Journal
JOURNAL OF BIOMEDICAL MATERIALS RESEARCH PART A
Volume 92A, Issue 3, Pages 1131-1138Publisher
WILEY
DOI: 10.1002/jbm.a.32441
Keywords
tissue engineering; bone; osteoblast; gene therapy; hydrogel
Funding
- Case Western Reserve University
- Ellison Medical Foundation (EA)
- National Science Foundation Graduate Research Fellowship (MDK)
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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 run, 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 the backs of mice. This and injected subcutaneously in injectable, minimally invasive gene delivery system may be efficacious in bone regeneration applications. (D 2009 Wiley Periodicals, Inc. J Biomed Mater Res 92A: 1131-1138, 2010
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