Calcium phosphate-DNA nanoparticle gene delivery from alginate hydrogels induces in vivo osteogenesis

Abstract

There is a significant need for improved therapy for bone regeneration. The delivery of recombinant bone morphogenetic proteins has been approved for clinical use to promote osteogenesis, but still has limitations such as expense, degradation of the proteins in vivo and difficulties retaining protein at the site of injury. Localized gene delivery is a promising alternative therapy, as it would allow sustained expression of specific osteoinductive growth factors by cells near the damaged site. We have engineered an injectable system for localized, sustained nonviral gene delivery from alginate hydrogels containing preosteoblastic cells and calcium phosphate-DNA nanoparticles. The nanoparticles utilized in this report are stable, on the order of 100 nm, and have a high DNA incorporation efficiency (>66%). When the nanoparticles were incorporated in alginate hydrogels, sustained release of DNA was observed. Furthermore, MC3T3-E1 preosteoblast cells exhibited the capacity to form bony tissue in as little as two and half weeks when mixed with DNA nanoparticles encoding for BMP-2 into the alginate hydrogels and injected subcutaneously in the backs of mice. This injectable, minimally invasive gene delivery system may be efficacious in bone regeneration applications.