Maria Giovanna Gandolfi1, Chiara Gardin2, Fausto Zamparini1, Letizia Ferroni2, Micaela Degli Esposti3, Greta Parchi1, Batur Ercan4, Lucia Manzoli5, Fabio Fava3, Paola Fabbri3, Carlo Prati6, Barbara Zavan2. 1. Laboratory of Biomaterials and Oral Pathology, School of Dentistry, Department of Biomedical and Neuromotor Sciences, University of Bologna, 40125 Bologna, Italy. 2. Medical Sciences Department, University of Ferrara, 44100 Ferrara, Italy. 3. Department of Civil, Chemical, Environmental and Materials Engineering, University of Bologna, 40136 Bologna, Italy. 4. Department of Metallurgical and Materials Engineering, 06800 Ankara, Turkey. 5. Cellular Signaling Laboratory, Institute of Human Anatomy, Department of Biomedical and Neuromotor Sciences, University of Bologna, 40126 Bologna, Italy. 6. Endodontic Clinical Section, School of Dentistry, Department of Biomedical and Neuromotor Sciences, University of Bologna, 40125 Bologna, Italy.
Abstract
Exosomes derived from mesenchymal stem cells are extracellular vesicles released to facilitate cell communication and function. Recently, polylactic acid (PLA), calcium silicates (CaSi), and dicalcium phosphate dihydrate (DCPD) have been used to produce bioresorbable functional mineral-doped porous scaffolds-through thermally induced phase separation technique, as materials for bone regeneration. The aim of this study was to investigate the effect of mineral-doped PLA-based porous scaffolds enriched with exosome vesicles (EVs) on osteogenic commitment of human adipose mesenchymal stem cells (hAD-MSCs). Two different mineral-doped scaffolds were produced: PLA-10CaSi-10DCPD and PLA-5CaSi-5DCPD. Scaffolds surface micromorphology was investigated by ESEM-EDX before and after 28 days immersion in simulated body fluid (HBSS). Exosomes were deposited on the surface of the scaffolds and the effect of exosome-enriched scaffolds on osteogenic commitment of hAD-MSCs cultured in proximity of the scaffolds has been evaluated by real time PCR. In addition, the biocompatibility was evaluated by direct-contact seeding hAD-MSCs on scaffolds surface-using MTT viability test. In both formulations, ESEM showed pores similar in shape (circular and elliptic) and size (from 10-30 µm diameter). The porosity of the scaffolds decreased after 28 days immersion in simulated body fluid. Mineral-doped scaffolds showed a dynamic surface and created a suitable bone-forming microenvironment. The presence of the mineral fillers increased the osteogenic commitment of hAD-MSCs. Exosomes were easily entrapped on the surface of the scaffolds and their presence improved gene expression of major markers of osteogenesis such as collagen type I, osteopontin, osteonectin, osteocalcin. The experimental scaffolds enriched with exosomes, in particular PLA-10CaSi-10DCPD, increased the osteogenic commitment of MSCs. In conclusion, the enrichment of bioresorbable functional scaffolds with exosomes is confirmed as a potential strategy to improve bone regeneration procedures.
Exosomes derived from mesenchymal stem cells are extracellular vesicles released to facilitate cell communication and function. Recently, pan class="Chemical">polylactic acid (PLA), calcium silicates (CaSi), and dicalcium phosphate dihydrate (DCPD) have been used to produce bioresorbable functional mineral-doped porous scaffolds-through thermally induced phase separation technique, as materials for bone regeneration. The aim of this study was to investigate the effect of mineral-doped PLA-based porous scaffolds enriched with exosome vesicles (EVs) on osteogenic commitment of human adipose mesenchymal stem cells (hAD-MSCs). Two different mineral-doped scaffolds were produced: PLA-10CaSi-10DCPD and PLA-5CaSi-5DCPD. Scaffolds surface micromorphology was investigated by ESEM-EDX before and after 28 days immersion in simulated body fluid (HBSS). Exosomes were deposited on the surface of the scaffolds and the effect of exosome-enriched scaffolds on osteogenic commitment of hAD-MSCs cultured in proximity of the scaffolds has been evaluated by real time PCR. In addition, the biocompatibility was evaluated by direct-contact seeding hAD-MSCs on scaffolds surface-using MTT viability test. In both formulations, ESEM showed pores similar in shape (circular and elliptic) and size (from 10-30 µm diameter). The porosity of the scaffolds decreased after 28 days immersion in simulated body fluid. Mineral-doped scaffolds showed a dynamic surface and created a suitable bone-forming microenvironment. The presence of the mineral fillers increased the osteogenic commitment of hAD-MSCs. Exosomes were easily entrapped on the surface of the scaffolds and their presence improved gene expression of major markers of osteogenesis such as collagen type I, osteopontin, osteonectin, osteocalcin. The experimental scaffolds enriched with exosomes, in particular PLA-10CaSi-10DCPD, increased the osteogenic commitment of MSCs. In conclusion, the enrichment of bioresorbable functional scaffolds with exosomes is confirmed as a potential strategy to improve bone regeneration procedures.
Entities:
Keywords:
bioresorbable scaffold; calcium silicates; exosome enriched scaffolds; exosomes; green bioplastics; human adipose mesenchymal stem cells (hAD-MSCs), polylactic acid scaffold; nanodelivery; natural nanovesicles; personalized regenerative medicine.; regenerative bone healing
Authors: W Benton Swanson; Zhen Zhang; Kemao Xiu; Ting Gong; Miranda Eberle; Ziqi Wang; Peter X Ma Journal: Acta Biomater Date: 2020-10-13 Impact factor: 8.947
Authors: Cristina Blanco-Elices; Enrique España-Guerrero; Miguel Mateu-Sanz; David Sánchez-Porras; Óscar Darío García-García; María Del Carmen Sánchez-Quevedo; Ricardo Fernández-Valadés; Miguel Alaminos; Miguel Ángel Martín-Piedra; Ingrid Garzón Journal: Materials (Basel) Date: 2020-04-04 Impact factor: 3.623