Timothy M. Acri (1), Noah Z. Laird (1), LR Jaidev (1), David K. Meyerholz (2), Aliasger K. Salem (1),Kyungsup Shin (3)
Tissue Engineering Part A, 27, Issue 15-16, August 2021: 1074-1083. DOI: 10.1089/ten.tea.2020.0206

Keywords

gene therapy; tissue engineering; polyethylenimine; simulated body fluid; calvarial defect model

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 in vitro and in vivo 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 in vivo 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.

How Our Software Was Used

Dragonfly was used to calculate bone volume per total volume in X-ray bone scans.

Author Affiliation

(1) Department of Pharmaceutical Sciences and Experimental Therapeutics, University of Iowa College of Pharmacy, Iowa City, IA, United States.
(2) Department of Pathology, University of Iowa Carver College of Medicine, Iowa City, IA, United States.
(3) Department of Orthodontics, University of Iowa College of Dentistry and Dental Clinics, Iowa City, IA, United States.