A particle-filled hydrogel based on alginate and calcium phosphate nanoparticles as bone adhesive.

The clinical need for bone adhesives as an alternative to osteosynthesis is evident. However, this is a challenging problem due to the moist environment in surgical sites with bone surfaces covered with blood and biomolecules like lipids or proteins. A nanoparticle-loaded hydrogel that is based on a freeze-dried powder of silica-coated calcium phosphate/carboxymethyl cellulose nanoparticles (CaP/CMC/SiO2) and an aqueous solution of sodium alginate (2 wt%) was developed and optimized with respect to the gluing ability in air and in water. The final paste was crosslinked within about one minute by calcium ions released from the calcium phosphate nanoparticles and contained about 20 wt% nanoparticles and 80 wt% water. The mechanical properties of the hydrogel were determined by extensive rheological tests. The thixotropic pasty hydrogel can be applied with a syringe. The adhesion strength was about 84 kPa between moist bone fragments in air. The hydrogel kept fragments of cortical bone well connected for >3 months during complete submersion in water. Besides water, the material consists only of biocompatible and biodegradable components (calcium phosphate, CMC, alginate). It carries only a very low dose of these materials into the bone site (mainly calcium phosphate nanoparticles). In-vitro cell culture with hMSCs that differentiated to osteoblasts confirmed a good biocompatibility of the bone adhesive formulation.