Controlled release of strontium through neutralization reaction within a methoxy(Polyethylene glycol)-polyester hydrogel

Background: The aim of this study was to develop a minimally invasive hydrogel system that can release strontium ions, an element that has been shown to increase osteoblast proliferation and prohibit bone resorption, in a controlled manner. Methods: SrCO₃ was selected as the salt of choice due to potential acid neutralization reaction between SrCO₃ and degradation by-products of methoxy(polyethylene glycol)-co-poly(lactic-co-glycolic acid) (mPEG-PLGA): namely, lactic acid and glycolic acid. SrCO₃ was incorporated into mPEG-PLGA hydrogel, and the system was assessed for gelation properties, drug release and biocompatibility. Results: SrCO₃ incorporation at hydrogel to SrCO₃ ratios of 5:1, 3:1 and 1:1 (wt%) did not compromise the thermosensitivity of mPEG-PLGA hydrogels. Furthermore, incorporation of SrCO₃ at 1:1 ratio prevented copolymer self-catalysis and decreased hydrogel weight loss from 85% to 61% in vitro after 30 days. During the 30-day time frame, zero-order strontium release was observed and was correlated to hydrogel degradation and acidity. The addition of SrCO₃ also improved in vivo hydrogel biocompatibility, due to moderation of acidic microenvironment and amelioration of inflammatory response. Conclusions: These results showed that the described system is suitable for the extended release of strontium and exhibits potential for localized treatment for osteoporosis or as a bone void filler.