海藻酸钠-不溶性细胞外基质复合水凝胶的心包递送促进心肌梗塞后的血管生成和细胞间导电。
Pericardial Delivery of Sodium Alginate-Infusible Extracellular Matrix Composite Hydrogel Promotes Angiogenesis and Intercellular Electrical Conduction after Myocardial Infarction.
发表日期:2024 Aug 15
作者:
Dahe Liu, Yajing Li, Ziwei Bao, Jiaqi He, Yanxing Lan, Zijun Xu, Guoqin Chen
来源:
HEART & LUNG
摘要:
可注射细胞外基质(iECM)是一种多功能生物材料,具有良好的降解性、促进细胞存活、免疫调节和促进血管形成等有益特性。然而,静脉注射iECM面临着体内保留时间短、病灶部位浓度低等挑战。为了解决这些问题,我们制备了一种由海藻酸钠和 iECM 组成的复合水凝胶,并通过心包内注射进行给药,在心包内形成类似于心脏贴片的结构。与心肌内注射相比,心包内注射避免了直接的心肌损伤和异位肿瘤的形成,具有较小的侵入性和更好的生物相容性。本研究表明,海藻酸钠/不熔细胞外基质(SA/iECM)复合水凝胶可以有效延长iECM在心脏的局部保留时间,增强心肌细胞间的导电,促进缺血心肌部位的血管生成,抑制梗死区域的细胞凋亡,减轻心肌梗塞(MI)后左心室重构,改善梗塞后心功能。心肌细胞收缩和舒张的精确协调取决于钙依赖性动作电位的节律发生。心脏功能障碍部分归因于兴奋-收缩耦合 (ECC) 机制的破坏,该机制与细胞内 Ca2 瞬变延长以及收缩和舒张 Ca2 水平的改变有关。我们的结果表明,SA/iECM 复合水凝胶可改善电传导,Cx43 表达增加和细胞间电连接增强就证明了这一点。该研究证实心包内注射SA/iECM复合水凝胶是一种安全有效的治疗方式,为生物材料在心肌梗死治疗中的应用提供了理论基础。
Injectable extracellular matrix (iECM) is a versatile biological material with beneficial properties such as good degradability, promotion of cell survival, immunomodulation, and facilitation of vascular formation. However, intravenous injection of iECM faces challenges like a short retention time in vivo and low concentration at the lesion site. To address these issues, we prepared a composite hydrogel composed of sodium alginate and iECM and administered it via intrapericardial injection, forming a structure akin to cardiac patches within the pericardium. Compared with intramyocardial injection, intrapericardial injection avoids direct myocardial injury and ectopic tumor formation, offering less invasiveness and better biocompatibility. This study demonstrates that the sodium alginate/infusible extracellular matrix (SA/iECM) composite hydrogel can effectively prolong the local retention time of iECM in the heart, enhance electrical conduction between cardiomyocytes, promote angiogenesis at ischemic myocardial sites, inhibit apoptosis in the infarcted region, mitigate left ventricular remodeling postmyocardial infarction (MI), and improve cardiac function after infarction. Precise coordination of cardiomyocyte contraction and relaxation depends on the rhythmic occurrence of calcium-dependent action potentials. Cardiac dysfunction is partially attributed to the disruption of the excitation-contraction coupling (ECC) mechanism, which is associated with prolonged intracellular Ca2+ transients and alterations in contraction and relaxation Ca2+ levels. Our results show that the SA/iECM composite hydrogel improves electrical conduction, as evidenced by increased Cx43 expression and enhanced intercellular electrical connectivity. This research establishes that intrapericardial injection of a SA/iECM composite hydrogel is a safe and effective treatment modality, providing a theoretical basis for the use of biomaterials in MI therapy.