The Key Laboratory of Bioactive Materials, Ministry of Education, College of Life Science, Nankai University, Tianjin, 300071, China.
J Mater Chem B. 2020 Nov 11;8(43):9921-9932. doi: 10.1039/d0tb01593h.
Incorporating poly(lactic-co-glycolic) acid (PLGA) microparticles into human mesenchymal stem cells (hMSC) aggregates has shown promising application prospects. However, the acidic degradation products and burst release of PLGA microparticles still need to be ameliorated. In this study, the PLGA/chitosan-heparin (P/C-h) composite microparticles were successfully fabricated by integrating the double emulsion and microfluidic technology through the precise manipulation of the emulsion composition and flow rate of the two-phase in a flow-focusing chip. The P/C-h microparticles were highly monodispersed with a diameter of 23.45 ± 0.25 μm and shell-core structure of the PLGA encapsulated C-h complex, which were suitable for the fabrication of hMSC aggregates. When the mass ratio of PLGA to the C-h complex was optimized to 2 : 1, the pH of the leach liquor of P/C-h microparticles remained neutral. Compared with those of PLGA microparticles, the cytotoxicity and the initial burst release (loaded FGF-2 and VEGF) were both significantly reduced in P/C-h microparticles. Furthermore, the survival, stemness, as well as secretion and migration abilities of cells in hMSC aggregates incorporating P/C-h microparticles were also enhanced. In summary, the P/C-h composite microparticles prepared by the droplet microfluidic technique support the optimal biological and functional profile of the hMSC aggregates, which may facilitate the clinical applications of MSC-based therapy.
将聚（乳酸-共-乙醇酸）（PLGA）微球掺入人间充质干细胞（hMSC）聚集体中显示出了有前景的应用前景。然而，PLGA 微球的酸性降解产物和突释仍需要加以改善。在本研究中，通过在流聚焦芯片中精确控制乳液组成和两相的流速，成功地通过整合双重乳液和微流控技术制备了 PLGA/壳聚糖-肝素（P/C-h）复合微球。P/C-h 微球具有高度单分散性，粒径为 23.45 ± 0.25 μm，具有 PLGA 包封 C-h 复合物的核壳结构，适合 hMSC 聚集体的制备。当 PLGA 与 C-h 复合物的质量比优化至 2∶1 时，P/C-h 微球浸提液的 pH 值保持中性。与 PLGA 微球相比，P/C-h 微球的细胞毒性和初始突释（负载 FGF-2 和 VEGF）均显著降低。此外，掺入 P/C-h 微球的 hMSC 聚集体中的细胞的存活率、干性以及分泌和迁移能力也得到了增强。总之，通过液滴微流控技术制备的 P/C-h 复合微球支持 hMSC 聚集体的最佳生物学和功能特性，这可能有助于基于 MSC 的治疗的临床应用。
