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Efficacy of epicardial implantation of acellular chitosan hydrogels in ischemic and nonischemic heart failure: impact of the acetylation degree of chitosan
Acta Biomaterialia ( IF 9.4 ) Pub Date : 2020-11-06 , DOI: 10.1016/j.actbio.2020.10.045
Orianne Domengé , Hélène Ragot , Robin Deloux , Agnès Crépet , Gaëlle Revet , Solène Emmanuelle Boitard , Alexandre Simon , Nathalie Mougenot , Laurent David , Thierry Delair , Alexandra Montembault , Onnik Agbulut

This work explores the epicardial implantation of acellular chitosan hydrogels in two murine models of cardiomyopathy, focusing on their potential to restore the functional capacity of the heart. Different chitosan hydrogels were generated using polymers of four degrees of acetylation, ranging from 2.5% to 38%, because the degree of acetylation affects their degradation and biological activity. The hydrogels were adjusted to a 3% final polymer concentration. After complete macromolecular characterization of the chitosans and study of the mechanical properties of the resulting hydrogels, they were sutured onto the surface of the myocardium, first in rat after four-weeks of coronary ligation (n=58) then in mice with cardiomyopathy induced by a cardiac-specific invalidation of serum response factor (n=20). The implantation of the hydrogels was associated with a reversion of cardiac function loss with maximal effects for the acetylation degree of 24%. The extent of fibrosis, the cardiomyocyte length-to-width ratio, as well as the genes involved in fibrosis and stress were repressed after implantation. Our study demonstrated the beneficial effects of chitosan hydrogels, particularly with polymers of high degrees of acetylation, on cardiac remodeling in two cardiomyopathy models. Our findings indicate they have great potential as a reliable therapeutic approach to heart failure.



中文翻译:

脱细胞壳聚糖水凝胶心外膜植入在缺血性和非缺血性心力衰竭中的疗效:壳聚糖乙酰化程度的影响

这项工作探讨了脱细胞壳聚糖水凝胶在两种心肌病小鼠模型的心外膜植入,重点在于它们恢复心脏功能能力的潜力。使用乙酰化度为2.5%至38%的四个乙酰化度的聚合物可生成不同的壳聚糖水凝胶,因为乙酰化度会影响其降解和生物活性。将水凝胶调节至3%的最终聚合物浓度。在对壳聚糖进行完整的大分子表征并研究所得水凝胶的机械性能后,将它们缝合到心肌表面,首先在大鼠进行冠状动脉结扎四周后(n = 58),然后在大鼠中由环丙沙星诱导心脏特异性血清反应因子无效(n = 20)。水凝胶的植入与心脏功能丧失的恢复相关,乙酰化程度为24%时效果最大。植入后,纤维化程度,心肌细胞长宽比以及参与纤维化和应激的基因被抑制。我们的研究表明,壳聚糖水凝胶,特别是高度乙酰化的聚合物,对两种心肌病模型的心脏重构具有有益作用。我们的发现表明它们作为治疗心力衰竭的可靠方法具有巨大潜力。我们的研究表明,壳聚糖水凝胶,特别是高度乙酰化的聚合物,对两种心肌病模型的心脏重构具有有益作用。我们的发现表明它们作为治疗心力衰竭的可靠方法具有巨大潜力。我们的研究表明,壳聚糖水凝胶,特别是高度乙酰化的聚合物,对两种心肌病模型的心脏重构具有有益作用。我们的发现表明它们作为治疗心力衰竭的可靠方法具有巨大潜力。

更新日期:2020-12-11
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