Wen Xiao, Xi Kun, Tang Yu, Bian Jie, Qin Yu, Xiao Wanshu, Pan Tingzheng, Cheng Xiaoming, Ge Zili, Cui Wenguo
Department of Stomatology, The First Affiliated Hospital of Soochow University, 899 Pinghai Road, Suzhou, Jiangsu, 215006, P. R. China.
Department of Orthopaedics, Shanghai Key Laboratory for Prevention and Treatment of Bone and Joint Diseases, Shanghai Institute of Traumatology and Orthopaedics, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, 197 Ruijin 2nd Road, Shanghai, 200025, P. R. China.
Small. 2023 Apr;19(15):e2207030. doi: 10.1002/smll.202207030. Epub 2023 Jan 5.
The "double-edged sword" effect of macrophages under the influence of different microenvironments determines the outcome and prognosis of tissue injury. Accurate and stable reprogramming macrophages (Mφ) are the key to rapid wound healing. In this study, an immunized microsphere-engineered GelMA hydrogel membrane is constructed for oral mucosa treatment. The nanoporous poly(lactide-co-glycolide) (PLGA) microsphere drug delivery system combined with the photo-cross-linkable hydrogel is used to release the soybean lecithin (SL)and IL-4 complexes (SL/IL-4) sustainedly. In this way, it is realized effective wound fit, improvement of drug encapsulation, and stable triphasic release of interleukin-4 (IL-4). In both in vivo and in vitro experiments, it is demonstrated that the hydrogel membrane can reprogram macrophages in the microenvironment into M2Mφ anti-inflammatory types, thereby inhibiting the local excessive inflammatory response. Meanwhile, high levels of platelet-derived growth factor (PDGF) secreted by M2Mφ macrophages enhanced neovascular maturation by 5.7-fold, which assisted in achieving rapid healing of oral mucosa. These findings suggest that the immuno-engineered hydrogel membrane system can re-modulating the biological effects of Mφ, and potentiating the maturation of neovascularization, ultimately achieving the rapid repair of mucosal tissue. This new strategy is expected to be a safe and promising immunomodulatory biomimetic material for clinical translation.
在不同微环境影响下，巨噬细胞的“双刃剑”效应决定了组织损伤的结局和预后。准确且稳定地重编程巨噬细胞（Mφ）是伤口快速愈合的关键。在本研究中，构建了一种用于口腔黏膜治疗的免疫微球工程化明胶甲基丙烯酰基（GelMA）水凝胶膜。将纳米多孔聚（丙交酯-共-乙交酯）（PLGA）微球药物递送系统与可光交联水凝胶相结合，用于持续释放大豆卵磷脂（SL）和白细胞介素-4（IL-4）复合物（SL/IL-4）。通过这种方式，实现了有效的伤口贴合、药物包封率的提高以及白细胞介素-4（IL-4）的稳定三相释放。在体内和体外实验中均表明，该水凝胶膜可将微环境中的巨噬细胞重编程为M2型Mφ抗炎类型，从而抑制局部过度炎症反应。同时，M2型Mφ巨噬细胞分泌的高水平血小板衍生生长因子（PDGF）使新生血管成熟增强了5.7倍，这有助于实现口腔黏膜的快速愈合。这些发现表明，免疫工程化水凝胶膜系统可重新调节Mφ的生物学效应，并促进新生血管形成的成熟，最终实现黏膜组织的快速修复。这一新策略有望成为一种安全且有前景的免疫调节仿生材料用于临床转化。
