title: pGlcNAc Nanofiber Treatment of Cutaneous Wounds Stimulate Increased Tensile Strength and Reduced Scarring via Activation of Akt1.
abstract: Treatment of cutaneous wounds with poly-N-acetyl-glucosamine containing nanofibers (pGlcNAc), a novel polysaccharide material derived from a marine diatom, results in increased wound closure, antibacterial activities and innate immune responses. We have shown that Akt1 plays a central role in the regulation of these activities. Here, we show that pGlcNAc treatment of cutaneous wounds results in a smaller scar that has increased tensile strength and elasticity. pGlcNAc treated wounds exhibit decreased collagen content, increased collagen organization and decreased myofibroblast content. A fibrin gel assay was used to assess the regulation of fibroblast alignment in vitro. In this assay, fibrin lattice is formed with two pins that provide focal points upon which the gel can exert force as the cells align from pole to pole. pGlcNAc stimulation of embedded fibroblasts results in cellular alignment as compared to untreated controls, by a process that is Akt1 dependent. We show that Akt1 is required in vivo for the pGlcNAc-induced increased tensile strength and elasticity. Taken together, our findings suggest that pGlcNAc nanofibers stimulate an Akt1 dependent pathway that results in the proper alignment of fibroblasts, decreased scarring, and increased tensile strength during cutaneous wound healing.
authors.affiliation: Department Regenerative Medicine and Cell Biology, Medical University of South Carolina, Charleston, SC, 29425, United States of America.
authors.forename: Haley Buff
authors.initials: HB
authors.lastname: Lindner
authors.affiliation: Department Regenerative Medicine and Cell Biology, Medical University of South Carolina, Charleston, SC, 29425, United States of America.
authors.forename: Lloyd McPherson
authors.initials: LM
authors.lastname: Felmly
authors.affiliation: Marine Polymer Technologies, Inc., Danvers, MA, 01923, United States of America.
authors.forename: Marina
authors.initials: M
authors.lastname: Demcheva
authors.affiliation: Sunnybrook Research Institute, University of Toronto, Toronto, Ontario, M5G 1G6, Canada.
authors.forename: Arun
authors.initials: A
authors.lastname: Seth
authors.affiliation: Department Regenerative Medicine and Cell Biology, Medical University of South Carolina, Charleston, SC, 29425, United States of America.
authors.forename: Russell
authors.initials: R
authors.lastname: Norris
authors.affiliation: Department of Medicine, Medical University of South Carolina, Charleston, SC, 29425, United States of America.
authors.forename: Amy D
authors.initials: AD
authors.lastname: Bradshaw
authors.affiliation: Marine Polymer Technologies, Inc., Danvers, MA, 01923, United States of America.
authors.forename: John
authors.initials: J
authors.lastname: Vournakis
authors.affiliation: Department Regenerative Medicine and Cell Biology, Medical University of South Carolina, Charleston, SC, 29425, United States of America.
authors.forename: Robin C
authors.initials: RC
authors.lastname: Muise-Helmericks
mesh_terms: D000117:Acetylglucosamine / Q000008:administration & dosage* / Q000737:chemistry / Q000494:pharmacology; D000818:Animals; D000900:Anti-Bacterial Agents / Q000008:administration & dosage / Q000494:pharmacology; D002921:Cicatrix / Q000188:drug therapy*; D005786:Gene Expression Regulation / Q000187:drug effects; D051379:Mice; D057139:Nanofibers / Q000737:chemistry; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects; D012867:Skin / Q000187:drug effects / Q000293:injuries*; D013718:Tensile Strength / Q000187:drug effects*; D014945:Wound Healing
chemical_list: D000900:Anti-Bacterial Agents; C113831:poly-N-acetyl glucosamine; C514862:Akt1 protein, mouse; D051057:Proto-Oncogene Proteins c-akt; D000117:Acetylglucosamine