Journal article
Nonviral Gene Delivery Embedded in Biomimetically Mineralized Matrices for Bone Tissue Engineering
Tissue engineering. Part A, Vol.27(15-16), pp.174-1083
11/26/2020
DOI: 10.1089/ten.tea.2020.0206
PMCID: PMC8420947
PMID: 33086991
Abstract
Research in bone tissue engineering aims to design materials that are effective at generating bone without causing significant side effects. The osteogenic potential of combining matrices and protein growth factors has been well documented, however, improvements are necessary to achieve optimal therapeutic benefits upon clinical translation. In this article, rat calvarial defects were treated with gene-activated matrices (GAMs). The GAMs used were collagen sponges mineralized with a simulated body fluid (SBF) containing a nonviral gene delivery system. Both
and
studies were performed to determine the optimal mode of gene delivery. After 6 weeks, the defects were extracted to assess bone formation and tissue quality through histological and microcomputed tomography analyses. The optimal GAM consisted of a collagen sponge with polyethylenimine plasmid DNA (PEI-pDNA) complexes embedded in a calcium phosphate coating produced by SBF, which increased total bone formation by 39% compared with 19% for control samples. A follow-up
study was performed to optimize the ratio of growth factors included in the GAM. The optimal ratio for supporting bone formation after 6 weeks of implantation was five parts of pBMP-2 to three parts pFGF-2. These studies demonstrated that collagen matrices biomimetically mineralized and activated with plasmids encoding fibroblast growth factor-2 (FGF-2) and bone morphogenetic protein-2 (BMP-2) can optimally improve bone regeneration outcomes. Impact statement Bone tissue engineering has explored both nonviral gene delivery and the concept of biomimetic mineralization. In this study, we combined these two concepts to further enhance bone regeneration outcomes. We demonstrated that embedding polyethylenimine (PEI)-based gene delivery within a mineral layer formed from simulated body fluid (SBF) immersion can increase bone formation rates. We also demonstrated that the ratio of growth factors utilized for matrix fabrication can impact the amount of bone formed in the defect site. This research highlights a combined approach using SBF and nonviral gene delivery both
and
and prepares the way for future optimization of synthetic gene activated matrices.
Details
- Title: Subtitle
- Nonviral Gene Delivery Embedded in Biomimetically Mineralized Matrices for Bone Tissue Engineering
- Creators
- Timothy M Acri - University of IowaNoah Z Laird - University of IowaLeela R Jaidev - University of IowaDavid K Meyerholz - University of IowaAliasger K Salem - University of IowaKyungsup Shin - University of Iowa
- Resource Type
- Journal article
- Publication Details
- Tissue engineering. Part A, Vol.27(15-16), pp.174-1083
- DOI
- 10.1089/ten.tea.2020.0206
- PMID
- 33086991
- PMCID
- PMC8420947
- NLM abbreviation
- Tissue Eng Part A
- ISSN
- 1937-3341
- eISSN
- 1937-335X
- Grant note
- P30 ES005605 / NIEHS NIH HHS
- Language
- English
- Date published
- 11/26/2020
- Academic Unit
- Roy J. Carver Department of Biomedical Engineering; Orthodontics; Pathology; Pharmaceutical Sciences and Experimental Therapeutics; Craniofacial Anomalies Research Center; Dental Research; Chemical and Biochemical Engineering
- Record Identifier
- 9984186678802771
Metrics
4 Record Views