School of Medicine, Xiamen University, Xiamen, Fujian Province, People's Republic of China.
Emergency, Zhongshan Hospital, Xiamen University, Xiamen, Fujian Province, People's Republic of China.
J Biomed Mater Res A. 2020 Jun;108(6):1351-1368. doi: 10.1002/jbm.a.36907. Epub 2020 Mar 2.
The prosthetic mesh, which is widely used in tension-free hernioplasty, often result in avascular stiff fibrotic scar or mesh shrinkage, causing chronic pain and infection. Here, we developed an autologous bionic tissue (ABT), which was composed of autologous bone marrow-derived mesenchymal stem cells (MSCs), poly (lactic-co-glycolic acid) (PLGA) porous scaffolds, and extracellular matrix (ECM) produced by MSCs for inguinal hernioplasty. In ABT, MSCs produced a variety of ECM composites, such as structural proteins (insoluble collagen, elastin) that provided mechanical properties, macromolecules (hyaluronic acid, glycosaminoglycan) as water and cytokines reservoir, and cell-engaging proteins (fibronectin, laminin). The above ECM composites reached the highest level in 21 days. ECM degradation related cytokines (MMP-9 and its inhibitor TIMP-1) reached the highest level on the 14th day. ECM increased the mechanical properties, elasticity, and flexibility of PLGA. Compared with the PLGA, ABT greatly inhibited inflammatory factors and promoted anti-inflammatory factors (p < 0.05), and gradually reduced the M1/M2 ratio in vivo (p < 0.05). After implantation, the thickness of tissue regeneration (p < 0.05), the number of capillaries or mature vessels (p < 0.05), the mechanical properties of ABT (p < 0.05) were greater than PLGA. MSCs and ECM could reduce the inflammation caused by PLGA, and prevent PLGA from earlier degradation and facilitate host cellular infiltration, thus ABT could greatly promote tissue regeneration in hernia repairs.
用于无张力疝修补术的补片通常会导致无血管的僵硬纤维疤痕或补片收缩,从而引起慢性疼痛和感染。在这里,我们开发了一种自体仿生组织(ABT),它由自体骨髓间充质干细胞(MSCs)、聚(乳酸-共-乙醇酸)(PLGA)多孔支架和 MSCs 产生的细胞外基质(ECM)组成,用于腹股沟疝修补术。在 ABT 中,MSCs 产生了多种 ECM 复合材料,如结构蛋白(不溶性胶原蛋白、弹性蛋白),提供机械性能,大分子(透明质酸、糖胺聚糖)作为水和细胞因子的储库,以及细胞结合蛋白(纤维连接蛋白、层粘连蛋白)。上述 ECM 复合材料在第 21 天达到最高水平。ECM 降解相关细胞因子(MMP-9 及其抑制剂 TIMP-1)在第 14 天达到最高水平。ECM 增加了 PLGA 的机械性能、弹性和柔韧性。与 PLGA 相比,ABT 极大地抑制了炎症因子,促进了抗炎因子(p < 0.05),并逐渐降低了体内 M1/M2 比值(p < 0.05)。植入后,组织再生的厚度(p < 0.05)、毛细血管或成熟血管的数量(p < 0.05)、ABT 的机械性能(p < 0.05)均大于 PLGA。MSCs 和 ECM 可以减少 PLGA 引起的炎症,防止 PLGA 过早降解,并促进宿主细胞浸润,从而大大促进疝修补中的组织再生。