Osteoinductive chemically crosslinked hydrogel enables hydroxyapatite formation, enhanced by release of dexamethasone, strontium, and zinc, and exhibits antimicrobial properties

Abstract

Injectable hydrogels have the ability to bridge sites of bone fractures, favouring bone regeneration processes such as osteoinduction followed by osteoconduction, thereby restoring bone functions in terms of structural stability and support. The ideal material would also prevent the development of infections. Osteoinductive, osteoconductive, and antimicrobial hydrogels have not been developed yet. A hydrogel was prepared using poly(ethylene glycol) methyl ether methacrylate and 2-(dimethylamino)ethyl methacrylate, with bis[2-(methacryloyloxy)ethyl] phosphate as a crosslinker; dexamethasone and Sr and Zn ions were also incorporated. Dexamethasone and Sr and Zn ions were added into the hydrogel to encourage both bone regeneration and provide an antibacterial component, given the osteogenic/antimicrobial properties of these chemicals. The hydrogels were formulated using a crosslinker to create a rigid hydrogel capable of supporting bone regeneration while releasing the incorporated chemicals. Hydrogel polymerisation was characterised by pH and temperature changes. Hydrogel elasticity, stiffness, and viscosity were tested using a frequency sweep. The release of Sr and Zn ions and dexamethasone from hydrogels with different levels of crosslinker was also measured. The presence of hydroxyapatite, its deposition by osteoblasts and their growth, and the presence of osteocalcin were determined. The antibacterial effects were tested using Staphylococcus epidermidis and methicillin-resistant Staphylococcus aureus (MRSA). The results indicate that hydrogel swelling and changes in pH, temperature, and storage/loss modulus were favourable for the functional hydrogel, which could be injected at the fracture site. Osteoblast growth and hydroxyapatite formation were favoured by lower crosslinker concentrations, possibly influenced by the diffusion of Sr and Zn ions and dexamethasone through the hydrogel, while general cell viability was favoured by higher crosslinker concentrations. A slight antibacterial effect was observed for Sr- and Zn-releasing hydrogels compared to the standard hydrogel. The prepared hydrogel shows suitability as a material to bridge fracture sites while supporting osteoinduction in the presence of hydroxyapatite and osteocalcin and has the ability to prevent fracture-associated infections.