Stem Cell Membrane-Coated Microribbon Scaffolds Induce Regenerative Innate and Adaptive Immune Responses in a Critical-Size Cranial Bone Defect Model.
Stem Cell Membrane-Coated Microribbon Scaffolds Induce Regenerative Innate and Adaptive Immune Responses in a Critical-Size Cranial Bone Defect Model.
复制标题
干细胞膜涂层微带支架在临界尺寸颅骨缺损模型中诱导再生先天性和适应性免疫反应。
DOI：
10.1002/adma.202208781
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发表时间：
2023
期刊：
影响因子：
--
通讯作者：
Yang,Fan
中科院分区：
文献类型：
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作者：
Su,Ni;Villicana,Cassandra;Barati,Danial;Freeman,Peyton;Luo,Ying;Yang,Fan
天然来源的细胞膜在功能化纳米颗粒以增强药物递送应用的生物界面功能方面显示出巨大的前景。然而，其功能化大孔支架以增强体内组织再生的潜力仍然未被探索。具有免疫调节功能的工程支架代表了组织再生的令人兴奋的策略，但主要限于软组织。临界尺寸的骨缺损不能自行愈合，适应性免疫细胞在支架介导的颅骨缺损愈合中的作用在很大程度上仍然未知。本文报道了间充质干细胞膜（MSCM）涂层微支架（µRB）通过靶向免疫调节治疗临界尺寸颅骨缺损。共聚焦成像和蛋白质组学分析用于确认成功的包被和表征细胞膜包被的组成。体外和体内实验表明，MSCM涂层可促进巨噬细胞（Mφ）向再生表型极化，诱导CD 8 + T细胞凋亡，并增强调节性T细胞分化。当与低剂量的BMP-2结合时，MSCM涂层进一步加速骨再生并抑制炎症。这些结果确立了细胞膜包被的微支架作为通过免疫调节治疗临界尺寸骨缺损的有前景的策略。该平台可广泛用于不同的细胞膜和支架，以增强多种组织类型的再生。
Naturally‐derived cell membranes have shown great promise in functionalizing nanoparticles to enhance biointerfacing functions for drug delivery applications. However, its potential for functionalizing macroporous scaffolds to enhance tissue regeneration in vivo remains unexplored. Engineering scaffolds with immunomodulatory functions represents an exciting strategy for tissue regeneration but is largely limited to soft tissues. Critical‐sized bone defects cannot heal on their own, and the role of adaptive immune cells in scaffold‐mediated healing of cranial bone defects remains largely unknown. Here, mensenchymal stem cell membrane (MSCM)‐coated microribbon (µRB) scaffolds for treating critical size cranial bone defects via targeting immunomodulation are reported. Confocal imaging and proteomic analyses are used to confirm successful coating and characterize the compositions of cell membrane coating. It is demonstrated that MSCM coating promotes macrophage (Mφ) polarization toward regenerative phenotype, induces CD8+ T cell apoptosis, and enhances regulatory T cell differentiation in vitro and in vivo. When combined with a low dosage of BMP‐2, MSCM coating further accelerates bone regeneration and suppresses inflammation. These results establish cell membrane‐coated microribbon scaffolds as a promising strategy for treating critical size bone defects via immunomodulation. The platform may be broadly used with different cell membranes and scaffolds to enhance regeneration of multiple tissue types.