State Key Laboratory of Fine Chemicals, School of Bioengineering, Dalian University of Technology, Dalian 116023, PR China.
State Key Laboratory of Fine Chemicals, School of Bioengineering, Dalian University of Technology, Dalian 116023, PR China; Central Laboratory, Longgang District People's Hospital of Shenzhen & The Third Affiliated Hospital (Provisional) of The Chinese University of Hong Kong, Shenzhen 518172, PR China; Guangdong Key Laboratory for Biomedical Measurements and Ultrasound Imaging, School of Biomedical Engineering, Health Science Center, Shenzhen University, Shenzhen 518060, PR China.
Mater Sci Eng C Mater Biol Appl. 2021 Dec;131:112497. doi: 10.1016/j.msec.2021.112497. Epub 2021 Oct 18.
Cell microenvironment is a collection of dynamic biochemical and biophysical cues which functions as the key factor in determining cell behavior. Encapsulating single cell into micrometer-scale hydrogels which mimics the cell microenvironment can be used for single cell analysis, cell therapies, and tissue engineering. Here, we developed a microfluidics-based platform to engineer the niche environment at single cell level using alginate microgels crosslinked by different metal ions to regulate stem cell behavior for bone regeneration. Specifically, we revealed that Ca in the engineered microenvironment promoted osteogenic differentiation of encapsulated stem cells and substantially accelerated the matrix mineralization compared to Srin vitro. However, the superior osteoinductive capacity of Ca compared with Sr led to comparable bone healing in a rat bone defect model. This attributed to Sr in microgels to inhibit the osteoclast activity and bone resorption after implantation. In summary, the present study demonstrates metal ions as a critical factor in the environmental cues to affect cell behavior and influence the efficacy of stem cell-based therapy in tissue regeneration, and provides new insights to engineer an expecting microenvironment for regenerative medicine.
细胞微环境是一组动态的生化和物理线索，它是决定细胞行为的关键因素。将单细胞包裹在模拟细胞微环境的微米级水凝胶中，可以用于单细胞分析、细胞治疗和组织工程。在这里，我们开发了一种基于微流控的平台，使用不同金属离子交联的藻酸盐微凝胶来构建单细胞水平的龛环境，以调节干细胞行为促进骨再生。具体来说，我们揭示了工程微环境中的 Ca 促进了包封干细胞的成骨分化，并与体外相比显著加速了基质矿化。然而，与 Sr 相比，Ca 具有优越的成骨诱导能力，导致在大鼠骨缺损模型中具有相当的骨愈合效果。这归因于微凝胶中的 Sr 抑制了植入后的破骨细胞活性和骨吸收。总之，本研究表明金属离子是影响细胞行为和影响基于干细胞的治疗在组织再生中疗效的环境线索中的一个关键因素，并为再生医学中构建预期的微环境提供了新的见解。
