止血材料通常应用于癌症的外科手术中,但它们对肿瘤生长和复发的影响尚不清楚。在这里,三种常用的天然止血材料,明胶海绵,Surgicel(氧化再生纤维素),和生物膜(透明质酸钠和羧甲基壳聚糖的混合物),与A549人肺腺癌细胞体外共培养。此外,皮下植入BALB/c小鼠后,观察止血材料的性能和材料与A549细胞的致瘤性。体外实验结果表明,生物纸迅速溶解,在培养2天和4天时具有最高的细胞数。明胶海绵保留了其结构,并在2至10天的培养过程中引起最少的细胞浸润。Surgicel部分溶解并随时间支持细胞生长。体内实验结果表明,生物纸在植入后3天迅速降解并引起急性Th1淋巴细胞反应,植入后7天下降。明胶海绵在植入后7-21天抵抗降解并引起杂合M1/M2巨噬细胞反应,并确认了一个原肿瘤M2d子集。Surgicel抵抗早期降解并引起明显的抗肿瘤M2a巨噬细胞反应。明胶海绵组皮下植入A549细胞和止血材料的小鼠肿瘤体积最大,总生存期(OS)最短,而Surgicel和生物层片组的体积最小,OS最长。因此,虽然明胶海绵在体外对A549细胞表现出细胞毒性,它们促进了体内A549细胞的生长,这与慢性M2d巨噬细胞反应有关。Surgicel和生物平台在体内抑制A549细胞生长,与慢性M2a巨噬细胞反应或急性Th1淋巴细胞反应有关。
Hemostatic materials are generally applied in surgical operations for cancer, but their effects on the growth and recurrence of tumors are unclear. Herein, three commonly used naturally derived hemostatic materials, gelatin sponge, Surgicel (oxidized regenerated cellulose), and biopaper (mixture of sodium hyaluronate and carboxymethyl chitosan), were cocultured with A549 human lung adenocarcinoma cells in vitro. Furthermore, the performance of hemostatic materials and the tumorigenicity of the materials with A549 cells were observed after subcutaneous implantation into BALB/c mice. The in vitro results showed that biopaper was dissolved quickly, with the highest cell numbers at 2 and 4 days of culture. Gelatin sponges retained their structure and elicited the least cell infiltration during the 2- to 10-day culture. Surgicel partially dissolved and supported cell growth over time. The in vivo results showed that biopaper degraded rapidly and elicited an acute Th1 lymphocyte reaction at 3 days after implantation, which was decreased at 7 days after implantation. The gelatin sponge resisted degradation and evoked a hybrid M1/M2 macrophage reaction at 7-21 days after implantation, and a protumor M2d subset was confirmed. Surgicel resisted early degradation and caused obvious antitumor M2a macrophage reactions. Mice subjected to subcutaneous implantation of A549 cells and hemostatic materials in the gelatin sponge group had the largest tumor volumes and the shortest overall survival (OS), while the Surgicel and the biopaper group had the smallest volumes and the longest OS. Therefore, although gelatin sponges exhibited cytotoxicity to A549 cells in vitro, they promoted the growth of A549 cells in vivo, which was related to chronic M2d macrophage reaction. Surgicel and biopaper inhibited A549 cell growth in vivo, which is associated with chronic M2a macrophage reaction or acute Th1 lymphocyte reaction.