Brown Mika, Okuyama Hideaki, Li Ling, Yang Zhen, Li Jianyu, Tabrizian Maryam, Li-Jessen Nicole Y K
Department of Biomedical Engineering, McGill University, Room 316 Duff Medical Building, 3775 Rue University, Montréal, QC, H3A 2B4, Canada.
Department of Otolaryngology-Head and Neck Surgery, Uji Tokushukai Medical Center, 145, Makishima-cho, Uji, Kyoto, 611-0041, Japan.
Biomaterials. 2026 Feb;325:123590. doi: 10.1016/j.biomaterials.2025.123590. Epub 2025 Aug 5.
Current injectable biomaterials for vocal fold disorders suffer from fast degradation and require frequent re-injection. Decellularized extracellular matrix (dECM) hydrogels are a tissue-derived, injectable biomaterial with intrinsic regenerative capacity. However, dECM hydrogels often exhibit mechanical instability and share the same problems with degradation as existing vocal fold biomaterials. In this work, we developed a composite dECM-alginate hydrogel with bioorthogonal click tetrazine ligation with improved stability, biocompatibility and regenerative capacity. dECM was extracted from two sources: tissue-specific vocal fold mucosa and scalable small intestinal submucosa for comparative analysis. Click dECM hydrogels from both sources were tunable and matched mechanical properties of native human vocal folds. The click dECM hydrogels showed capacity to resist contraction and modulate bioactive molecule secretion by fibroblasts, as well as stimulate the initial endothelial cell elongation phase of vasculogenesis. When injected subcutaneously into rats, both gels exhibit a strong initial immune response, followed by integration with the surrounding tissue by day 21. Overall, our click dECM hydrogels showed improved stability over previous dECM hydrogels and their performance was independent of tissue source.
目前用于声带疾病的可注射生物材料存在快速降解的问题，需要频繁重新注射。脱细胞细胞外基质（dECM）水凝胶是一种源自组织的可注射生物材料，具有内在的再生能力。然而，dECM水凝胶通常表现出机械不稳定性，并且与现有的声带生物材料存在相同的降解问题。在这项工作中，我们开发了一种具有生物正交点击四嗪连接的复合dECM-藻酸盐水凝胶，其稳定性、生物相容性和再生能力得到了改善。dECM从两个来源提取：组织特异性声带黏膜和可扩展的小肠黏膜下层用于比较分析。来自这两个来源的点击dECM水凝胶都是可调谐的，并且与天然人类声带的机械性能相匹配。点击dECM水凝胶显示出抵抗收缩和调节成纤维细胞生物活性分子分泌的能力，以及刺激血管生成的初始内皮细胞伸长阶段的能力。当皮下注射到大鼠体内时，两种凝胶都表现出强烈的初始免疫反应，随后在第21天与周围组织整合。总体而言，我们的点击dECM水凝胶比以前的dECM水凝胶具有更高的稳定性，并且其性能与组织来源无关。
