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聚左旋乳酸粒细胞集落刺激因子功能化支架在慢性心肌梗死模型中的植入

Implantation of a Poly-L-Lactide GCSF-Functionalized Scaffold in a Model of Chronic Myocardial Infarction.

作者信息

Spadaccio Cristiano, Nappi Francesco, De Marco Federico, Sedati Pietro, Taffon Chiara, Nenna Antonio, Crescenzi Anna, Chello Massimo, Trombetta Marcella, Gambardella Ivancarmine, Rainer Alberto

机构信息

Department of Cardiothoracic Surgery, Golden Jubilee National Hospital, Agamemnon Street Clydebank, Glasgow, G81 4DY, UK.

Institute of Cardiovascular and Medical Sciences, College of Medical, Veterinary and Life Sciences, University of Glasgow, Glasgow, UK.

出版信息

J Cardiovasc Transl Res. 2017 Feb;10(1):47-65. doi: 10.1007/s12265-016-9718-9. Epub 2017 Jan 23.

Abstract

A previously developed poly-L-lactide scaffold releasing granulocyte colony-stimulating factor (PLLA/GCSF) was tested in a rabbit chronic model of myocardial infarction (MI) as a ventricular patch. Control groups were constituted by healthy, chronic MI and nonfunctionalized PLLA scaffold. PLLA-based electrospun scaffold efficiently integrated into a chronic infarcted myocardium. Functionalization of the biopolymer with GCSF led to increased fibroblast-like vimentin-positive cellular colonization and reduced inflammatory cell infiltration within the micrometric fiber mesh in comparison to nonfunctionalized scaffold; PLLA/GCSF polymer induced an angiogenetic process with a statistically significant increase in the number of neovessels compared to the nonfunctionalized scaffold; PLLA/GCSF implanted at the infarcted zone induced a reorganization of the ECM architecture leading to connective tissue deposition and scar remodeling. These findings were coupled with a reduction in end-systolic and end-diastolic volumes, indicating a preventive effect of the scaffold on ventricular dilation, and an improvement in cardiac performance.

摘要

一种先前开发的可释放粒细胞集落刺激因子的聚-L-丙交酯支架(PLLA/GCSF)作为心室补片在兔慢性心肌梗死(MI)模型中进行了测试。对照组由健康、慢性MI和未功能化的PLLA支架组成。基于PLLA的电纺支架有效地整合到慢性梗死心肌中。与未功能化支架相比,用GCSF对生物聚合物进行功能化导致成纤维细胞样波形蛋白阳性细胞定植增加,微米级纤维网内的炎性细胞浸润减少;PLLA/GCSF聚合物诱导血管生成过程,与未功能化支架相比,新生血管数量有统计学意义的增加;植入梗死区的PLLA/GCSF诱导细胞外基质结构重组,导致结缔组织沉积和瘢痕重塑。这些发现伴随着收缩末期和舒张末期容积的减少,表明支架对心室扩张有预防作用,并改善了心脏功能。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6b29/5323505/74530f2cde39/12265_2016_9718_Fig1_HTML.jpg

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