He Chenlong, Yin Ming, Zhou Han, Qin Jingwen, Wu Shengming, Liu Huawei, Yu Xiaoyu, Chen Jing, Zhang Hongyi, Zhang Lin, Wang Yilong
State Key Laboratory of Cardiology and Medical Innovation Center, Shanghai East Hospital, The Institute for Biomedical Engineering & Nano Science, School of Medicine, Tongji University, Shanghai 200092, P. R. China.
The Institute for Translational Nanomedicine, Shanghai East Hospital, School of Medicine, Tongji University, Shanghai 200123, P. R. China.
ACS Nano. 2025 Jan 14;19(1):1713-1731. doi: 10.1021/acsnano.4c15647. Epub 2025 Jan 3.
Despite significant progress in skin wound healing, it is still a challenge to construct multifunctional bioactive dressings based on a highly aligned protein fiber coated hydrogel matrix for antifibrosis skin wound regeneration that is indistinguishable to native skin. In this study, a "dual-wheel-driven" strategy is adopted to modify the surface of methacrylated gelatin (GelMA) hydrogel with highly aligned magnetic nanocomposites-protein fiber assemblies (MPF) consisting of photothermal responsive antibacteria superparamagnetic nanocomposites-fibrinogen (Fg) complexes as the building blocks. Whole-phase healing properties of the modified hydrogel dressing, GelMA-MPF (GMPF), stem from the integration of Fg protein with RGD peptide activity decorated on the surface of the antibacterial magnetic nanoactuator, facilitating facile and reproducible dressing preparation by self-assembly and involving biochemical, morphological, and biophysical cues. Payload and substantial release of copper ions for catalytic production of nitric oxide (NO) from the fiber inorganic skeleton adsorbed by Fg molecules collectively regulate the proliferation, migration, reorganization, and transdifferentiation behavior of fibroblasts and fulfill antifibrosis in the process of skin wound healing and subcutaneous appendage regeneration. In full-thickness skin lesion mouse models, the complete regeneration of skin tissue with regenerated hair follicle cells and capillary blood vessels is realized in a temporally and spatially ordered manner.
尽管皮肤伤口愈合取得了显著进展，但构建基于高度排列的蛋白质纤维涂层水凝胶基质的多功能生物活性敷料以实现与天然皮肤无异的抗纤维化皮肤伤口再生，仍然是一项挑战。在本研究中，采用了一种“双轮驱动”策略，用由光热响应抗菌超顺磁性纳米复合材料-纤维蛋白原（Fg）复合物作为构建单元组成的高度排列的磁性纳米复合材料-蛋白质纤维组件（MPF）对甲基丙烯酸化明胶（GelMA）水凝胶表面进行改性。改性水凝胶敷料GelMA-MPF（GMPF）的全阶段愈合特性源于Fg蛋白与装饰在抗菌磁性纳米驱动器表面的具有RGD肽活性的整合，通过自组装促进了敷料制备的简便性和可重复性，并涉及生化、形态和生物物理线索。Fg分子吸附的纤维无机骨架上铜离子的负载和大量释放用于催化产生一氧化氮（NO），共同调节成纤维细胞的增殖、迁移、重组和转分化行为，并在皮肤伤口愈合和皮下附属器再生过程中实现抗纤维化。在全层皮肤损伤小鼠模型中，实现了具有再生毛囊细胞和毛细血管的皮肤组织以时间和空间有序的方式完全再生。
