Terasaki Institute for Biomedical Innovation (TIBI), 1018 Westwood Blvd, Los Angeles, California, USA.
Department of Materials Science and Engineering, Pohang University of Science and Technology (POSTECH), Pohang, Gyeongbuk, 37673, Republic of Korea.
Acta Biomater. 2024 Jan;173:231-246. doi: 10.1016/j.actbio.2023.10.026. Epub 2023 Oct 28.
Enterocutaneous fistula (ECF) is a severe medical condition where an abnormal connection forms between the gastrointestinal tract and skin. ECFs are, in most cases, a result of surgical complications such as missed enterotomies or anastomotic leaks. The constant leakage of enteric and fecal contents from the fistula site leads to skin breakdown and increases the risk of infection. Despite advances in surgical techniques and postoperative management, ECF accounts for significant mortality rates, estimated between 15-20%, and causes debilitating morbidity. Therefore, there is a critical need for a simple and effective method to seal and heal ECF. Injectable hydrogels with combined properties of robust mechanical properties and cell infiltration/proliferation have the potential to block and heal ECF. Herein, we report the development of an injectable nanoengineered adhesive hydrogel (INAH) composed of a synthetic nanosilicate (Laponite) and a gelatin-dopamine conjugate for treating ECF. The hydrogel undergoes fast cross-linking using a co-injection method, resulting in a matrix with improved mechanical and adhesive properties. INAH demonstrates appreciable blood clotting abilities and is cytocompatible with fibroblasts. The adhesive properties of the hydrogel are demonstrated in adhesion models with skin and arteries, where the volume stability in the hydrated internal environment facilitates maintaining strong adhesion. assessments reveal that the INAH is biocompatible, supporting cell infiltration and extracellular matrix deposition while not forming fibrotic tissue. These findings suggest that this INAH holds promising translational potential for sealing and healing ECF.
肠外瘘（ECF）是一种严重的医学病症，其特征是胃肠道与皮肤之间形成异常连接。在大多数情况下，ECF 是手术并发症的结果，例如肠切开术或吻合口漏的遗漏。肠内容物和粪便从瘘口不断泄漏会导致皮肤破裂，并增加感染的风险。尽管手术技术和术后管理有所进步，但 ECF 仍导致相当高的死亡率，估计在 15-20%之间，并导致严重的发病率。因此，迫切需要一种简单有效的方法来封闭和治愈 ECF。具有强大机械性能和细胞浸润/增殖综合特性的可注射水凝胶有可能阻断和治愈 ECF。在此，我们报告了一种可注射纳米工程黏附水凝胶（INAH）的开发，该水凝胶由合成纳米硅酸盐（Laponite）和明胶-多巴胺缀合物组成，用于治疗 ECF。该水凝胶通过共注射方法快速交联，形成具有改善的机械和黏附性能的基质。INAH 表现出相当好的凝血能力，并且与成纤维细胞相容。水凝胶的黏附性能在与皮肤和动脉的黏附模型中得到了证明，其中在水合内部环境中的体积稳定性有助于保持强黏附。评估表明，INAH 具有生物相容性，支持细胞浸润和细胞外基质沉积，而不会形成纤维组织。这些发现表明，这种 INAH 具有封闭和治愈 ECF 的潜在转化应用前景。
