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一种用于心肌组织工程的可生物降解、微结构化、导电且纳米集成的药物洗脱贴片(MENDEP)。

A biodegradable, microstructured, electroconductive and nano-integrated drug eluting patch (MENDEP) for myocardial tissue engineering.

作者信息

Cristallini Caterina, Rossin Daniela, Vanni Roberto, Barbani Niccoletta, Bulgheresi Chiara, Labardi Massimiliano, Perveen Sadia, Burchielli Silvia, Terlizzi Domiziana, Kusmic Claudia, Del Ry Silvia, Cabiati Manuela, Trouki Cheherazade, Rossino Dawid, Sergi Francesca, Villano Anthea, Aquaro Giovanni D, Scarpellino Giorgia, Ruffinatti Federico A, Amorim Sara, Pires Ricardo A, Reis Rui L, Rastaldo Raffaella, Giachino Claudia

机构信息

Institute for Chemical and Physical Processes, CNR-IPCF, Via Giuseppe Moruzzi 1, 56124, Pisa, Italy.

Department of Civil and Industrial Engineering, DICI, University of Pisa, Largo Lucio Lazzarino, 56126, Pisa, Italy.

出版信息

Bioact Mater. 2025 Apr 14;50:246-272. doi: 10.1016/j.bioactmat.2025.04.008. eCollection 2025 Aug.

Abstract

We produced a microstructured, electroconductive and nano-functionalized drug eluting cardiac patch (MENDEP) designed to attract endogenous precursor cells, favor their differentiation and counteract adverse ventricular remodeling . MENDEP showed mechanical anisotropy and biaxial strength comparable to porcine myocardium, reduced impedance, controlled biodegradability, molecular recognition ability and controlled drug release activity. , cytocompatibility and cardioinductivity were demonstrated. Migration tests showed the chemoattractive capacity of the patches and conductivity assays showed unaltered cell-cell interactions and cell beating synchronicity. MENDEP was then epicardially implanted in a rat model of ischemia/reperfusion (I/R). Histological, immunofluorescence and biomarker analysis indicated that implantation did not cause damage to the healthy myocardium. After I/R, MENDEP recruited precursor cells into the damaged myocardium and triggered their differentiation towards the vascular lineage. Under the patch, the myocardial tissue appeared well preserved and cardiac gap junctions were correctly distributed at the level of the intercalated discs. The fibrotic area measured in the I/R group was partially reduced in the patch group. Overall, these results demonstrate that MENDEP was fully retained on the epicardial surface of the left ventricle over 4-week implantation period, underwent progressive vascularization, did not perturb the healthy myocardium and showed great potential in repairing the infarcted area.

摘要

我们制备了一种微结构化、导电且具有纳米功能化的药物洗脱心脏贴片(MENDEP),其设计目的是吸引内源性前体细胞,促进它们的分化并对抗心室不良重塑。MENDEP表现出与猪心肌相当的机械各向异性和双轴强度,阻抗降低,具有可控的生物降解性、分子识别能力和可控的药物释放活性。已证实其具有细胞相容性和心脏诱导性。迁移试验显示了贴片的化学吸引能力,电导率测定显示细胞间相互作用和细胞跳动同步性未改变。然后将MENDEP心外膜植入缺血/再灌注(I/R)大鼠模型中。组织学、免疫荧光和生物标志物分析表明,植入并未对健康心肌造成损伤。I/R后,MENDEP将前体细胞募集到受损心肌中,并触发它们向血管谱系分化。在贴片下方,心肌组织保存良好,心脏间隙连接在闰盘水平正确分布。贴片组中I/R组测得的纤维化面积部分减少。总体而言,这些结果表明,MENDEP在4周的植入期内完全保留在左心室的心外膜表面,经历了渐进性血管化,未干扰健康心肌,并且在修复梗死区域方面显示出巨大潜力。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/88b9/12017858/de5a518da1ce/ga1.jpg

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