Department of Civil, Chemical, Environmental and Materials Engineering, University of Bologna, Via Terracini 28, 40131 Bologna, Italy.
Translational Cardiomyology Laboratory, Stem Cell Biology and Embryology, Department of Development and Regeneration, KU Leuven, Leuven, Belgium.
Biomater Adv. 2023 Nov;154:213583. doi: 10.1016/j.bioadv.2023.213583. Epub 2023 Aug 12.
Cardiac tissue engineering is a cutting-edge technology aiming to replace irreversibly damaged cardiac tissue and restore contractile functionality. However, cardiac tissue engineering porous and perfusable scaffolds to enable oxygen supply in vitro and eventually promote angiogenesis in vivo are still desirable. Two fully-aliphatic random copolymers of poly(butylene succinate) (PBS), poly(butylene succinate/Pripol), P(BSBPripol), and poly(butylene/neopentyl glycol succinate), P(BSNS), containing two different subunits, neopentyl glycol and Pripol 1009, were successfully synthesized and then electrospun in tridimentional fibrous mats. The copolymers show different thermal and mechanical behaviours as result of their chemical structure. In particular, copolymerization led to a reduction in crystallinity and consequently PBS stiffness, reaching values of elastic modulus very close to those of soft tissues. Then, to check the biological suitability, human induced Pluripotent Stem Cells (hiPSCs) were directly seeded on both PBS-based copolymeric scaffolds. The results confirmed the ability of both the scaffolds to sustain cell viability and to maintain their stemness during cell expansion. Furthermore, gene expression and immunofluorescence analysis showed that P(BSBPripol) scaffold promoted an upregulation of the early cardiac progenitor and later-stage markers with a simultaneously upregulation of HYPPO pathway gene expression, crucial for mechanosensing of cardiac progenitor cells. These results suggest that the correct ad-hoc chemical design and, in turn, the mechanical properties of the matrix, such as substrate stiffness, together with surface porosity, play a critical role in regulating the behaviour of cardiac progenitors, which ultimately offers valuable insights into the development of novel bio-inspired scaffolds for cardiac tissue regeneration.
心脏组织工程是一项旨在替代不可逆损伤的心脏组织并恢复收缩功能的尖端技术。然而，仍然需要心脏组织工程的多孔和可灌注支架，以在体外提供氧气供应，并最终促进体内血管生成。两种完全脂肪族聚丁二酸丁二醇酯（PBS）的随机共聚物，聚丁二酸丁二醇酯/普立万（Pripol）共聚物，P(BSBPripol)和聚丁二酸丁二醇酯/新戊二醇/琥珀酸酯，P(BSNS)，含有两个不同的亚单位，新戊二醇和 Pripol 1009，成功地被合成并然后被电纺成三维纤维垫。共聚物由于其化学结构而表现出不同的热和机械性能。特别是共聚作用导致结晶度降低，从而导致 PBS 硬度降低，达到与软组织非常接近的弹性模量值。然后，为了检查生物适宜性，人诱导多能干细胞（hiPSCs）直接接种在两种基于 PBS 的共聚物支架上。结果证实了两种支架都能够维持细胞活力并在细胞扩增过程中保持其干细胞特性。此外，基因表达和免疫荧光分析表明，P(BSBPripol)支架促进了早期心脏祖细胞和后期标志物的上调，同时也上调了 HYPPO 通路基因的表达，这对于心脏祖细胞的机械感应至关重要。这些结果表明，正确的特定化学设计以及基质的机械性能（如基质硬度），与表面孔隙率一起，在调节心脏祖细胞的行为方面起着关键作用，这最终为心脏组织再生的新型仿生支架的开发提供了有价值的见解。
