Osteostatin potentiates the bioactivity of mesoporous glass scaffolds containing Zn2+ ions in human mesenchymal stem cells. (15th April 2019)

• Record Type: Journal Article
• Authors: Heras, C.; Sanchez-Salcedo, S.; Lozano, D.; Peña, J.; Esbrit, P.; Vallet-Regi, M.; Salinas, A.J.
• Is Part Of: Acta biomaterialia. Volume 89(2019)
• Page Start: 359
• Page End: 371
• Publication Date: 2019-04-15
• Subjects: Mesoporous bioactive glasses -- ZnO -- Osteostatin -- Human mesenchymal cells; Biomedical materials -- Periodicals; 610.28
• DOI: 10.1016/j.actbio.2019.03.033
• Languages: English
• ISSNs: 1742-7061

Abstract

Graphical abstract: Abstract: There is an urgent need of biosynthetic bone grafts with enhanced osteogenic capacity. In this study, we describe the design of hierarchical meso -macroporous 3D-scaffolds based on mesoporous bioactive glasses (MBGs), enriched with the peptide osteostatin and Zn 2+ ions, and their osteogenic effect on human mesenchymal stem cells (hMSCs) as a preclinical strategy in bone regeneration. The MBG compositions investigated were 80%SiO2 –15%CaO–5%P2 O5 (in mol-%) Blank (BL), and two analogous glasses containing 4% ZnO (4ZN) and 5% ZnO (5ZN). By using additive fabrication techniques, scaffolds exhibiting hierarchical porosity: mesopores (around 4 nm), macropores (1–600 μm) and big channels (∼1000 μm), were prepared. These MBG scaffolds with or without osteostatin were evaluated in hMCSs cultures. Zinc promoted hMSCs colonization (both the surface and inside) of MBG scaffolds. Moreover, Zn 2+ ions and osteostatin together, but not independently, in the scaffolds were found to induce the osteoblast differentiation genes runt related transcription factor-2 (RUNX2) and alkaline phosphatase (ALP) in hMSCs after 7 d of culture in the absence of an osteogenic differentiation-promoting medium. These results add credence to the combined use of zinc and osteostatin as an effective strategy for bone regeneration applications. Statement of significance: Mesoporous bioactive glasses (MBGs) are bioceramics whose unique properties make them excellent materials for bone tissue engineering. Physico-chemical characterization of MBGs as scaffolds made by rapid prototyping, doped with zinc (potential osteogenic, angiogenic and bactericidal ion) and loaded with osteostatin (osteogenic peptide) are described. These Zn-MBGs scaffolds showed 3D hierarchical meso -macroporous structure that enables to host and release osteostatin. When decorated with human mesenchymal stem cells (hMSCs), MBGs scaffolds enriched with both zinc and osteostatin exhibited a synergistic effect to enhance hMSCs growth, and also hMSCs osteogenic differentiation without addition of other osteoblastic differentiation factors to the culture medium. This novel strategy has a great potential for use in bone tissue engineering.