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Chemically induced hypoxia by dimethyloxalylglycine(DMOG)-loaded nanoporous silica nanoparticles supports endothelial tube formation by sustained VEGF release from adipose tissue-derived stem cells

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Regenerative Biomaterials 2021年第5期8卷 63-74页

作者： Sarah Zippusch Karen FWBesecke Florian Helms Melanie Klingenberg Anne Lyons Peter Behrens Axel Haverich mathias wilhelmi Nina Ehlert Ulrike Boer Lower Saxony Centre for Biomedical Engineering Implant Research and Development(NIFE)Hannover Medical SchoolStadtfelddamm 3430625 HannoverGermany Division for Cardiac Thoracic-Transplantation-and Vascular SurgeryHannover Medical SchoolCarl-Neuberg-Straße 130625 HannoverGermany Institute of Inorganic Chemistry Leibniz University HannoverCallinstraße 930167 HannoverGermany Cluster of Excellence Hearing4all Carl-von-Ossietzky-Straße 9-1126129 OldenburgGermany Department of Vascular-and Endovascular Surgery St.Bernward HospitalTreibestraße 931134 HildesheimGermany

Inadequate vascularization leading to insufficient oxygen and nutrient supply in deeper layers of bioartificial tissues remains a limitation in current tissue engineering approaches to which prevascularization offers a promising *** triggering pre-vascularization by enhanced vascular endothelial growth factor(VEGF)expression can be induced chemically by dimethyloxalylglycine(DMOG).Nanoporous silica nanoparticles(NPSNPs,or mesoporous silica nanoparticles,MSNs)enable sustained delivery of molecules and potentially release DMOG allowing a durable capillarization of a *** we evaluated the effects of soluble DMOG and DMOG-loaded NPSNPs on VEGF secretion of adipose tissue-derived stem cells(ASC)and on tube formation by human umbilical vein endothelial cells(HUVEC)-ASC *** doses of 100 mM and 500 mM soluble DMOG on ASC resulted in 3-to 7-fold increased VEGF levels on day 9(P<0.0001).Same doses of DMOG-NPSNPs enhanced VEGF secretion 7.7-fold(P<0.0001)which could be maintained until day 12 with 500 mM *** fibrin-based tube formation assays,100 mM DMOG-NPSNPs had inhibitory effects whereas 50 mM significantly increased tube length,area and number of junctions transiently for 4 ***,DMOG-NPSNPs supported endothelial tube formation by upregulated VEGF secretion from ASC and thus display a promising tool for prevascularization of tissue-engineered *** studies will evaluate their effect in hydrogels under perfusion.

关键词： pre-vascularization tissue engineering adipose tissue-derived stem cells dimethyloxalylglycine nanoporous silica nanoparticles

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