Department of Bioengineering, University of Colorado Anschutz Medical Campus, 12705 E Montview Blvd, Suite 100, Aurora 80045, CO, USA.
Department of Biomedical Engineering, University of Texas at Austin, Austin, TX, USA.
Acta Biomater. 2020 Jan 1;101:206-218. doi: 10.1016/j.actbio.2019.10.026. Epub 2019 Oct 22.
Congenital heart defects affect about 1% births in the United States. Many of the defects are treated with surgically implanted patches made from inactive materials or fixed pericardium that do not grow with the patients, leading to an increased risk of arrhythmia, sudden cardiac death, and heart failure. This study investigated an angiogenic poly(ethylene glycol) fibrin-based hydrogel reinforced with an electrospun biodegradable poly(ether ester urethane) urea (BPUR) mesh layer that was designed to encourage cell invasion, angiogenesis, and regenerative remodeling in the repair of an artificial defect created onto the rat right ventricle wall. Electrocardiogram signals were analyzed, heart function was measured, and fibrosis, macrophage infiltration, muscularization, vascularization, and defect size were evaluated at 4- and 8-weeks post-surgery. Compared with rats with fixed pericardium patches, rats with BPUR-reinforced hydrogel patches had fewer arrhythmias and greater right ventricular ejection fraction and cardiac output, as well as greater left ventricular ejection fraction, fractional shorting, stroke work and cardiac output. Histology and immunofluorescence staining showed less fibrosis and less patch material remaining in rats with BPUR-reinforced hydrogel patches at 4- and 8-weeks. Rats with BPUR-reinforced hydrogel patches also had a greater volume of granular tissue, a greater volume of muscularized tissue, more blood vessels, and a greater number of leukocytes, pan-macrophages, and M2 macrophages at 8 weeks. Overall, this study demonstrated that the engineered BPUR-reinforced hydrogel patch initiated greater regenerative vascular and muscular remodeling with a limited fibrotic response, resulting in fewer incidences of arrhythmia and improved heart function compared with fixed pericardium patches when applied to heal the defects created on the rat right ventricle wall. STATEMENT OF SIGNIFICANCE: The study tested a polyurethane-reinforced hydrogel patch in a rat right ventricle wall replacement model. Compared with fixed pericardium patches, these reinforced hydrogel patches initiated greater regenerative vascular and muscular remodeling with a reduced fibrotic response, resulting in fewer incidences of arrhythmia and improved heart function at 4- and 8-weeks post surgery. Overall, the new BPUR-reinforced hydrogel patches resulted in better heart function when replacing contractile myocardium than fixed pericardium patches.
先天性心脏缺陷影响美国约 1%的新生儿。许多缺陷采用外科植入的补丁进行治疗，这些补丁由非活性材料或固定的心包膜制成，不能随患者生长，导致心律失常、心脏性猝死和心力衰竭的风险增加。本研究调查了一种血管生成的聚（乙二醇）纤维蛋白基水凝胶，该水凝胶用静电纺丝可生物降解的聚（醚酯尿烷）尿素（BPUR）网层增强，旨在促进细胞浸润、血管生成和再生重塑，以修复大鼠右心室壁上创建的人工缺陷。分析了心电图信号，测量了心功能，并在手术后 4 周和 8 周评估了纤维化、巨噬细胞浸润、肌化、血管化和缺陷大小。与固定的心包膜补丁的大鼠相比，用 BPUR 增强水凝胶补丁的大鼠心律失常更少，右心室射血分数和心输出量更大，左心室射血分数、分数缩短、冲程工作和心输出量也更大。组织学和免疫荧光染色显示，在 4 周和 8 周时，用 BPUR 增强水凝胶补丁的大鼠中纤维化和剩余补丁材料更少。用 BPUR 增强水凝胶补丁的大鼠在 8 周时也有更大的颗粒组织体积、更大的肌化组织体积、更多的血管和更多的白细胞、全巨噬细胞和 M2 巨噬细胞。总的来说，这项研究表明，与固定的心包膜补丁相比，该工程 BPUR 增强水凝胶补丁引发了更大的再生血管和肌肉重塑，纤维化反应有限，导致心律失常的发生率更低，心脏功能得到改善，当应用于修复大鼠右心室壁上创建的缺陷时。意义声明：该研究在大鼠右心室壁置换模型中测试了一种聚氨酯增强水凝胶补丁。与固定的心包膜补丁相比，这些增强水凝胶补丁引发了更大的再生血管和肌肉重塑，纤维化反应减少，术后 4 周和 8 周心律失常的发生率降低，心脏功能改善。总的来说，与固定的心包膜补丁相比，新型 BPUR 增强水凝胶补丁在替换收缩性心肌时能更好地改善心脏功能。
