Journal article
Chemically modified RNA activated matrices enhance bone regeneration
Journal of controlled release, Vol.218, pp.22-28
11/28/2015
DOI: 10.1016/j.jconrel.2015.09.050
PMCID: PMC4631704
PMID: 26415855
Abstract
There exists a dire need for improved therapeutics to achieve predictable bone regeneration. Gene therapy using non-viral vectors that are safe and efficient at transfecting target cells is a promising approach to overcoming the drawbacks of protein delivery of growth factors. Here, we investigated the transfection efficiency, cytotoxicity, osteogenic potential and in vivo bone regenerative capacity of chemically modified ribonucleic acid (cmRNA) (encoding BMP-2) complexed with polyethylenimine (PEI) and made comparisons with PEI complexed with conventional plasmid DNA (encoding BMP-2). The polyplexes were fabricated at an amine (N) to phosphate (P) ratio of 10 and characterized for transfection efficiency using human bone marrow stromal cells (BMSCs). The osteogenic potential of BMSCs treated with these polyplexes was validated by determining the expression of bone-specific genes, osteocalcin and alkaline phosphatase as well as through the detection of bone matrix deposition. Using a calvarial bone defect model in rats, it was shown that PEI-cmRNA (encoding BMP-2)-activated matrices promoted significantly enhanced bone regeneration compared to PEI-plasmid DNA (BMP-2)-activated matrices. Our proof of concept study suggests that scaffolds loaded with non-viral vectors harboring cmRNA encoding osteogenic proteins may be a powerful tool for stimulating bone regeneration with significant potential for clinical translation. [Display omitted]
Details
- Title: Subtitle
- Chemically modified RNA activated matrices enhance bone regeneration
- Creators
- Satheesh Elangovan - Department of Periodontics, University of Iowa College of Dentistry, Iowa City, IA, United StatesBehnoush Khorsand - Division of Pharmaceutics and Translational Therapeutics, University of Iowa College of Pharmacy, Iowa City, IA, United StatesAnh-Vu Do - Division of Pharmaceutics and Translational Therapeutics, University of Iowa College of Pharmacy, Iowa City, IA, United StatesLiu Hong - Department of Prosthodontics, University of Iowa College of Dentistry, Iowa City, IA, United StatesAlexander Dewerth - Department of Pediatrics I–Pediatric Infectiology and Immunology, Translational Genomics and Gene Therapy, University of Tübingen, Wilhelstr. 56, 72074 Tübingen, GermanyMichael Kormann - Department of Pediatrics I–Pediatric Infectiology and Immunology, Translational Genomics and Gene Therapy, University of Tübingen, Wilhelstr. 56, 72074 Tübingen, GermanyRyan D Ross - Department of Anatomy and Cell Biology, Rush Medical College, Chicago, IL, United StatesD Rick Sumner - Department of Anatomy and Cell Biology, Rush Medical College, Chicago, IL, United StatesChantal Allamargot - Central Microscopy Research Facility, University of Iowa, Iowa City, IA, United StatesAliasger K Salem - Department of Periodontics, University of Iowa College of Dentistry, Iowa City, IA, United States
- Resource Type
- Journal article
- Publication Details
- Journal of controlled release, Vol.218, pp.22-28
- DOI
- 10.1016/j.jconrel.2015.09.050
- PMID
- 26415855
- PMCID
- PMC4631704
- NLM abbreviation
- J Control Release
- ISSN
- 0168-3659
- eISSN
- 1873-4995
- Publisher
- Elsevier B.V
- Grant note
- DOI: 10.13039/100000002, name: NIH, award: 1R21DE024206-01A1; name: University of Iowa Start-up Grant; name: ITI Foundation for the Promotion of Implantology, Switzerland, award: 855 2012; name: Osteology Foundation Grant, award: 12-054; name: Sunstar — American Academy of Periodontology Foundation Research Fellowship; DOI: 10.13039/501100001659, name: Deutsche Forschungsgemeinschaft; name: Lyle and Sharon Bighley Professorship
- Language
- English
- Date published
- 11/28/2015
- Academic Unit
- Roy J. Carver Department of Biomedical Engineering; Core Research Facilities; Pharmaceutical Sciences and Experimental Therapeutics; Prosthodontics; Craniofacial Anomalies Research Center; Dental Research; Chemical and Biochemical Engineering; Periodontics
- Record Identifier
- 9983985835202771
Metrics
41 Record Views