針對術後沾黏的預防：殼聚醣與硫酸化多醣抗沾黏膜的設計與應用

Abstract

術後沾黏為外科手術常見的併發症，可能導致慢性疼痛、腸阻塞，甚至需再次手術。然而，目前市售的抗沾黏產品如Seprafilm與Interceed，雖具備一定的物理屏障效果，卻常因機械性質不佳、效果有限或無法同時調控免疫反應而導致療效有限。因此，開發兼具穩定黏附性與生物功能性的抗沾黏材料，為術後併發症預防的重要課題。 本研究設計一種具不對稱結構之Janus雙層抗沾黏薄膜，作為手術後的物理屏障。此雙層薄膜之抗沾黏層以硫酸纖維素構成，利用其帶負電性質與帶正電的細胞因子進行中和，並結合其類肝素特性達到抗發炎特性，來減緩手術部位的發炎反應，以達到抗沾黏的效果；而沾黏層以殼聚醣為基底，考量其良好的生物相容性、生物可降解性及其官能基使其可以附著於組織表面，避免位移或脫落。此外，具胺基的陽離子特性，能有效與陰離子層形成穩定結構，經由層間界面離子交聯，維持層與層之間的穩定性。 在本研究中，通過傅立葉轉換紅外光譜、核磁共振光譜以及掃描式顯微鏡等儀器確認材料結構與雙層界面，並評估其機械性質以及黏附能力，進一步以蛋白吸附、細胞因子吸附與細胞貼附試驗探討材料表面之選擇性貼附行為，再透過溶血試驗與細胞毒性分析確認其血液與細胞相容性，確定此薄膜不會對生物造成毒性反應。最後藉由大鼠盲腸腹壁缺損模型來評分，並以病理切片與西方墨點法來驗證其在降低沾黏形成及抑制術後發炎方面的潛力。 綜合以上結果，此具不對稱設計之Janus薄膜不僅展現優異的物理屏障功能，結合主動生物調節。亦具備良好的組織相容性與生物活性，可以有效預防術後沾黏生成，具備作為腹部手術後抗沾黏材料的應用潛力。

Postoperative adhesions are a common complication of surgical procedures and can lead to chronic pain, bowel obstruction, and even the need for reoperation. However, commercially available anti-adhesive products, such as Seprafilm and Interceed, have a certain physical barrier effect, but their efficacy is often limited due to poor mechanical properties, limited effectiveness, or inability to modulate immune responses. Therefore, the development of anti-adhesive materials with stabilized adhesive properties and biofunctionality is an important issue in the prevention of postoperative complications. In this study, a Janus dual-layer anti-adhesion film with an asymmetric structure was developed to serve as a physical barrier after surgery. The anti-adhesive layer was composed of sulfated cellulose, which possesses negatively charged functional groups capable of neutralizing positively charged cytokines, thereby mitigating local inflammatory responses. Additionally, its heparin-mimetic properties confer anti-inflammatory effects, further enhancing its anti-adhesive performance. The adhesive layer was based on chitosan, chosen for its excellent biocompatibility, biodegradability, and functional groups that facilitate adhesion to tissue surfaces, thereby preventing displacement or detachment. Furthermore, the cationic nature of chitosan, attributed to its abundant amine groups, enables strong electrostatic interaction with the anionic sulfated cellulose layer. This interfacial ionic crosslinking promotes structural integrity and stability between the two layers. In this study, the structure and dual-layer interface of the fabricated film were characterized using Fourier-transform infrared (FT-IR) spectroscopy, nuclear magnetic resonance (NMR) spectroscopy, and scanning electron microscopy (SEM). Its mechanical properties and adhesion ability were also evaluated. To investigate the selective adhesion behavior of the film surface, protein adsorption, cytokine-binding, and cell attachment assays were performed. In addition, hemolysis testing and cytotoxicity analysis were conducted to assess the blood and cellular compatibility, confirming that the film did not elicit toxic responses. Finally, the anti-adhesion and anti-inflammatory potential of the film was validated using a rat cecum-abdominal wall defect model, supported by histological examination and Western blot analysis. In conclusion, the asymmetric design of the Janus film not only functions as an effective physical barrier but also integrates active biological modulation. It exhibits excellent tissue compatibility and bioactivity, effectively preventing postoperative adhesion formation. These characteristics underscore its strong potential for application as an anti-adhesion material following abdominal surgery.