One of the major challenges in cardiac cell therapy is cell death and low rate of cardiac differentiation. In this regard, a series of thermosensitive and injectable hydrogels with similar physicomechanical properties of cardiac tissue can be an ideal candidate for delivering human unrestricted somatic stem cells (hUSSCs) and improve the quality of cell therapy. Here, we designed N-isopropylacrylamide/acrylic acid/N-acryloxysuccinimide/2-hydroxyethyl methacrylate-poly lactide (NIPAAm/AAc/NAS/HEMAPLA) hydrogel via ring-opening polymerization for encapsulation of the cells. To improve biological activities, biomaterials like hyaluronic acid (HA), Aloe vera (AV), and silk fibroin (SF) were added with pure hydrogel (Pgel). The modulus of hydrogels was estimated between 68.1 and 74.63 kPa that was similar to the normal cardiac modulus. Moreover, the elastic region increased by adding biomaterials to Pgel. The results of RT-PCR and ICC demonstrated that the most expression of early genes (GATA4, NKX2.5) was related to Pgel/AV/SF group. In contrast, the highest expression of other genes (GJA1, TNNI3, MYH6) was observed in Pgel/HA/SF. The presence of biomaterials in the structure of hydrogel can play a key role in cell fate and the induction of cell differentiation as a factor influencing mechanotransduction. These hydrogels hold an excellent promise to deliver hUSSCs into damaged tissue for cardiac regeneration.

心脏细胞治疗的主要挑战之一是细胞死亡和心脏分化率低。在这方面，一系列具有类似心脏组织物理机械特性的热敏性和可注射水凝胶可以成为递送人类无限制体干细胞（hUSSCs）并改善细胞治疗质量的理想候选者。在这里，我们通过开环聚合设计了N-异丙基丙烯酰胺/丙烯酸/ N-丙烯酰氧基琥珀酰亚胺/ 2-甲基丙烯酸羟乙酯-聚丙交酯（NIPAAm / AAc / NAS / HEMAPLA）水凝胶，用于细胞封装。为了提高生物活性，透明质酸（HA），芦荟等生物材料（AV）和丝素蛋白（SF）加入纯水凝胶（Pgel）。水凝胶的模量估计在68.1至74.63 kPa之间，与正常的心脏模量相似。此外，通过向Pgel添加生物材料来增加弹性区域。RT-PCR和ICC的结果表明，早期基因（GATA4，NKX2.5）的表达最多与Pgel / AV / SF组有关。相反，在Pgel / HA / SF中观察到其他基因（GJA1，TNNI3，MYH6）的最高表达。水凝胶结构中生物材料的存在可在细胞命运和诱导细胞分化中发挥重要作用，而细胞分化是影响机械转导的因素。这些水凝胶极有希望将hUSSCs输送到受损的组织中以进行心脏再生。