Chitosan Nanoparticles, Gene Delivery, Mesenchymal Stem Cells (MSCs), Gene-Activated Scaffold, Tissue Engineering
This work was funded by Science Foundation Ireland (SFI) Research Frontiers Programme (Grant No. 11/RFP/ENM/3053), Collagen materials were provided by Integra Life Sciences, Inc. through a Material Transfer Agreement. We also thank Dr. M. Sawkins and the Centre for Research on Adaptive Nanostructures and Nanodevices (CRANN), Trinity College Dublin, for help with SEM and AFM imaging.
Biomaterial scaffolds that support cell infiltration and tissue formation can also function as platforms for the delivery of therapeutics such as drugs, proteins, and genes. As burst release of supraphysiological quantities of recombinant proteins can result in adverse side effects, the objective of this study was to explore the potential of a series of collagen-based scaffolds, developed in our laboratory, as gene-activated scaffold platforms with potential in a range of tissue engineering applications. The potential of chitosan, a biocompatible material derived from the shells of crustaceans, as a gene delivery vector was assessed using mesenchymal stem cells (MSCs). A transfection efficiency of >45% is reported which is similar to what is achieved with polyethyleneimine (PEI), a non-viral gold standard vector, without causing cytotoxic side effects. When the optimised chitosan nanoparticles were incorporated into a series of collagen-based scaffolds, sustained transgene expression from MSCs seeded on the scaffolds was maintained for up to 28days and interestingly the composition of the scaffold had an effect on transfection efficiency. These results demonstrate that by simply varying the scaffold composition and the gene (or combinations thereof) chosen; the system has potential for a myriad of therapeutic applications.
Rafferty RM, Tierney EG, Curtin CM, Cryan SA, O'Brien FJ. Development of a gene-activated scaffold platform for tissue engineering applications using chitosan-pDNA nanoparticles on collagen-based scaffolds. Journal of Control Release. 2015;210:84-94.
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