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

Jacopo Pizzicannella,Tiziana Orsini,Placido Bramanti,Ilaria Merciaro,Emanuela Mazzon,Luigi Chiricosta,Francesca Diomede,Oriana Trubiani,Agnese Gugliandolo

doi:10.3390/ijms20133256

Jacopo Pizzicannella, Tiziana Orsini + Show 7 more

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https://doi.org/10.3390/ijms20133256

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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.

Highlights

The body is unable to repair and regenerate large area bone defects afterwards trauma, infection, surgical resections, and other systemic problems exert negative effects on the bone healing process [1]
We evaluated the regeneration of calvaria in rats transplanted with 3D printing PLA scaffold enriched with human Gingival mesenchymal stem cell (MSC) (hGMSCs) and/or extracellular vesicles (EVs)
3D-PLA has been analysed at MicroCT to define dimension features (Table 1) and observed via scanning electron microscopy (SEM) to define the surface morphology (Figure 1)

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Introduction

The body is unable to repair and regenerate large area bone defects afterwards trauma, infection, surgical resections, and other systemic problems exert negative effects on the bone healing process [1]. Starting from this consideration, the engineered tissue with different scaffolds for osteogenic repair has become one of the intriguing research fields over the past few years. A key role is reserved to fiber and pore sizes that may influence some cellular responses, including migration, proliferation, and differentiation [2,3] For these reasons, new biomaterials as bone substitutes able to induce minimal or no immune response and for encouraging implant/tissue interaction have been introduced. PLA is widely used in the field of regenerative medicine thanks to its good features, such as biodegradability, biocompatibility, thermal plasticity, and suitable mechanical effects [5]

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