Non-viral gene delivery embedded in biomimetically mineralized matrices for bone tissue engineering.

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 non-viral 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 micro-CT analyses. The optimal GAM consisted of a collagen scaffold with PEI-pDNA complexes embedded in a calcium phosphate coating produced by SBF, which increased total bone formation by 39% compared to 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 5 parts of pBMP-2 to 3 parts pFGF-2. These studies demonstrated that collagen matrices biomimetically mineralized and activated with plasmids encoding FGF-2 and BMP-2 can optimally improve bone regeneration outcomes.