Du Liuyi, Zhang Xu, Huang Lei, Yang Mingxi, Zhang Wenbin, Xu Jiaqi, Liu Junguang, Xie Wangni, Zhang Xue, Liu Kexuan, Zhai Wenhao, Wen Linlin, Zhang Boya, Ye Rongrong, Liu Lijun, Wang Huan, Sun Hongchen, Li Daowei
Jilin Provincial Key Laboratory of Tooth Development and Bone Remodeling, Hospital of Stomatology, Jilin University, Changchun, 130021, PR China.
The Affiliated Stomatological Hospital of Soochow University, Suzhou Stomatological Hospital, Soochow University, Suzhou, 215000, PR China.
Mater Today Bio. 2025 Feb 11;31:101572. doi: 10.1016/j.mtbio.2025.101572. eCollection 2025 Apr.
Effective immune homeostasis modulation and re-epithelialization promotion are crucial for accelerating burn wound healing. Cell migration is fundamental to re-epithelialization, with epithelial-mesenchymal transition (EMT) as a key mechanism. A sustained inflammatory environment or impaired macrophage transition to M2 phenotype can hinder pro-resolving cytokine activation, further delaying the recruitment, migration, and re-epithelialization of epidermal cells to the injury site, ultimately compromising wound healing. Herein, the bioactive flavonol quercetin is transformed into pharmacologically active carbonized polymer dots (Qu-CDs) spray with high water dispersibility, permeability and biocompatibility for full-thickness skin burns treatment. Qu-CDs spray can efficiently initiate macrophage reprogramming and promote the transition of macrophages from M1 to M2 phenotype, modulating immune responses and facilitating the shift from the inflammatory phase to re-epithelialization. Additionally, Qu-CDs spray can promote cell migration and re-epithelialization of wound edge epithelial cells by inducing an EMT process without growth factors, further accelerating the reconstruction of the normal epidermal barrier. Mechanistically, Qu-CDs spray activates the smad1/5 signaling pathway for promoting the EMT phenotype of wound edge epithelial cells. Overall, this study facilitates the construction of novel spray dosage form of pharmacologically active carbonized polymer dots with desired bioactivities for effective wound healing.
有效的免疫稳态调节和促进再上皮化对于加速烧伤创面愈合至关重要。细胞迁移是再上皮化的基础，上皮-间质转化（EMT）是关键机制。持续的炎症环境或巨噬细胞向M2表型的转变受损会阻碍促分解细胞因子的激活，进一步延迟表皮细胞向损伤部位的募集、迁移和再上皮化，最终影响伤口愈合。在此，具有生物活性的黄酮醇槲皮素被转化为具有高水分散性、渗透性和生物相容性的药理活性碳化聚合物点（Qu-CDs）喷雾剂，用于全层皮肤烧伤治疗。Qu-CDs喷雾剂可有效启动巨噬细胞重编程，促进巨噬细胞从M1向M2表型转变，调节免疫反应，促进从炎症期向再上皮化的转变。此外，Qu-CDs喷雾剂可通过在无生长因子的情况下诱导EMT过程，促进伤口边缘上皮细胞的迁移和再上皮化，进一步加速正常表皮屏障的重建。机制上，Qu-CDs喷雾剂激活smad1/5信号通路，促进伤口边缘上皮细胞的EMT表型。总体而言，本研究有助于构建具有所需生物活性的新型药理活性碳化聚合物点喷雾剂剂型，以实现有效的伤口愈合。
