腹部粘连是术后常见的并发症，它会引起患者疼痛，增加再手术的风险。除了手术切断粘连组织，防粘连膜也常用于预防外科手术后发生的组织粘连，作为物理屏障，它可以将受伤的部位与相邻的组织或器官隔离而起到防粘连的作用。在各种材质的防粘连膜中，基于静电纺丝技术构建的纤维膜因其轻薄柔韧的质地、较好的机械性能，是一种理想的防粘连材料，受到广泛关注。然而，静电纺丝纤维膜仍存在防粘连效果有限等相关问题。因此，增强医用膜的防粘连效果，开发一种有效的静电纺丝防粘连产品仍是该领域研究工作的热点和难点。聚酯因具有良好的成纤性和力学性能，常用作构建防止腹部粘连的静电纺丝聚合物膜。然而，基于原位组织再生不同阶段的视角，由于缺乏材料-组织界面作用的生物活性，引起过度的炎症反应，导致防粘连和促进组织再生的效果有限。

本课题拟采用静电纺丝技术制备聚酯纤维膜，并且对其表面进行改性，提高防粘连效果。为了使纤维膜具有抗炎效果，进一步负载抗炎活性成分，制备生物活性防粘连膜。研究其对腹腔粘连的抑制作用并探索其机制，为防止腹腔粘连提供新型纤维膜材料。首先将通过静电纺丝制备聚 (丙交酯-己内酯) (PLCL) 纤维膜，表面浸渍甲基丙烯酸酰化明胶 (GelMA) 溶液，紫外光 (UV) 照射下，诱导形成水凝胶涂层，赋予静电纺丝膜良好的亲水性和生物活性。炎症与粘连组织的生成密切相关，本课题进一步将硫酸软骨素 (CS) 负载至聚(乳酸-羟基乙酸)共聚物poly(lactic-co-glycolic acid) (PLGA) 静电纺丝膜。抗炎活性材料的加入使PLGA静电纺丝膜具有良好的抗炎效果，可以调控损伤处过度的炎症，达到防止粘连的效果。体外实验中，测试静电纺丝膜的物理性能和细胞相容性；其次，构建SD大鼠腹壁损伤模型，利用静电纺丝膜预防腹腔粘连，通过大体观察、病理切片观察、免疫荧光染色、ELISA检测等分析腹腔粘连的程度，组织病理结构重建，纤溶系统的激活和免疫环境的调节，研究其抑制腹腔粘连形成的可能作用机理。

机械性能表征证明，PLCL/GelMA膜的的杨氏模量为0.81 ± 0.05 MPa，最大载荷为6.58 ± 1.02 N和拉伸失效应变为810.6 ± 90.63 %。对成纤维细胞无细胞毒性，具有良好的细胞相容性。大鼠腹腔防粘连效果表明，PLCL/GelMA膜显著上调组织型纤溶酶原激活剂 (t-PA) 的表达，下调纤溶酶原激活剂抑制剂-1 (PAI-1) 的产生，从而激活纤溶系统；另外，纤维膜促进MMP-9的分泌，减少ECM中胶原的沉积，抑制粘连组织的形成。另外，PLGA/CS膜提高了M2型巨噬细胞在炎症细胞中的比例，促进抗炎因子的分泌，减少促炎因子的分泌；同时，促进腹部损伤组织的修复。因此，PLGA/CS膜能够通过调控损伤组织中的炎症环境，降低过度的炎症反应，从而减少粘连组织的产生。

综上所述，静电纺丝膜表面明胶化或混合抗炎大分子是一种构建生物活性防粘连膜的有效方法。生物活性纤维膜为解决腹腔粘连这一临床实际问题提供了创新治疗策略，在再生医学领域具有广阔的应用前景。

Abdominal adhesions are a common postoperative complication that can cause pain in patients and increase the risk of re-operation. Besides surgical removal, anti-adhesion film serving as a medical barrier is used to prevent tissue adhesion after surgery, which can separate the injured area from adjacent tissues and organs. Among various biomaterials-based anti-adhesion films, fiber membranes constructed by electrospinning technology have received widespread attention in the field of anti-adhesion treatment due to their lightweight, flexible texture, and good mechanical properties, making them ideal anti-adhesion materials. However, the anti-adhesion effect of electrospun fiber membranes is still limited. Therefore, enhancing the anti-adhesion ability of medical membranes remains a great challenge. Polyester is commonly used to construct electrospun polymer films to prevent abdominal adhesions due to excellent fiber formation and mechanical properties. However, from the perspective of different stages of in situ tissue regeneration, the efficacy of anti-adhesion and pro-regeneration is limited due to the lack of biological activity at the material-tissue interface and the induction of excessive inflammatory response.

This project aims to use electrospinning technology to prepare fiber membranes and modify their surfaces to improve the outcome of anti-adhesion. Further, to render the membrane with anti-inflammation feature, anti-inflammatory ingredients were loaded into the anti-adhesion membrane. The inhibitory effect on abdominal adhesions by fibrious membranes was studied and related mechanism of action was explored. First, poly(lactide-co-caprolactone) (PLCL) electrospun fiber membrane was prepared and coated by GelMA solution containing photo-initiator. After being irradiated by ultraviolet light (UV), the surface hydrogel coating was formed to produce a composite membrane with favorable hydrophilicity and biological activity. Inflammation is closely related to the formation of adhesive tissue. Further, chondroitin sulfate (CS) was loaded into poly(lactic-co-glycolic acid) (PLGA) electrospun membranes. It was anticaipated that the addition of anti-inflammatory materials would eliminate the excessive inflammation at the wound to prevent adhesion. In vitro experiments including the characterization of physical performance and cell compatibility of electrospun membranes were studied. Second, abdominal adhesion models in SD rats were constructed to test the efficacy of electrospinning membranes. Macroscopic observation, pathological section observation, immunofluorescence staining, and ELISA detection were used to analyze the activation of fibrinolytic system and regulation of the immune environment. Then, the mechanism of abdominal adhesion prevention was examined.

It was found PLCL/GelMA film has good mechanical properties with the Young’s modulu of 0.81 ± 0.05 MPa, the maximum load of 6.58 ± 1.02 N and failure strain of 810.6 ± 90.63 %. In vitro cell compatibility indicated that the membrane showed no cytotoxicity to fibroblasts. PLCL/GelMA membrane significantly up-regulated the expression of tissue type plasminogen activator (t-PA), down-regulated the production of plasmin activator inhibitor-1 (PAI-1), activated the fibrinolytic system, and promoted the secretion of MMP-9. Thus, the deposition of collagen in ECM was decreased, inhibiting the formation of adhesive tissue. More importantly, PLGA/CS membrane increased the proportion of M2 macrophages in inflammatory cells, promoted the secretion of anti-inflammatory factors, and reduced the secretion of pro-inflammatory factors, while the injured abdominal wall was completely repaired after 21 days. By regulating the inflammatory environment in damaged tissues, excessive inflammatory reactions were reduced, thereby reducing the production of adhesive tissues.

Overall, surface gelatinization or intruding bioactive polymers to electrospun film is a promising approach for developing bioactive barrier for preventing postoperative abdominal adhesions. Bioactive fibrous membrane provides a new treatment strategy for abdominal adhesions, which has broad application prospects in regenerative medicine.