Polymeric Nanofibre Scaffold for the Delivery of a Transforming Growth Factor β1 Inhibitor

Abstract

Skin scarring is a highly prevalent and inevitable outcome of adult mammalian wound healing. Scar tissue is both pathologically and aesthetically inferior to the normal skin owing to elevated concentration of highly orientated collagen I architecture in the innate repaired tissue. With highly invasive surgery being the main treatment modality, there is a great need for alternative strategies to mitigate the problem of scar formation. Tissue engineering approaches using polymeric scaffolds have shown tremendous promise in various disease models including skin wound healing; however, the problem of skin scarring has been greatly overlooked. Herein, we developed an electrospun poly(glycidyl methacrylate) (ES-PGMA) scaffold incorporating a small-molecule antiscarring agent, PXS64. PXS64, a lipophilic neutral analogue of mannose-6-phosphate, has been shown to inhibit the activation of transforming growth factor β1 (TGFβ1). TGFβ1 is a primary protein cytokine regulating the expression of collagen I during wound healing and therefore governs the formation of scar tissue. The nanofibres were tested for biocompatibility as a tissue engineering scaffold and for their efficacy to inhibit TGFβ1 activation in human dermal skin fibroblasts.