Thermo-sensitive hydrogel is preferable to liquid enema for topical treatments of ulcerative colitis (UC). Poly (ethylene oxide)-poly (propylene oxide)-poly-(ethylene oxide) copolymer branded as Poloxamer was commonly used as thermo-sensitive hydrogel material. However, the rapid erosion and poor mucosal adhesion compromised its practical application after rectal infusion. Herein, inspiring the mussel adhesion, dihydrocaffeic acid-modified poloxamer (P-DA) was designed to overcome these drawbacks. Series of P-DA polymers were synthesized by adjusting the feeding amounts of dihydrocaffeic acid (DA). P-DA polymers with suitable DA graft degree still showed the good thermo-sensitive properties. Moreover, P-DA hydrogels displayed the tougher mechanical strength than Poloxamer 407 hydrogel at the equivalent polymer concentration. Accordingly, in vitro erosion of P-DA hydrogel was significantly delayed in pH7.4 PBS (10 mM). Moreover, the stronger tissue adhesion for P-DA hydrogels was also reached. Epidermal growth factor (EGF) as model protein was delivered by P-DA hydrogels (P-DA-EGF). The stability of EGF was obviously improved by P-DA hydrogels. Moreover, the colonic retention of P-DA hydrogels was significantly prolonged in comparison with Poloxamer 407 hydrogel, leading to a higher mucosal absorption of EGF after their rectal infusion. In vivo animal studies showed that P-DA hydrogels also significantly improved the therapeutic effect of EGF on TNBS-induced ulcerative colitis rats. The colonic morphology and function of goblet cells were obviously restored by P-DA-EGF hydrogels. Moreover, the colonic mucosal healing was not orchestrated with the colonic fibrosis. The mechanism of the colonic mucosal barrier repairing for P-DA-EGF hydrogels was highly associated with polarizing macrophages from an inflammatory (M1) to anti-inflammatory (M2) phenotype. Collectively, the designed mussel-inspired P-DA hydrogel may be a promising system for the rectal delivery of therapeutic proteins.

对于局部治疗溃疡性结肠炎（UC），热敏性水凝胶优于液体灌肠剂。商标为泊洛沙姆的聚（环氧乙烷）-聚（环氧丙烷）-聚（环氧乙烷）共聚物通常用作热敏水凝胶材料。但是，快速输注和不良的粘膜黏附损害了直肠输注后的实际应用。在本文中，激发贻贝附着力的目的是设计二氢咖啡酸改性的泊洛沙姆（P-DA）来克服这些缺点。通过调节二氢咖啡酸（DA）的进料量来合成一系列P-DA聚合物。具有合适的DA接枝度的P-DA聚合物仍然显示出良好的热敏性能。此外，在相同的聚合物浓度下，P-DA水凝胶显示出比Poloxamer 407水凝胶更强的机械强度。因此，在pH7.4 PBS（10 mM）中，P-DA水凝胶的体外腐蚀显着延迟。此外，还达到了P-DA水凝胶的更强的组织粘附力。表皮生长因子（EGF）作为模型蛋白由P-DA水凝胶（P-DA-EGF）递送。P-DA水凝胶明显改善了EGF的稳定性。此外，与泊洛沙姆407水凝胶相比，P-DA水凝胶的结肠保留时间显着延长，导致直肠输注后EGF的黏膜吸收更高。体内动物研究表明，P-DA水凝胶还显着改善了EGF对TNBS所致溃疡性结肠炎大鼠的治疗作用。P-DA-EGF水凝胶可明显恢复杯状细胞的结肠形态和功能。此外，结肠粘膜愈合与结肠纤维化没有协调。P-DA-EGF水凝胶的结肠粘膜屏障修复机制与极化巨噬细胞从炎性（M1）到抗炎（M2）表型高度相关。总体而言，设计的贻贝启发式P-DA水凝胶可能是直肠输送治疗性蛋白质的有前途的系统。