Poor functional survival of the engrafted stem cells limits the therapeutic efficacy of stem-cell-based therapy for myocardial infarction (MI). Cardiac patch-based system for cardiac repair has emerged as a potential regenerative strategy for MI. This study aimed to design a cardiac patch to improve the retention of the engrafted stem cells and provide mechanical scaffold for preventing the ventricular remodeling post-MI. The patches were fabricated with electrospinning cellulose nanofibers modified with chitosan/silk fibroin (CS/SF) multilayers via layer-by-layer (LBL) coating technology. The patches engineered with adipose tissue-derived mesenchymal stem cells (AD-MSCs) (cell nano-patch) were adhered to the epicardium of the infarcted region in rat hearts. Bioluminescence imaging (BLI) revealed higher cell viability in the cell nano-patch group compared with the intra-myocardial injection group. Echocardiography demonstrated less ventricular remodeling in cell nano-patch group, with a decrease in the left ventricular end-diastolic volume and left ventricular end-systolic volume compared with the control group. Additionally, left ventricular ejection fraction and fractional shortening were elevated after cell nano-patch treatment compared with the control group. Histopathological staining demonstrated that cardiac fibrosis and apoptosis were attenuated, while local neovascularization was promoted in the cell nano-patch group. Western blot analysis illustrated that the expression of biomarkers for myocardial fibrosis (TGF-β1, P-smad3 and Smad3) and ventricular remodeling (BNP, β-MHC: α-MHC ratio) were decreased in cell nano patch-treated hearts. This study suggests that CS/SF-modified nanofibrous patches promote the functional survival of engrafted AD-MSCs and restrain ventricular remodeling post-MI through attenuating myocardial fibrosis.

Statement of Significance

First, the nanofibrous patches fabricated from the electrospun cellulose nanofibers could mimic the natural extracellular matrix (ECM) of hearts to improve the microenvironment post-MI and provide three dimensional (3D) scaffolds for the engrafted AD-MSCs.

Second, CS and SF which have exhibited excellent properties in previous tissue engineering research, such as nontoxicity, biodegradability, anti-inflammatory, strong hydrophilic nature, high cohesive strength, and intrinsic antibacterial properties further optimized the biocompatibility of the nanofibrous patches via LBL modification.

Finally, the study revealed that beneficial microenvironment and biomimetic ECM improve the retention and viability of the engrafted AD-MSCs and the mechanical action of the cell nano-patches for the expanding ventricular post-MI leads to suppression of HF progression by inhibition of ventricular remodeling.

中文翻译：

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壳聚糖/丝素蛋白修饰的具有间充质干细胞的纳米纤维贴剂可预防大鼠心肌梗死后的心脏重塑

植入的干细胞功能差的生存能力限制了基于干细胞的心肌梗死（MI）治疗的疗效。基于心脏补丁的心脏修复系统已成为MI的潜在再生策略。这项研究旨在设计一种心脏贴片，以改善植入的干细胞的保留，并提供机械支架以防止心梗后心室重构。贴剂是通过静电纺丝的纤维素纳米纤维经壳聚糖/丝素蛋白（CS / SF）多层修饰而制得的。逐层（LBL）涂层技术。用脂肪组织来源的间充质干细胞（AD-MSC）（细胞纳米贴片）改造的贴片粘附在大鼠心脏梗塞区域的心外膜上。生物发光成像（BLI）显示，与心肌内注射组相比，细胞纳米贴片组的细胞活力更高。超声心动图显示，细胞纳米贴片组的心室重构较少，与对照组相比，左心室舒张末期容积和左室收缩末期容积减少。此外，与对照组相比，细胞纳米贴片处理后左心室射血分数和分数缩短缩短。组织病理学染色显示心脏纤维化和细胞凋亡减弱，而在细胞纳米贴片组中促进了局部新血管形成。Western印迹分析表明，在细胞纳米贴片治疗的心脏中，心肌纤维化的生物标志物（TGF-β1，P-smad3和Smad3）的表达和心室重构（BNP，β-MHC：α-MHC比率）降低。这项研究表明，CS / SF修饰的纳米纤维贴剂可促进植入的AD-MSC的功能存活，并通过减轻心肌纤维化来抑制MI后的心室重构。

重要声明

首先，由电纺纤维素纳米纤维制成的纳米纤维贴剂可以模仿心脏的天然细胞外基质（ECM），以改善心肌梗死后的微环境，并为植入的AD-MSC提供三维（3D）支架。

其次，在以前的组织工程研究中表现出优异性能的CS和SF，例如无毒，生物降解性，抗炎性，强亲水性，高内聚强度和固有的抗菌性能，通过LBL修饰进一步优化了纳米纤维贴剂的生物相容性。

最后，该研究表明，有益的微环境和仿生ECM可改善植入的AD-MSC的保留能力和活力，并且细胞纳米片对MI后心室扩大的机械作用可通过抑制心室重构来抑制HF进展。 。