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 40P2O5·(16‐x)CaO·20Na2O·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.
Highlights
Phosphate‐based glasses (PBGs) are highly suited biomaterials to deliver therapeutic ions, for bone regeneration, because their main constituents are found to occur in the inorganic phase of natural bone (Jones & Clare, 2012)
The results showed a significant increase in cell response over time (p < 0.0001), whereas no differences between cell cultures on the different PBG compositions were detected at each time point (p > 0.90; see Figure 2)
MG63 cells cultured on discs showed no significant difference in Alkaline phosphatase (ALP) activity across all the formulations tested in comparison with the Tissue culture plastic (TCP) control (p > 0.8; see Figure 3a)
Summary
Phosphate‐based glasses (PBGs) are highly suited biomaterials to deliver therapeutic ions, for bone regeneration, because their main constituents (i.e., calcium, phosphate, sodium, and magnesium) are found to occur in the inorganic phase of natural bone (Jones & Clare, 2012). The ability to control their dissolution rates, and the release of ions, serves as a highly attractive route to direct the biological response for the repair and regeneration of both hard and soft tissues (Hoppe, Guldal, & Boccaccini, 2011). Strontium ranelate was administrated to osteoporotic patients, due to its anabolic activity and antiresorptive effect on bone tissue (Ammann, 2005), as the imbalance of bone deposition and resorption characterises osteoporosis (Blake & Fogelman, 2006). Investigation into alternative administration routes such as controlled and localised delivery of the ion, as opposed to systemic delivery, could be very beneficial
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