Simultaneous Delivery of Highly Diverse Bioactive Compounds from Blend Electrospun Fibers for Skin Wound Healing

Abstract

Blend emulsion electrospinning is widely perceived to destroy the bioactivity of proteins, and a blend emulsion of water-soluble and nonsoluble molecules is believed to be thermodynamically unstable to electrospin smoothly. Here we demonstrate a method to retain the bioactivity of disparate fragile biomolecules when electrospun. Using bovine serum albumin as a carrier protein; water-soluble vitamin C, fat soluble vitamin D3, steroid hormone hydrocortisone, peptide hormone insulin, thyroid hormone triiodothyronine (T3), and peptide epidermal growth factor (EGF) were simultaneously blend-spun into PLGA-collagen nanofibers. Upon release, vitamin C maintained the ability to facilitate Type I collagen secretion by fibroblasts, EGF stimulated skin fibroblast proliferation, and insulin potentiated adipogenic differentiation. Transgenic cell reporter assays confirmed the bioactivity of vitamin D3, T3, and hydrocortisone. These factors concertedly increased keratinocyte and fibroblast proliferation while maintaining keratinocyte basal state. This method presents an elegant solution to simultaneously deliver disparate bioactive biomolecules for wound healing applications.

Protein-loaded emulsion electrospun fibers optimized for bioactivity retention and pH-controlled release for peroral delivery of biologic therapeutics

“…Their study used similar emulsion electrospinning parameters as in our study (10% aqueous phase, non-ionic surfactant), and the lack of bioactive protein detected from their emulsion electrospun fibers may be due to the differences in polymers and organic solvents used or the inherent instability of growth factor proteins, which have half-lives on the order of minutes (Tessmar and Göpferich, 2007). A study by Peh et al loaded multiple proteins into poly(lactic-co-glycolic acid) emulsion electrospun fibers with a 10% aqueous phase and found that the bioactivity recovered was highly dependent on the protein (Peh et al, 2015), as is supported by the results of our study. Finally, many studies incorporating proteins into electrospun fibers for wound healing and tissue engineering demonstrate function of the encapsulated proteins but bioactivity retention is not quantified due to the non-enzymatic nature of the protein investigated (Briggs et al, 2015; Choi et al, 2015; Hu et al, 2016; Li et al, 2010; Wang et al, 2015).…”

Protein nanocoatings on synthetic polymeric nanofibrous membranes designed as carriers for skin cells

“…11 In skin substitutes, collagen is often applied in the form of a gel, 12,13 or it is used in composites with other natural or synthetic materials. 14,15 Previous studies have revealed that collagen supports wound healing. Niiyama and Kuroyanagi combined collagen with hyaluronic acid and functionalized this composite with EGF.…”

Nanoparticles and nanofibers for topical drug delivery

“…Recently, Peh et al impregnated a cocktail of compounds (Vitamin C, hydrocortisone, insulin, triiodothyronine, EGF, and Vitamin D3) into electrospun PLGA/collagen fiber mats and tested their potential utility in wound healing applications. These researchers also confirmed the bioactivity of the released molecules in vitro [171]. …”