Abstract
Strontium- and calcium-releasing, titanium-stabilised phosphate-based glasses with a controlled degradation rate are currently under development for orthopaedic tissue engineering applications. Ca and/or Sr were incorporated at varying concentrations in quaternary phosphate-based glasses, in order to promote osteoinduction. Ti was incorporated at a fixed concentration in order to prolong degradation. Glasses of the general formula (P2O5)–(Na2O)–(TiO2)–(CaO)–(SrO) were prepared via the melt-quench technique. The materials were characterised by energy-dispersive X-ray spectroscopy, X-ray diffraction, 31P magic angle spinning nuclear magnetic resonance, Fourier transform infrared spectroscopy, differential thermal analysis and density determination. The dissolution rate in distilled water was determined by measuring mass loss, ion release and pH change over a two-week period. In addition, the cytocompatibility and alkaline phosphatase activity of an osteoblast-like cell line cultured on the surface of glass discs was assessed. The glasses were shown to be amorphous and contained Q1, Q2 and Q3 species. Fourier transform infrared spectroscopy revealed small changes in the glass structure as Ca was substituted with Sr and differential thermal analysis confirmed a decrease in crystallisation temperature with increasing Sr content. Degradation and ion release studies also showed that mass loss was positively correlated with Sr content. These results were attributed to the lower electronegativity of Sr in comparison to Ca favouring the formation of phosphate-based mineral phases. All compositions supported cell proliferation and survival and induced at least 2.3-fold alkaline phosphatase activity relative to the control. Glass containing 17.5 mol% Sr had 3.6-fold greater alkaline phosphatase activity than the control. The gradual release of Ca and Sr supported osteoinduction, indicating their potential suitability in orthopaedic tissue engineering applications.
Highlights
Osteoporosis is a progressive bone disease, most common in post-menopausal women, in which the delicate balance of bone turnover is disrupted
While silica-based glasses typically take several years to dissolve,[5] the dissolution rate of phosphate-based glasses can be varied over several orders of magnitude, from $2 h to >1 year, via the addition of oxide modifiers, such as TiO2, which increase the stability of network crosslinks.[6]
The following chemical precursors were used without further purification: diphosphorus pentoxide (P2O5, 98%, VWR, Lutterworth, UK), sodium dihydrogen phosphate (NaH2PO4, 99%, VWR), titanium oxide (TiO2, 99%, VWR), calcium carbonate (CaCO3, 98.5%, VWR) and strontium carbonate (SrCO3, 98.5%, BDH Laboratory Supplies, Poole, UK)
Summary
Osteoporosis is a progressive bone disease, most common in post-menopausal women, in which the delicate balance of bone turnover is disrupted. A wide range of orthopaedic materials have been developed over the past 50 years for the treatment of fractures caused by osteoporosis, congenital disorders such as osteogenesis imperfecta and cleft palate, or injury One such class of materials is phosphate-based glasses, which are advantageous over silica-based glasses due to their more controllable dissolution rate.[2,4] While silica-based glasses typically take several years to dissolve,[5] the dissolution rate of phosphate-based glasses can be varied over several orders of magnitude, from $2 h to >1 year, via the addition of oxide modifiers, such as TiO2, which increase the stability of network crosslinks.[6] This in turn enables precise tuning of the degradation rate for controlled release of ions that promote or inhibit specific cellular process,[7] e.g. induction of bone formation (Ca2þ, Sr2þ, polyphosphates)[6,8,9]; promotion of vascularisation and angiogenesis (Co2þ and Cu2þ)[10,11] and antimicrobial action (Agþ, Cu2þ, FÀ, Zn2þ).[12,13] the tuneable degradation rate of phosphate-based glasses can be targeted to match that of tissue turnover, e.g. bone resorption and deposition, for promotion of osseointegration. Combined with their similar composition to the mineral phase of bone, this makes phosphate-based glasses suitable for various orthopaedic tissue engineering applications, including coatings for dental, maxillofacial and orthopaedic implants and scaffolds for bone tissue engineering
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