Localized temporal co-delivery of interleukin 10 and decorin genes using amediated by collagen-based biphasic scaffold modulates the expression of TGF-β1/β2 in a rabbit ear hypertrophic scarring model
Ciarstan McArdle, Sunny Akogwu Abbah, Sirsendu Bhowmick, Estelle Collin, Abhay Pandit
Abstract
Hypertrophic scarring (HS) is an intractable complication associated with cutaneous wound healing. Although transforming growth factor β1 (TGF-β1) has long been documented as a central regulatory cytokine in fibrogenesis and fibroplasia, there is currently no cure. Gene therapy is emerging as a powerful tool to attenuate the overexpression of TGF-β1 and its signaling activities. An effective approach may require transferring multiple genes to regulate different aspects of TGF-β1 signaling activities in a Spatio-temporal manner. Herein we report the additive anti-fibrotic effects of two plasmid DNAs encoding interleukin 10 (IL-10) and decorin (DCN) co-delivered via a biphasic 3D collagen scaffold reservoir platform. Combined gene therapy significantly attenuated inflammation and extracellular matrix components' accumulation in a rabbit ear ulcer model; and suppressed the expressions of genes associated with fibrogenesis, including collagen type I, as well as TGF-β1 and TGF-β2, while enhancing the genes commonly associated with regenerative healing including collagen type III. These findings may serve to provide a non-viral gene therapy platform that is safe, optimized, and effective to deliver multiple genes onto the diseased tissue in a wider range of tissue fibrosis-related maladies.