Experimental Renal and Cardiovascular Research, Department of Nephropathology, Institute of Pathology, University of Erlangen-Nuremberg (FAU), Muscle Research Center Erlangen (MURCE), 91054, Erlangen, Germany.
Department of Physics, University of Erlangen-Nuremberg (FAU), Staudtstr. 7, 91058, Erlangen, Germany.
Adv Healthc Mater. 2023 Aug;12(20):e2202408. doi: 10.1002/adhm.202202408. Epub 2023 Apr 10.
Cardiac tissue engineering is a promising strategy to prevent heart failure. However, several issues remain unsolved, including efficient electrical coupling and incorporating factors to enhance tissue maturation and vascularization. Herein, a biohybrid hydrogel that enhances beating properties of engineered cardiac tissues and allows drug release concurrently is developed. Gold nanoparticles (AuNPs) with different sizes (18-241 nm) and surface charges (33.9-55.4 mV) are synthesized by reducing gold (III) chloride trihydrate using branched polyethyleneimine (bPEI). These nanoparticles increase gel stiffness from ≈91 to ≈146 kPa, enhance electrical conductivity of collagen hydrogels from ≈40 to 49-68 mS cm , and allow slow and steady release of loaded drugs. Engineered cardiac tissues based on bPEI-AuNP-collagen hydrogels and either primary or human induced pluripotent stem cell (hiPSC)-derived cardiomyocytes show enhanced beating properties. hiPSC-derived cardiomyocytes exhibit more aligned and wider sarcomeres in bPEI-AuNP-collagen hydrogels compared to collagen hydrogels. Furthermore, the presence of bPEI-AuNPs result in advanced electrical coupling evidenced by synchronous and homogenous calcium flux throughout the tissue. RNA-seq analyses are in agreement with these observations. Collectively, this data demonstrate the potential of bPEI-AuNP-collagen hydrogels to improve tissue engineering approaches to prevent heart failure and possibly treat diseases of other electrically sensitive tissues.
心脏组织工程学是预防心力衰竭的一种很有前途的策略。然而，仍有几个问题尚未解决，包括有效的电偶联以及加入促进组织成熟和血管化的因素。在此，开发了一种生物杂化水凝胶，该水凝胶可增强工程化心脏组织的搏动特性，并可同时进行药物释放。通过使用支化聚乙烯亚胺（bPEI）还原三氯化金三水合物合成了具有不同尺寸（18-241nm）和表面电荷（33.9-55.4mV）的金纳米粒子（AuNPs）。这些纳米粒子将凝胶的刚度从约 91kPa 增加到约 146kPa，将胶原蛋白水凝胶的电导率从约 40mS/cm 增加到 49-68mS/cm，并允许负载药物的缓慢而稳定的释放。基于 bPEI-AuNP-胶原蛋白水凝胶的工程化心脏组织以及原代或人诱导多能干细胞（hiPSC）衍生的心肌细胞表现出增强的搏动特性。与胶原蛋白水凝胶相比，bPEI-AuNP-胶原蛋白水凝胶中的 hiPSC 衍生的心肌细胞显示出更对齐和更宽的肌节。此外，bPEI-AuNPs 的存在导致电偶联得到改善，表现为整个组织中钙通量同步且均匀。RNA-seq 分析与这些观察结果一致。总的来说，这些数据表明 bPEI-AuNP-胶原蛋白水凝胶有潜力改善组织工程方法，以预防心力衰竭，并可能治疗其他对电敏感的组织的疾病。
