In vitro cellular testing of strontium/calcium substituted phosphate glass discs and microspheres shows potential for bone regeneration

Patel, U. and Macri-Pellizzeri, L. and Zakir Hossain, K.M. and Scammell, B.E. and Grant, D.M. and Scotchford, C.A. and Hannon, A.C. and Kennedy, A.R. and Barney, E.R. and Ahmed, I. and Sottile, V. (2019) In vitro cellular testing of strontium/calcium substituted phosphate glass discs and microspheres shows potential for bone regeneration. Journal of Tissue Engineering and Regenerative Medicine, 13 (3). pp. 396-405. ISSN 1932-6254

Abstract

Phosphate-based glasses (PBGs) are ideal materials for regenerative medicine strategies because their composition, degradation rates, and ion release profiles can easily be controlled. Strontium has previously been found to simultaneously affect bone resorption and deposition. Therefore, by combining the inherent properties of resorbable PBG and therapeutic activity of strontium, these glasses could be used as a delivery device of therapeutic factors for the treatment of orthopaedic diseases such as osteoporosis. This study shows the cytocompatibility and osteogenic potential of PBGs where CaO is gradually replaced by SrO in the near invert glass system 40P 2 O 5 ·(16-x)CaO·20Na 2 O·24MgO·xSrO (x = 0, 4, 8, 12, and 16 mol%). Direct seeding of MG63 cells onto glass discs showed no significant difference in cell metabolic activity and DNA amount measurement across the different formulations studied. Cell attachment and spreading was confirmed via scanning electron microscopy (SEM) imaging at Days 3 and 14. Alkaline phosphatase (ALP) activity was similarly maintained across the glass compositions. Follow-on studies explored the effect of each glass composition in microsphere conformation (size: 63-125 μm) on human mesenchymal stem cells (hMSCs) in 3D cultures, and analysis of cell metabolic activity and ALP activity showed no significant differences at Day 14 over the compositional range investigated, in line with the observations from MG63 cell culture studies. Environmental SEM and live cell imaging at Day 14 of hMSCs seeded on the microspheres showed cell attachment and colonisation of the microsphere surfaces, confirming these formulations as promising candidates for regenerative medicine strategies addressing compromised musculoskeletal/orthopaedic diseases.