载有肝素的可降解温度敏感水凝胶可有效防止术后组织粘连,ACS Biomaterials Science & Engineering

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载有肝素的可降解温度敏感水凝胶可有效防止术后组织粘连
ACS Biomaterials Science & Engineering ( IF 5.4 ) Pub Date : 2023-05-14 , DOI: 10.1021/acsbiomaterials.3c00017
Puxin Lang ₁ , Tiantian Liu ₁ , Shiqi Huang ₁ , Zhaojie Zhou ₁ , Mengxing Zhang ₁ , Yunzhu Lin _{2,

3} , Qin He _{3,

4} , Yuqin Yao ₄ , Zhenmi Liu ₂ , Ling Zhang _{1,

2,

4}

Affiliation

手术后可能会发生组织粘连，严重的组织粘连会导致严重的并发症。医用水凝胶可以作为物理屏障应用于手术部位，以防止组织粘连。出于实际原因，人们非常需要可涂抹、可降解和可自我修复的凝胶。为了满足这些要求，我们将羧甲基壳聚糖 (CMCS) 应用于基于泊洛沙姆的水凝胶，以生成低泊洛沙姆₃₃₈ (P ₃₃₈ ) 含量的凝胶，该凝胶在冰箱温度下显示出低粘度，在体温下具有更高的机械强度。还添加了一种有效的粘附抑制剂肝素来构建 P ₃₃₈/CMCS-肝素复合水凝胶（PCHgel）。PCHgel 在 20 °C 以下呈可流动液体，在因温度变化而扩散到受损组织表面时可迅速转变为凝胶。CMCS 的引入使水凝胶能够在受伤位置形成稳定的自愈屏障，并在伤口愈合期间缓慢释放肝素，然后在约 14 天后降解。最终，PCHgel 显着降低了模型大鼠的组织粘附，并显示出比不含肝素的 P ₃₃₈ /CMCS 凝胶更高的效率。其粘附抑制机制得到验证，并显示出良好的生物安全性。因此，PCHgel具有疗效高、安全性好、使用方便等特点，具有良好的临床转化潜力。

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Degradable Temperature-Sensitive Hydrogel Loaded with Heparin Effectively Prevents Post-Operative Tissue Adhesions

Tissue adhesions could occur following surgeries, and severe tissue adhesions can lead to serious complications. Medical hydrogels could be applied at surgical sites as a physical barrier to prevent tissue adhesion. For practical reasons, spreadable, degradable, and self-healable gels are highly demanded. To meet these requirements, we applied carboxymethyl chitosan (CMCS) to poloxamer-based hydrogels to generate low Poloxamer₃₃₈ (P₃₃₈) content gels displaying low viscosity at refrigerator temperature and improved mechanical strength at body temperature. Heparin, an effective adhesion inhibitor, was also added to construct P₃₃₈/CMCS-heparin composite hydrogel (PCHgel). PCHgel presents as a flowable liquid below 20 °C and could rapidly transform into gel when spread on the surface of damaged tissue due to temperature change. The introduction of CMCS enabled hydrogels to form a stable self-healable barrier at injured positions and slowly release heparin during the wound healing period before being degraded after ∼14 days. Ultimately, PCHgel significantly reduced tissue adhesion in model rats and displayed higher efficiency than P₃₃₈/CMCS gel without heparin. Its adhesion suppression mechanism was verified, and it also displayed good biosafety. Therefore, PCHgel showed good clinical transformation potential with high efficacy, good safety, and ease of use.

更新日期：2023-05-14

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