A multifunctional neuromodulation platform utilizing Schwann cell-derived exosomes orchestrates bone microenvironment via immunomodulation, angiogenesis and osteogenesis.
A multifunctional neuromodulation platform utilizing Schwann cell-derived exosomes orchestrates bone microenvironment via immunomodulation, angiogenesis and osteogenesis.
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利用雪旺细胞来源的外泌体的多功能神经调节平台通过免疫调节、血管生成和成骨来协调骨微环境
DOI：
10.1016/j.bioactmat.2022.10.018
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发表时间：
2023-05
影响因子：
18.9
通讯作者：
Xia, Juan
中科院分区：
文献类型：
--
作者：
Hao, Zhichao;Ren, Lin;Zhang, Zhen;Yang, Zaiwu;Wu, Shujie;Liu, Gen;Cheng, Bin;Wu, Jun;Xia, Juan
关键词：
最近的证据强调了多方面的生物学需求，以重述骨再生的骨微环境。在骨组织工程中，神经化具有实现多系统调节的巨大潜力。然而，暂时涉及所有关键的骨修复步骤的神经策略还没有报道。在本研究中，我们报道了水凝胶包裹的雪旺细胞来源的外切体(SC Exo)。这种缓释SC Exo系统通过促进体内的神经支配、免疫调节、血管形成和成骨，显著促进了骨再生。此外，体外实验结果进一步证实，该体系能显著诱导巨噬细胞M2极化、HUVECs管状形成和BMSCs成骨分化。此外，通过上调转化生长因子-β1/Smad2/3信号通路，促进骨髓间充质干细胞成骨。综上所述，成功构建了一种新型的无细胞、易于制备的SC Exo神经工程，通过协调整个骨愈合微环境来促进骨再生，为组织工程和骨缺损的临床治疗提供了新的策略。本研究的重点是基于骨愈合微环境的骨组织工程的设计。SC Exosome Platform通过免疫调节、血管生成和成骨来暂时调节骨愈合过程。SC外切体的无细胞治疗为BTE的神经化和骨缺损的临床治疗提供了一种新的策略。
Recent evidence highlights multifaceted biological needs to recapitulate the bone microenvironment for bone regeneration. Neurotization has great potential for realizing multi-system modulations in bone tissue engineering (BTE). However, a neural strategy involving all the key bone repair steps temporally has not yet been reported. In this study, we reported the neural tissue engineering hydrogel-encapsulated Schwann cell-derived exosomes (SC Exo). This sustained-release SC Exo system prominently enhanced bone regeneration by promoting innervation, immunoregulation, vascularization, and osteogenesis in vivo. Moreover, the in vitro results further confirmed that this system significantly induced M2 polarization of macrophages, tube formation of HUVECs, and BMSCs osteogenic differentiation. Furthermore, BMSCs osteogenesis was promoted by upregulating the TGF-β1/SMAD2/3 signaling pathway. In summary, a novel cell-free and easily prepared SC Exo neural engineering was successfully developed to promote bone regeneration by orchestrating the entire bone healing microenvironment, which may provide a new strategy for tissue engineering and clinical treatment of bone defects. This study highlights the designing of bone tissue engineering (BTE) based on bone healing microenvironment. The SC exosomes platform regulates bone healing process temporally via immunomodulation, angiogenesis and osteogenesis. Cell free therapy with SC exosomes provides a new strategy for neurotization in BTE and clinical treatment of bone defects.
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