Biohybrid Bovine Bone Matrix for Controlled Release of Mesenchymal Stem/Stromal Cell Lyosecretome: A Device for Bone Regeneration
SmartBone<sup>®</sup> (SB) is a biohybrid bone substitute advantageously proposed as a class III medical device for bone regeneration in reconstructive surgeries (oral, maxillofacial, orthopedic, and oncology). In the present study, a new strategy to improve SB osteoinductivity was devel...
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| Format: | Article |
| Language: | English |
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MDPI AG
2021-04-01
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| Series: | International Journal of Molecular Sciences |
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| Online Access: | https://www.mdpi.com/1422-0067/22/8/4064 |
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| author | Elia Bari Ilaria Roato Giuseppe Perale Filippo Rossi Tullio Genova Federico Mussano Riccardo Ferracini Marzio Sorlini Maria Luisa Torre Sara Perteghella |
| author_facet | Elia Bari Ilaria Roato Giuseppe Perale Filippo Rossi Tullio Genova Federico Mussano Riccardo Ferracini Marzio Sorlini Maria Luisa Torre Sara Perteghella |
| author_sort | Elia Bari |
| collection | DOAJ |
| description | SmartBone<sup>®</sup> (SB) is a biohybrid bone substitute advantageously proposed as a class III medical device for bone regeneration in reconstructive surgeries (oral, maxillofacial, orthopedic, and oncology). In the present study, a new strategy to improve SB osteoinductivity was developed. SB scaffolds were loaded with lyosecretome, a freeze-dried formulation of mesenchymal stem cell (MSC)-secretome, containing proteins and extracellular vesicles (EVs). Lyosecretome-loaded SB scaffolds (SBlyo) were prepared using an absorption method. A burst release of proteins and EVs (38% and 50% after 30 min, respectively) was observed, and then proteins were released more slowly with respect to EVs, most likely because they more strongly adsorbed onto the SB surface. In vitro tests were conducted using adipose tissue-derived stromal vascular fraction (SVF) plated on SB or SBlyo. After 14 days, significant cell proliferation improvement was observed on SBlyo with respect to SB, where cells filled the cavities between the native trabeculae. On SB, on the other hand, the process was still present, but tissue formation was less organized at 60 days. On both scaffolds, cells differentiated into osteoblasts and were able to mineralize after 60 days. Nonetheless, SBlyo showed a higher expression of osteoblast markers and a higher quantity of newly formed trabeculae than SB alone. The quantification analysis of the newly formed mineralized tissue and the immunohistochemical studies demonstrated that SBlyo induces bone formation more effectively. This osteoinductive effect is likely due to the osteogenic factors present in the lyosecretome, such as fibronectin, alpha-2-macroglobulin, apolipoprotein A, and TGF-β. |
| first_indexed | 2024-03-10T12:19:19Z |
| format | Article |
| id | doaj.art-35281662949249848dc08dcb588b8908 |
| institution | Directory Open Access Journal |
| issn | 1661-6596 1422-0067 |
| language | English |
| last_indexed | 2024-03-10T12:19:19Z |
| publishDate | 2021-04-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | International Journal of Molecular Sciences |
| spelling | doaj.art-35281662949249848dc08dcb588b89082023-11-21T15:37:24ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672021-04-01228406410.3390/ijms22084064Biohybrid Bovine Bone Matrix for Controlled Release of Mesenchymal Stem/Stromal Cell Lyosecretome: A Device for Bone RegenerationElia Bari0Ilaria Roato1Giuseppe Perale2Filippo Rossi3Tullio Genova4Federico Mussano5Riccardo Ferracini6Marzio Sorlini7Maria Luisa Torre8Sara Perteghella9Department of Drug Sciences, University of Pavia, Viale Taramelli 12, I-27100 Pavia, ItalyDepartment of Surgical Sciences, CIR-Dental School, University of Torino, Via Nizza 230, I-10126 Torino, ItalyIndustrie Biomediche Insubri SA, Via Cantonale 67, CH-6805 Mezzovico-Vira, SwitzerlandDepartment of Chemistry, Materials and Chemical Engineering “Giulio Natta”, Politecnico di Milano, Via Mancinelli 7, I-20131 Milano, ItalyDepartment of Life Sciences and Systems Biology, University of Torino, Via Accademia Albertina 13, I-10123 Torino, ItalyDepartment of Surgical Sciences, CIR-Dental School, University of Torino, Via Nizza 230, I-10126 Torino, ItalyDepartment of Surgical Sciences and Integrated Diagnostics, University of Genova, Viale Benedetto XV 6, I-16132 Genova, ItalySUPSI—Department of Innovative Technologies, Lugano University Centre, Campus Est, Via la Santa 1, CH-6962 Viganello, SwitzerlandDepartment of Drug Sciences, University of Pavia, Viale Taramelli 12, I-27100 Pavia, ItalyDepartment of Drug Sciences, University of Pavia, Viale Taramelli 12, I-27100 Pavia, ItalySmartBone<sup>®</sup> (SB) is a biohybrid bone substitute advantageously proposed as a class III medical device for bone regeneration in reconstructive surgeries (oral, maxillofacial, orthopedic, and oncology). In the present study, a new strategy to improve SB osteoinductivity was developed. SB scaffolds were loaded with lyosecretome, a freeze-dried formulation of mesenchymal stem cell (MSC)-secretome, containing proteins and extracellular vesicles (EVs). Lyosecretome-loaded SB scaffolds (SBlyo) were prepared using an absorption method. A burst release of proteins and EVs (38% and 50% after 30 min, respectively) was observed, and then proteins were released more slowly with respect to EVs, most likely because they more strongly adsorbed onto the SB surface. In vitro tests were conducted using adipose tissue-derived stromal vascular fraction (SVF) plated on SB or SBlyo. After 14 days, significant cell proliferation improvement was observed on SBlyo with respect to SB, where cells filled the cavities between the native trabeculae. On SB, on the other hand, the process was still present, but tissue formation was less organized at 60 days. On both scaffolds, cells differentiated into osteoblasts and were able to mineralize after 60 days. Nonetheless, SBlyo showed a higher expression of osteoblast markers and a higher quantity of newly formed trabeculae than SB alone. The quantification analysis of the newly formed mineralized tissue and the immunohistochemical studies demonstrated that SBlyo induces bone formation more effectively. This osteoinductive effect is likely due to the osteogenic factors present in the lyosecretome, such as fibronectin, alpha-2-macroglobulin, apolipoprotein A, and TGF-β.https://www.mdpi.com/1422-0067/22/8/4064bone graftingmesenchymal stem cellsMSC-secretomeMSC-extracellular vesiclesMSC-exosomesbone regeneration |
| spellingShingle | Elia Bari Ilaria Roato Giuseppe Perale Filippo Rossi Tullio Genova Federico Mussano Riccardo Ferracini Marzio Sorlini Maria Luisa Torre Sara Perteghella Biohybrid Bovine Bone Matrix for Controlled Release of Mesenchymal Stem/Stromal Cell Lyosecretome: A Device for Bone Regeneration International Journal of Molecular Sciences bone grafting mesenchymal stem cells MSC-secretome MSC-extracellular vesicles MSC-exosomes bone regeneration |
| title | Biohybrid Bovine Bone Matrix for Controlled Release of Mesenchymal Stem/Stromal Cell Lyosecretome: A Device for Bone Regeneration |
| title_full | Biohybrid Bovine Bone Matrix for Controlled Release of Mesenchymal Stem/Stromal Cell Lyosecretome: A Device for Bone Regeneration |
| title_fullStr | Biohybrid Bovine Bone Matrix for Controlled Release of Mesenchymal Stem/Stromal Cell Lyosecretome: A Device for Bone Regeneration |
| title_full_unstemmed | Biohybrid Bovine Bone Matrix for Controlled Release of Mesenchymal Stem/Stromal Cell Lyosecretome: A Device for Bone Regeneration |
| title_short | Biohybrid Bovine Bone Matrix for Controlled Release of Mesenchymal Stem/Stromal Cell Lyosecretome: A Device for Bone Regeneration |
| title_sort | biohybrid bovine bone matrix for controlled release of mesenchymal stem stromal cell lyosecretome a device for bone regeneration |
| topic | bone grafting mesenchymal stem cells MSC-secretome MSC-extracellular vesicles MSC-exosomes bone regeneration |
| url | https://www.mdpi.com/1422-0067/22/8/4064 |
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