Although engineered nanoparticles loaded with specific growth factors are used to regulate differentiation of stem cells, the low loading efficiency and biocompatibility are still great challenges in tissue repair. A nature-inspired biomimetic delivery system with targeted functions is attractive for enhancing cell activity and controlling cell fate. Herein, a stem cell membrane (SCM)-wrapped dexamethasone (DEX)-loaded zeolitic imidazolate framework-8 (ZIF-8) is constructed, which integrates the synthetic nanomaterials with native plasma membrane, to achieve efficient DEX delivery and DEX-mediated bone repair. The DEX@ZIF-8-SCM enables high DEX loading capacity, modulates the sustained release, and facilitates the specific uptake of mesenchymal stem cells (MSCs), owing to the porous property of ZIF-8 and the innate targeting capability of SCM. The endocytosed DEX@ZIF-8-SCM shows high cytocompatibility and greatly enhances the osteogenic differentiation of MSCs. Furthermore, RNA-sequencing data reveal that the phosphoinositide 3-kinase (PI3K)-Akt signaling pathways are activated and dominantly involved in the accelerated osteogenesis. In the bone defect model, the administrated DEX@ZIF-8-SCM exerts excellent biocompatibility and effectively promotes bone regeneration. Overall, the SCM-derived biomimetic nanoplatform achieves targeted delivery, excellent biosafety, and enhanced osteogenic differentiation and bone repair, which provides a new and valid strategy for treating various tissue injuries.
Keywords: biomimetic delivery; bone regeneration; mesenchymal stem cells; metal−organic frameworks; osteogenic differentiation.
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