Self-oxygenation of engineered living tissues orchestrates osteogenic commitment of mesenchymal stem cells.
Self-oxygenation of engineered living tissues orchestrates osteogenic commitment of mesenchymal stem cells.
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DOI：
10.1016/j.biomaterials.2023.122179
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发表时间：
2023-05
期刊：
影响因子：
14
通讯作者：
Shabir Hassan;Ting Wang;Kun Shi;Yike Huang;Mariely Urbina;Kaifeng Gan;Mo Chen;Niels G A Willemen;Haroon Kalam;E. Luna-Ceron;Berivan Çeçen;Gihan Daw Elbait;Jinghang Li;Luis Enrique García-Rivera;Melvin Gurian;Mudassir Meraj Banday;Kisuk Yang;M. C. Lee;Weida Zhuang;Castro Johnbosco;Oju Jeon;E. Alsberg;J. Leijten;S. Shin
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作者：
Shabir Hassan;Ting Wang;Kun Shi;Yike Huang;Mariely Urbina;Kaifeng Gan;Mo Chen;Niels G A Willemen;Haroon Kalam;E. Luna-Ceron;Berivan Çeçen;Gihan Daw Elbait;Jinghang Li;Luis Enrique García-Rivera;Melvin Gurian;Mudassir Meraj Banday;Kisuk Yang;M. C. Lee;Weida Zhuang;Castro Johnbosco;Oju Jeon;E. Alsberg;J. Leijten;S. Shin
充氧生物材料可以缓解缺氧应激、刺激血管化并改善细胞化植入物的植入。然而，产氧材料对组织形成的影响仍然很大程度上未知。在这里，我们研究了基于过氧化钙（CPO）的产氧微粒（OMP）在严重缺氧的微环境下对人间充质干细胞（hMSC）成骨命运的影响。为此，将 CPO 微胶囊化在聚己内酯中，生成具有延长释氧能力的 OMP。含有成骨诱导硅酸盐纳米粒子（SNP 水凝胶）、OMP（OMP 水凝胶）或 SNP 和 OMP（SNP/OMP 水凝胶）的明胶甲基丙烯酰（GelMA）水凝胶被设计用于比较研究它们对 hMSC 成骨命运的影响。 OMP 水凝胶在常氧和缺氧条件下都与改善成骨分化有关。大量 mRNAseq 分析表明，缺氧条件下的 OMP 水凝胶比缺氧或常氧条件下的 SNP/OMP 或 SNP 水凝胶更能调节成骨分化途径。皮下植入显示 SNP 水凝胶具有更强的宿主细胞侵袭能力，导致血管生成增加。此外，不同成骨因子的时间依赖性表达揭示了 OMP、SNP 和 SNP/OMP 水凝胶中 hMSC 的渐进分化。我们的工作表明，向水凝胶赋予 OMP 可以诱导、改善和引导功能性工程活组织的形成，这在组织再生和器官替代治疗等众多生物医学应用中具有潜力。
Oxygenating biomaterials can alleviate anoxic stress, stimulate vascularization, and improve engraftment of cellularized implants. However, the effects of oxygen-generating materials on tissue formation have remained largely unknown. Here, we investigate the impact of calcium peroxide (CPO)-based oxygen-generating microparticles (OMPs) on the osteogenic fate of human mesenchymal stem cells (hMSCs) under a severely oxygen deficient microenvironment. To this end, CPO is microencapsulated in polycaprolactone to generate OMPs with prolonged oxygen release. Gelatin methacryloyl (GelMA) hydrogels containing osteogenesis-inducing silicate nanoparticles (SNP hydrogels), OMPs (OMP hydrogels), or both SNP and OMP (SNP/OMP hydrogels) are engineered to comparatively study their effect on the osteogenic fate of hMSCs. OMP hydrogels associate with improved osteogenic differentiation under both normoxic and anoxic conditions. Bulk mRNAseq analyses suggest that OMP hydrogels under anoxia regulate osteogenic differentiation pathways more strongly than SNP/OMP or SNP hydrogels under either anoxia or normoxia. Subcutaneous implantations reveal a stronger host cell invasion in SNP hydrogels, resulting in increased vasculogenesis. Furthermore, time-dependent expression of different osteogenic factors reveals progressive differentiation of hMSCs in OMP, SNP, and SNP/OMP hydrogels. Our work demonstrates that endowing hydrogels with OMPs can induce, improve, and steer the formation of functional engineered living tissues, which holds potential for numerous biomedical applications, including tissue regeneration and organ replacement therapy.