Histologic Evaluation of Therapeutic Responses in Ischemic Myocardium Elicited by Dual Growth Factor Delivery from Composite Glycosaminoglycan Hydrogels

Alexander A Xu, Kayle S. Shapero, Jared A. Geibig, Hsiang-Wei K. Ma, Alex R. Jones, Marina Hanna, Daniel R. Pitts, E. Hillas, M. Firpo, R. Peattie
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Abstract

In this project, the ability of dual growth factor-preloaded, silk-reinforced, composite hyaluronic acid-based hydrogels to elicit advantageous histologic responses when secured to ischemic myocardium was evaluated in vivo. Reinforced hydrogels containing both Vascular Endothelial Growth Factor (VEGF) and Platelet-derived Growth Factor (PDGF) were prepared by crosslinking chemically modified hyaluronic acid and heparin with poly(ethylene glycol)-diacrylate around a reinforcing silk mesh. Composite patches were sutured to the ventricular surface of ischemic myocardium in Sprague-Dawley rats, and the resulting angiogenic response was followed for 28 days. The gross appearance of treated hearts showed significantly reduced ischemic area and fibrous deposition compared to untreated control hearts. Histologic evaluation showed growth factor delivery to restore myofiber orientation to pre-surgical levels and to significantly increase elicited microvessel density and maturity by day 28 in infarcted myocardial tissue (p < 0.05). In addition, growth factor delivery reduced cell apoptosis and decreased the density of elicited mast cells and both CD68+ and anti-inflammatory CD163+ macrophages. These findings suggest that HA-based, dual growth factor-loaded hydrogels can successfully induce a series of beneficial responses in ischemic myocardium, and offer the potential for therapeutic improvement of ischemic myocardial remodeling.
复合糖胺聚糖水凝胶双生长因子递送诱导缺血心肌治疗反应的组织学评价
在这个项目中,我们在体内评估了双生长因子预负载、丝增强、复合透明质酸基水凝胶在保护缺血心肌时引发有利组织学反应的能力。将化学修饰的透明质酸和肝素与聚乙二醇-二丙烯酸酯在增强丝网周围交联,制备了含有血管内皮生长因子(VEGF)和血小板衍生生长因子(PDGF)的增强水凝胶。将复合贴片缝合于Sprague-Dawley大鼠缺血心肌的心室表面,观察28天的血管生成反应。与未治疗的对照组心脏相比,治疗后心脏的大体外观显示缺血面积和纤维沉积明显减少。组织学评价显示,在梗死心肌组织中,生长因子递送可使肌纤维取向恢复到术前水平,并在第28天显著增加诱导的微血管密度和成熟度(p < 0.05)。此外,生长因子递送可减少细胞凋亡,降低诱导肥大细胞和CD68+和抗炎CD163+巨噬细胞的密度。这些研究结果表明,基于ha的双生长因子负载水凝胶可以成功诱导缺血性心肌的一系列有益反应,并为缺血性心肌重构的治疗改善提供了潜力。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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