Institute of Material Science of Barcelona (ICMAB), CSIC, Campus UAB, 08193 Bellaterra, Spain.
IMEM-BRT Group, Departament de Ciència i Enginyeria de Materials, Universitat Politecnica de Catalunya, 08028 Barcelona, Spain.
ACS Appl Bio Mater. 2023 Jul 17;6(7):2860-2874. doi: 10.1021/acsabm.3c00303. Epub 2023 Jun 21.
The low endogenous regenerative capacity of the heart, added to the prevalence of cardiovascular diseases, triggered the advent of cardiac tissue engineering in the last decades. The myocardial niche plays a critical role in directing the function and fate of cardiomyocytes; therefore, engineering a biomimetic scaffold holds excellent promise. We produced an electroconductive cardiac patch of bacterial nanocellulose (BC) with polypyrrole nanoparticles (Ppy NPs) to mimic the natural myocardial microenvironment. BC offers a 3D interconnected fiber structure with high flexibility, which is ideal for hosting Ppy nanoparticles. BC-Ppy composites were produced by decorating the network of BC fibers (65 ± 12 nm) with conductive Ppy nanoparticles (83 ± 8 nm). Ppy NPs effectively augment the conductivity, surface roughness, and thickness of BC composites despite reducing scaffolds' transparency. BC-Ppy composites were flexible (up to 10 mM Ppy), maintained their intricate 3D extracellular matrix-like mesh structure in all Ppy concentrations tested, and displayed electrical conductivities in the range of native cardiac tissue. Furthermore, these materials exhibit tensile strength, surface roughness, and wettability values appropriate for their final use as cardiac patches. experiments with cardiac fibroblasts and H9c2 cells confirmed the exceptional biocompatibility of BC-Ppy composites. BC-Ppy scaffolds improved cell viability and attachment, promoting a desirable cardiomyoblast morphology. Biochemical analyses revealed that H9c2 cells showed different cardiomyocyte phenotypes and distinct levels of maturity depending on the amount of Ppy in the substrate used. Specifically, the employment of BC-Ppy composites drives partial H9c2 differentiation toward a cardiomyocyte-like phenotype. The scaffolds increase the expression of functional cardiac markers in H9c2 cells, indicative of a higher differentiation efficiency, which is not observed with plain BC. Our results highlight the remarkable potential use of BC-Ppy scaffolds as a cardiac patch in tissue regenerative therapies.
心脏的内源性再生能力较低，加上心血管疾病的高发，促使心脏组织工程在过去几十年中问世。心肌龛在指导心肌细胞的功能和命运方面起着至关重要的作用；因此，工程仿生支架具有巨大的潜力。我们制作了一种带有聚吡咯纳米粒子（Ppy NPs）的细菌纳米纤维素（BC）导电心脏贴片，以模拟天然心肌微环境。BC 提供了具有高柔韧性的 3D 相互连接的纤维结构，非常适合容纳 Ppy 纳米粒子。通过在 BC 纤维网络（65 ± 12 nm）上装饰导电 Ppy 纳米粒子（83 ± 8 nm）来制备 BC-Ppy 复合材料。尽管降低了支架的透明度，但 Ppy NPs 可有效提高 BC 复合材料的导电性、表面粗糙度和厚度。BC-Ppy 复合材料具有柔韧性（高达 10 mM Ppy），在所有测试的 Ppy 浓度下都保持其错综复杂的 3D 细胞外基质样网状结构，并显示出与天然心肌组织相当的电导率。此外，这些材料具有适当的拉伸强度、表面粗糙度和润湿性，适合最终用作心脏贴片。对心脏成纤维细胞和 H9c2 细胞的实验证实了 BC-Ppy 复合材料的出色生物相容性。BC-Ppy 支架提高了细胞活力和附着性，促进了理想的心肌细胞形态。生化分析表明，H9c2 细胞根据所用基底中 Ppy 的量表现出不同的心肌细胞表型和不同的成熟程度。具体而言，BC-Ppy 复合材料的使用促使 H9c2 细胞部分分化为心肌细胞样表型。支架增加了 H9c2 细胞中功能性心脏标志物的表达，表明分化效率更高，而这在纯 BC 中是观察不到的。我们的结果突出了 BC-Ppy 支架作为组织再生治疗中心脏贴片的显著潜在用途。
