期刊
ACTA BIOMATERIALIA
卷 95, 期 -, 页码 285-296出版社
ELSEVIER SCI LTD
DOI: 10.1016/j.actbio.2019.01.057
关键词
Gelatin methacrylate (GelMA); Micro-hydrogel; Electrospray; hVEGF-secreting HUVEC; Hindlimb ischemia
资金
- Ministry of Science, ICT and Future Planning, Republic of Korea [NRF-2016R1E1A1A01943393, NRF-2017M3A9C6031786]
- Korea Health Technology R&D Project through the Korea Health Development Institute (KHIDI) - Ministry of Health & Welfare, Republic of Korea [HI14C1277]
Cell delivery systems based on micro-hydrogels may facilitate the long-term survival of cells upon transplantation. Micro-hydrogels may effectively support cell proliferation, attachment, and migration in ischemic environments. In this study, we report the fabrication of a gelatin methacrylate (GelMA)-based micro-hydrogel for efficient in vivo delivery of genetically engineered endothelial cells. Micro-hydrogels were initially processed via electrospraying of GelMA and alginate (ALG) mixtures (at different ratios) on to calcium chloride (CaCl2) solution. Electrospraying of the GelMA/ALG mixture resulted in the formation of a micro-hydrogel, owing to ALG crosslinking. Secondary crosslinking of GelMA with UV light and ALG hydrogel chelation using sodium citrate solution resulted in GelMA-based micro-hydrogel formation. We observed the angiogenic response of human umbilical vein endothelial cells (HUVECs) in GelMA concentration-dependent manner. The seeding of HUVECs engineered to express human vascular endothelial growth factor on to the GelMA micro-hydrogel and the subsequent transplantation of the micro-hydrogel into a hindlimb ischemia model effectively attenuated the ischemia condition. This facile and simple micro-hydrogel fabrication strategy may serve as a robust method to fabricate efficient cell carriers for various ischemic diseases. Statement of Significance For the therapeutic angiogenesis, it is important to provide the therapeutic cells with a carrier that could stabilize therapeutic cells and facilitate long-term survival of cells. Furthermore, it is also important to administer as many therapeutic cells as possible in a fixed volume. From these cues, we fabricated ECM-based micro-hydrogel produced by the high through-put system. And we intended to facilitate activation of therapeutic cells by coating the therapeutic cells onto the micro-hydrogel. In this manuscript, we fabricated methacrylate gelatin (GelMA) based micro-hydrogels using the electro-spraying method and coated HUVECs engineered to express hVEGF onto the micro-hydrogels. Then, we identified that GelMA concentration-dependent angiogenic response of HUVECs. Furthermore, we demonstrated that the VEGF secreting HUVEC-GelMA micro-hydrogels induced the restoration of blood flow and neovascularization in a hind-limb ischemia mouse model. These findings demonstrate that the high-throughput fabrication of ECM micro-hydrogels could be a novel platform to apply in neovascularization and tissue engineering. (C) 2019 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.
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