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一种用于递送基质细胞衍生因子1的多模态支架可改善大鼠亚急性心肌梗死模型的心脏功能。

A Multimodal Scaffold for SDF1 Delivery Improves Cardiac Function in a Rat Subacute Myocardial Infarct Model.

作者信息

Perez-Estenaga Iñigo, Chevalier Merari Tumin, Peña Estefania, Abizanda Gloria, Alsharabasy Amir M, Larequi Eduardo, Cilla Myriam, Perez Marta M, Gurtubay Jon, Garcia-Yebenes Castro Manuel, Prosper Felipe, Pandit Abhay, Pelacho Beatriz

机构信息

Regenerative Medicine Department, Center for Applied Medical Research (CIMA), University of Navarra, Pamplona 31008, Spain.

CÚRAM, SFI Research Center for Medical Devices, University of Galway, Galway H91 TK33, Ireland.

出版信息

ACS Appl Mater Interfaces. 2023 Aug 11;15(44):50638-51. doi: 10.1021/acsami.3c04245.

Abstract

Ischemic heart disease is one of the leading causes of death worldwide. The efficient delivery of therapeutic growth factors could counteract the adverse prognosis of post-myocardial infarction (post-MI). In this study, a collagen hydrogel that is able to load and appropriately deliver pro-angiogenic stromal cell-derived factor 1 (SDF1) was physically coupled with a compact collagen membrane in order to provide the suture strength required for surgical implantation. This bilayer collagen-on-collagen scaffold (bCS) showed the suitable physicochemical properties that are needed for efficient implantation, and the scaffold was able to deliver therapeutic growth factors after MI. collagen matrix biodegradation led to a sustained SDF1 release and a lack of cytotoxicity in the relevant cell cultures. intervention in a rat subacute MI model resulted in the full integration of the scaffold into the heart after implantation and biocompatibility with the tissue, with a prevalence of anti-inflammatory and pro-angiogenic macrophages, as well as evidence of revascularization and improved cardiac function after 60 days. Moreover, the beneficial effect of the released SDF1 on heart remodeling was confirmed by a significant reduction in cardiac tissue stiffness. Our findings demonstrate that this multimodal scaffold is a desirable matrix that can be used as a drug delivery system and a scaffolding material to promote functional recovery after MI.

摘要

缺血性心脏病是全球主要死因之一。有效递送治疗性生长因子可对抗心肌梗死后的不良预后。在本研究中,一种能够负载并适当递送促血管生成的基质细胞衍生因子1(SDF1)的胶原水凝胶与致密胶原膜物理结合,以提供手术植入所需的缝合强度。这种双层胶原-胶原支架(bCS)表现出有效植入所需的合适物理化学性质,并且该支架能够在心肌梗死后递送治疗性生长因子。胶原基质的生物降解导致SDF1的持续释放以及相关细胞培养物中无细胞毒性。在大鼠亚急性心肌梗死模型中的干预导致植入后支架完全整合到心脏中并与组织具有生物相容性,存在抗炎和促血管生成的巨噬细胞,并且在60天后有血管再生和心脏功能改善的证据。此外,释放的SDF1对心脏重塑的有益作用通过心脏组织硬度的显著降低得到证实。我们的研究结果表明,这种多模式支架是一种理想的基质,可作为药物递送系统和支架材料来促进心肌梗死后的功能恢复。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/80fd/10636708/92db1f5320e3/am3c04245_0001.jpg

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