自交联壳聚糖水凝胶膜通过氧化 CNC-AgNPs 稳定的 Pickering 乳液增强递送槲皮素加速全厚度皮肤创面组织再生。

BACKGROUND: The non-toxic self-crosslinked hydrogel films designed from biocompatible materials allow for controlled drug release and have gathered remarkable attention from healthcare professionals as wound dressing materials. Thus, in the current study the chitosan (CS) film is infused with oil-in-water Pickering emulsion (PE) loaded with bioactive compound quercetin (Qu) and stabilized by dialdehyde cellulose nanocrystal-silver nanoparticles (DCNC-AgNPs). The DCNC-AgNPs play a dual role in stabilizing PE and are involved in the self-crosslinking with CS films. Also, this film could combine the advantage of the controlled release and synergistic wound-healing effect of Qu and AgNPs. RESULTS: The DCNC-AgNPs were synthesized using sodium periodate oxidation of CNC. The DCNC-AgNPs were used to stabilize oil-in-water PE loaded with Qu in its oil phase by high speed homogenization. Stable PEs were prepared by 20% v/v oil: water ratio with maximum encapsulation of Qu in the oil phase. The Qu-loaded PE was then added to CS solution (50% v/v) to prepare self-crosslinked films (CS-PE-Qu). After grafting CS films with PE, the surface and cross-sectional SEM images show an inter-penetrated network within the matrix between DCNC and CS due to the formation of a Schiff base bond between the reactive aldehyde groups of DCNC-AgNPs and amino groups of CS. Further, the addition of glycerol influenced the extensibility, swelling ratio, and drug release of the films. The fabricated CS-PE-Qu films were analyzed for their wound healing and tissue regeneration potential using cell scratch assay and full-thickness excisional skin wound model in mice. The as-fabricated CS-PE-Qu films showed great biocompatibility, increased HaCat cell migration, and promoted collagen synthesis in HDFa cells. In addition, the CS-PE-Qu films exhibited non-hemolysis and improved wound closure rate in mice compared to CS, CS-Qu, and CS-blank PE. The H&E staining of the wounded skin tissue indicated the wounded tissue regeneration in CS-PE-Qu films treated mice. CONCLUSION: Results obtained here confirm the wound healing benefits of CS-PE-Qu films and project them as promising biocompatible material and well suited for full-thickness wound healing in clinical applications.

背景：由生物相容性材料设计的无毒自交联水凝胶薄膜允许控制药物释放，并作为伤口敷料材料引起了医疗保健专业人员的极大关注。因此，在本研究中，壳聚糖（CS）薄膜中注入了负载有生物活性化合物槲皮素（Qu）的油包水 Pickering 乳液（PE），并由二醛纤维素纳米晶体-银纳米颗粒（DCNC-AgNPs）稳定。DCNC-AgNPs 发挥稳定 PE 的双重作用，并参与 CS 薄膜的自交联。此外，该薄膜可以结合 Qu 和 AgNPs 控制释放和协同伤口愈合作用的优势。

结果：通过使用高碘酸钠氧化 CNC 合成了 DCNC-AgNPs。使用 DCNC-AgNPs 通过高速匀浆将 Qu 负载在油相中稳定油包水 PE。以 20%v/v 的油：水比例制备稳定的 PE，最大程度地将 Qu 包埋在油相中。然后将负载 Qu 的 PE 添加到 CS 溶液（50%v/v）中以制备自交联薄膜（CS-PE-Qu）。用 PE 接枝 CS 薄膜后，表面和横截面 SEM 图像显示由于 DCNC-AgNPs 的反应性醛基与 CS 的氨基之间形成席夫碱键，在基质内 DCNC 与 CS 之间形成互穿网络。此外，甘油的添加影响了薄膜的拉伸性、溶胀比和药物释放。使用细胞划痕试验和小鼠全层皮肤切口模型分析制备的 CS-PE-Qu 薄膜的伤口愈合和组织再生潜力。所制备的 CS-PE-Qu 薄膜表现出良好的生物相容性，增加了 HaCat 细胞的迁移，并促进了 HDFa 细胞中的胶原蛋白合成。此外，与 CS、CS-Qu 和 CS-空白 PE 相比，CS-PE-Qu 薄膜在小鼠中表现出非溶血和提高的伤口闭合率。受伤皮肤组织的 H&E 染色表明接受 CS-PE-Qu 薄膜治疗的小鼠的受伤组织再生。

结论：这里获得的结果证实了 CS-PE-Qu 薄膜的伤口愈合益处，并将其作为有前途的生物相容性材料进行预测，非常适合临床应用中的全层伤口愈合。