Lindner Haley Buff, Felmly Lloyd McPherson, Demcheva Marina, Seth Arun, Norris Russell, Bradshaw Amy D, Vournakis John, Muise-Helmericks Robin C
Department Regenerative Medicine and Cell Biology, Medical University of South Carolina, Charleston, SC, 29425, United States of America.
Marine Polymer Technologies, Inc., Danvers, MA, 01923, United States of America.
PLoS One. 2015 May 8;10(5):e0127876. doi: 10.1371/journal.pone.0127876. eCollection 2015.
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.
用含聚-N-乙酰葡糖胺(pGlcNAc)的纳米纤维治疗皮肤伤口,pGlcNAc是一种源自海洋硅藻的新型多糖材料,可促进伤口愈合、增强抗菌活性并激发先天免疫反应。我们已经表明,Akt1在调节这些活性中起核心作用。在此,我们表明,用pGlcNAc治疗皮肤伤口会形成更小的疤痕,其拉伸强度和弹性增加。经pGlcNAc处理的伤口胶原蛋白含量降低,胶原蛋白排列增加,肌成纤维细胞含量减少。使用纤维蛋白凝胶试验评估体外成纤维细胞排列的调节。在该试验中,纤维蛋白晶格由两个销钉形成,当细胞从一极排列到另一极时,销钉提供凝胶可施加力的焦点。与未处理的对照相比,pGlcNAc刺激包埋的成纤维细胞导致细胞排列,这一过程依赖于Akt1。我们表明,在体内,Akt1是pGlcNAc诱导的拉伸强度和弹性增加所必需的。综上所述,我们的研究结果表明,pGlcNAc纳米纤维刺激了一条依赖于Akt1的途径,该途径导致成纤维细胞正确排列、疤痕形成减少以及皮肤伤口愈合过程中拉伸强度增加。