2. Academic Validation
  3. Osteostatin potentiates the bioactivity of mesoporous glass scaffolds containing Zn2+ ions in human mesenchymal stem cells

Osteostatin potentiates the bioactivity of mesoporous glass scaffolds containing Zn2+ ions in human mesenchymal stem cells

  • Acta Biomater. 2019 Apr 15;89:359-371. doi: 10.1016/j.actbio.2019.03.033.
C Heras 1,  S Sanchez-Salcedo 2,  D Lozano 3,  J Peña 1,  P Esbrit 1,  M Vallet-Regi 3,  A J Salinas 4
Affiliations

Affiliations

  • 1 Departamento de Química en Ciencias Farmacéuticas, Facultad de Farmacia, Universidad Complutense de Madrid, UCM, Instituto de Investigación Hospital 12 de Octubre,i+12, 28040 Madrid, Spain.
  • 2 Departamento de Química en Ciencias Farmacéuticas, Facultad de Farmacia, Universidad Complutense de Madrid, UCM, Instituto de Investigación Hospital 12 de Octubre,i+12, 28040 Madrid, Spain; Networking Research Center on Bioengineering, Biomaterials and Nanomedicine (CIBER-BBN), Spain. Electronic address: [email protected].
  • 3 Departamento de Química en Ciencias Farmacéuticas, Facultad de Farmacia, Universidad Complutense de Madrid, UCM, Instituto de Investigación Hospital 12 de Octubre,i+12, 28040 Madrid, Spain; Networking Research Center on Bioengineering, Biomaterials and Nanomedicine (CIBER-BBN), Spain.
  • 4 Departamento de Química en Ciencias Farmacéuticas, Facultad de Farmacia, Universidad Complutense de Madrid, UCM, Instituto de Investigación Hospital 12 de Octubre,i+12, 28040 Madrid, Spain; Networking Research Center on Bioengineering, Biomaterials and Nanomedicine (CIBER-BBN), Spain. Electronic address: [email protected].
PMID: 30890462 DOI: 10.1016/j.actbio.2019.03.033
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 Zn2+ 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%P2O5 (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, Zn2+ 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 scaffoldsenriched with both zinc and osteostatin exhibited a synergistic effect to enhance hMSCs growth, and also hMSCs osteogenic differentiationwithout addition of other osteoblastic differentiation factors to the culture medium. This novel strategy has a great potential for use in bone tissue engineering.

Keywords

Human mesenchymal cells; Mesoporous bioactive glasses; Osteostatin; ZnO.

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