Universite Claude Bernard Lyon 1, UMR 5223, CNRS, INSA Lyon, Universite Jean Monnet, Ingénierie des Matériaux Polymères, F-69622 Villeurbanne, France.
Sorbonne Université, Institut de Biologie Paris-Seine (IBPS), CNRS UMR 8256, Inserm ERL U1164, Biological Adaptation and Ageing, 7 quai St-Bernard (case 256), F-75005 Paris, France.
Int J Biol Macromol. 2024 Nov;281(Pt 4):136400. doi: 10.1016/j.ijbiomac.2024.136400. Epub 2024 Oct 9.
The aim of this work was to assess the potential benefits of the enrichment of a chitosan hydrogel patch with secretome and its epicardial implantation in a murine model of chronic ischemia, focusing on the potential to restore the functional capacity of the heart. Thus, a hydrogel with a final polymer concentration of 3 % was prepared from chitosan with an acetylation degree of 24 % and then bio-functionalized with a secretome produced by mesenchymal stromal cells. The identification of proteins in the secretomes showed the presence of several proteins known to have beneficial effects on cardiac muscle repair. Then chitosan hydrogels were immersed in secretome. The protein incorporation in the hydrogel and their release over time were studied, demonstrating the ability of the gel to retain and then deliver proteins (around 40 % was released in the first 6 h, and then a plateau was reached). Moreover, mechanical analysis exhibited that the patches remained suturable after enrichment. Finally, bio-functionalized hydrogel patches were sutured onto the surface of the infarcted myocardium in rat. Thirty days after, the presence of enriched hydrogels induced a reversion of cardiac function which seems to come mainly from an improvement of left ventricle systolic performance and contractility.
本研究旨在评估富含细胞外囊泡的壳聚糖水凝胶补片的潜在益处，并将其在心梗慢性缺血模型中进行心外膜贴敷，重点关注其恢复心脏功能的潜力。首先，以乙酰化度为 24%的壳聚糖为原料，制备最终聚合物浓度为 3%的水凝胶，然后对其进行生物功能化处理，使其富含间充质基质细胞分泌的细胞外囊泡。对细胞外囊泡中的蛋白质进行鉴定，结果表明其中含有多种已知对心肌修复有益的蛋白质。然后将壳聚糖水凝胶浸入细胞外囊泡中。研究了蛋白质在水凝胶中的掺入及其随时间的释放情况，结果表明该凝胶具有保留和释放蛋白质的能力（在最初的 6 小时内释放了约 40%，随后达到平台期）。此外，力学分析表明，水凝胶补片经富化处理后仍可缝合。最后，将生物功能化的水凝胶补片缝合到大鼠梗死心肌的表面。30 天后，富含细胞外囊泡的水凝胶的存在可逆转心脏功能，这似乎主要来自左心室收缩性能和收缩力的改善。
