellularized Solid Collagen Scaffold Functionalized with Arg-Glyc-Asp (RGD) Peptide.

机构信息

Thoracic Surgery Department, Cochin Hospital, APHP Centre, University of Paris, 75014 Paris, France.

Department of Thoracic Surgery, University Hospital Strasbourg, 67000 Strasbourg, France.

出版信息

Int J Mol Sci. 2021 Nov 22;22(22):12563. doi: 10.3390/ijms222212563.

Abstract

Currently, the clinical impact of cell therapy after a myocardial infarction (MI) is limited by low cell engraftment due to low cell retention, cell death in inflammatory and poor angiogenic infarcted areas, secondary migration. Cells interact with their microenvironment through integrin mechanoreceptors that control their survival/apoptosis/differentiation/migration and proliferation. The association of cells with a three-dimensional material may be a way to improve interactions with their integrins, and thus outcomes, especially if preparations are epicardially applied. In this review, we will focus on the rationale for using collagen as a polymer backbone for tissue engineering of a contractile tissue. Contractilities are reported for natural but not synthetic polymers and for naturals only for: collagen/gelatin/decellularized-tissue/fibrin/Matrigel™ and for different material states: hydrogels/gels/solids. To achieve a thick/long-term contractile tissue and for cell transfer, solid porous compliant scaffolds are superior to hydrogels or gels. Classical methods to produce solid scaffolds: electrospinning/freeze-drying/3D-printing/solvent-casting and methods to reinforce and/or maintain scaffold properties by reticulations are reported. We also highlight the possibility of improving integrin interaction between cells and their associated collagen by its functionalizing with the RGD-peptide. Using a contractile patch that can be applied epicardially may be a way of improving ventricular remodeling and limiting secondary cell migration.

摘要

目前,由于细胞保留率低、炎症和血管生成不良的梗死区细胞死亡、继发性迁移等原因,细胞疗法在心肌梗死后的临床效果有限。细胞通过整合素机械感受器与其微环境相互作用,控制其存活/凋亡/分化/迁移和增殖。细胞与三维材料的结合可能是改善与整合素相互作用的一种方法,从而改善治疗效果,尤其是如果将制剂应用于心外膜。在这篇综述中,我们将重点讨论使用胶原蛋白作为聚合物骨架用于可收缩组织工程的基本原理。已经报道了天然聚合物而非合成聚合物的收缩性,并且仅报道了天然聚合物的收缩性:胶原蛋白/明胶/去细胞组织/纤维蛋白/Matrigel™,以及不同的材料状态:水凝胶/凝胶/固体。为了获得厚的/长期的可收缩组织和细胞转移,固体多孔顺应性支架优于水凝胶或凝胶。生产固体支架的经典方法:静电纺丝/冷冻干燥/3D 打印/溶剂浇铸和通过交联增强和/或保持支架性能的方法都有报道。我们还强调了通过 RGD 肽对胶原蛋白进行功能化,从而改善细胞与其相关胶原蛋白之间的整合素相互作用的可能性。使用可心外膜应用的可收缩贴片可能是改善心室重构和限制继发性细胞迁移的一种方法。

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