Collaborative Innovation Center of Technology and Equipment for Biological Diagnosis and Therapy in Universities of Shandong, Institute for Advanced Interdisciplinary Research (iAIR), University of Jinan, Jinan, 250022, P. R. China.
State Key Laboratory of Crystal Materials, Shandong University, Jinan, 250100, P. R. China.
Small. 2022 Jul;18(26):e2202485. doi: 10.1002/smll.202202485. Epub 2022 May 28.
Mesenchymal stem cells (MSCs) have been recognized as one of the most promising pharmaceutical multipotent cells, and a key step for their wide application is to safely and efficiently regulate their activities. Various methods have been proposed to regulate the directional differentiation of MSCs during tissue regeneration, such as nanoparticles and metal ions. Herein, nanoscale zeolitic imidazolate framework-8 (ZIF-8), a Zn-based metal-organic framework, is modified to direct MSCs toward an osteoblast lineage. Specifically, ZIF-8 nanoparticles are encapsulated using stem cell membranes (SCMs) to mimic natural molecules and improve the biocompatibility and targeted ability toward MSCs. SCM/ZIF-8 nanoparticles adjust the sustained release of Zn , and promote their specific internalization toward MSCs. The internalized SCM/ZIF-8 nanoparticles show excellent biocompatibility, and increase MSCs' osteogenic potentials. Moreover, RNA-sequencing results elucidate that the activated cyclic adenosine 3,5-monophosphate (cAMP)-PKA-CREB signaling pathway can be dominant in accelerating osteogenic differentiation. In vivo, SCM/ZIF-8 nanoparticles greatly promote the formation of new bone tissue in the femoral bone defect detected by 3D micro-CT, hematoxylin and eosin staining, and Masson staining after 4 weeks. Overall, the SCM-derived ZIF-8 nanostructures achieve the superior targeting ability, biocompatibility, and enhanced osteogenesis, providing a constructive design for tissue repair.
间充质干细胞（MSCs）已被认为是最有前途的药物多能细胞之一，其广泛应用的关键步骤是安全有效地调节其活性。已经提出了各种方法来调节组织再生过程中 MSC 的定向分化，例如纳米粒子和金属离子。在此，纳米级沸石咪唑酯骨架-8（ZIF-8），一种基于 Zn 的金属有机骨架，经过修饰后可引导 MSC 向成骨细胞系分化。具体而言，ZIF-8 纳米颗粒被干细胞膜（SCM）包裹，以模拟天然分子并提高 MSC 的生物相容性和靶向能力。SCM/ZIF-8 纳米颗粒可调节 Zn 的持续释放，并促进其向 MSC 的特异性内化。内化的 SCM/ZIF-8 纳米颗粒具有出色的生物相容性，并增强了 MSC 的成骨潜能。此外，RNA 测序结果表明，激活的环腺苷酸 3,5-单磷酸（cAMP）-蛋白激酶 A-CREB 信号通路可在加速成骨分化中起主导作用。在体内，SCM/ZIF-8 纳米颗粒在 4 周后通过 3D 微 CT、苏木精和伊红染色以及 Masson 染色检测到股骨骨缺损中大大促进了新骨组织的形成。总体而言，源自 SCM 的 ZIF-8 纳米结构实现了优越的靶向能力、生物相容性和增强的成骨作用，为组织修复提供了建设性的设计。
