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Open AccessArticle

3D Printing PLA/Gingival Stem Cells/ EVs Upregulate miR-2861 and -210 during Osteoangiogenesis Commitment

1
Department of Medical, Oral and Biotechnological Sciences, University “G. d’Annunzio”, 66100 Chieti-Pescara, Italy
2
IRCCS Centro Neurolesi “Bonino Pulejo”, 98124 Messina, Italy
3
CNR-National Research Council, Institute of Cell Biology and Neurobiology (IBCN), Monterotondo, 00015 Roma, Italy
*
Author to whom correspondence should be addressed.
These authors contributed equally to the paper as senior author.
Int. J. Mol. Sci. 2019, 20(13), 3256; https://doi.org/10.3390/ijms20133256
Received: 2 May 2019 / Revised: 14 June 2019 / Accepted: 27 June 2019 / Published: 2 July 2019
Bone tissue regeneration strategies require approaches that provide an osteogenic and angiogenic microenvironment able to drive the bone growth. Recently, the development of 3D printing biomaterials, including poly(lactide) (3D-PLA), enriched with mesenchymal stem cells (MSCs) and/or their derivatives, such as extracellular vesicles (EVs) has been achieving promising results. In this study, in vitro results showed an increased expression of osteogenic and angiogenic markers, as RUNX2, VEGFA, OPN and COL1A1 in the living construct 3D-PLA/human Gingival MSCs (hGMSCs)/EVs. Considering that EVs carry and transfer proteins, mRNA and microRNA into target cells, we evaluated miR-2861 and miR-210 expression related to osteoangiogenesis commitment. Histological examination of rats implanted with 3D-PLA/hGMSCs/EVs evidenced the activation of bone regeneration and of the vascularization process, confirmed also by MicroCT. In synthesis, an upregulation of miR-2861 and -210 other than RUNX2, VEGFA, OPN and COL1A1 was evident in cells cultured in the presence of the biomaterial and EVs. Then, these results evidenced that EVs may enhance bone regeneration in calvaria defects, in association with an enhanced vascularization offering a novel regulatory system in the osteoangiogenesis evolution. The application of new strategies to improve biomaterial engraftment is of great interest in the regenerative medicine and can represent a way to promote bone regeneration. View Full-Text
Keywords: microRNA; osteogenesis; angiogenesis; mesenchymal stem cells; extracellular vesicles; scaffold microRNA; osteogenesis; angiogenesis; mesenchymal stem cells; extracellular vesicles; scaffold
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Pizzicannella, J.; Diomede, F.; Gugliandolo, A.; Chiricosta, L.; Bramanti, P.; Merciaro, I.; Orsini, T.; Mazzon, E.; Trubiani, O. 3D Printing PLA/Gingival Stem Cells/ EVs Upregulate miR-2861 and -210 during Osteoangiogenesis Commitment. Int. J. Mol. Sci. 2019, 20, 3256.

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