Grasman Jonathan M, Williams Marisa D, Razis Constantine G, Bonzanni Mattia, Golding Anne S, Cairns Dana M, Levin Michael, Kaplan David L
Department of Biomedical Engineering, Tufts University, Medford, Massachusetts 02155.
Allen Discovery Center, Tufts University, Medford, Massachusetts 02155.
ACS Biomater Sci Eng. 2019 Oct 14;5(10):5327-5336. doi: 10.1021/acsbiomaterials.9b00810. Epub 2019 Sep 18.
Scar formation is a natural result of almost all wound healing in adult mammals. Unfortunately, scarring disrupts normal tissue function and can cause significant physical and psychological distress. In addition to improving surgical techniques to limit scar formation, several therapies are under development towards the same goal. Many of these treatments aim to disrupt transforming growth factor β1 (TGFβ1) signaling, as this is a critical control point for fibroblast differentiation into myofibroblasts; a contractile cell that organizes synthesized collagen fibrils into scar tissue. The present study aimed to examine the role of hyperosmolar potassium gluconate (KGluc) on fibroblast function in skin repair. KGluc was first determined to negatively regulate fibroblast proliferation, metabolism, and migration in a dose-dependent manner . Increasing concentrations of KGluc also inhibited differentiation into myofibroblasts, suggesting that local KGluc treatment might reduce fibrosis. KGluc delivery was confirmed via loading into collagen hydrogels and used to treat a full thickness skin wound in mice. KGluc qualitatively slowed initial closure of the wounds and resulted in tissue that more closely resembled mature, healthy skin (epidermal thickness and dermal-epidermal morphology) when compared to unloaded collagen hydrogels. KGluc treatment significantly reduced the number of myofibroblasts within the dermis while upregulated blood vessel density with respect to unloaded hydrogels, likely a result of disruption of TGFβ1 signaling. Taken together, these data demonstrate the effectiveness of KGluc treatment on skin wound healing and suggest that this may be an efficient treatment to limit scar formation.
在成年哺乳动物中，瘢痕形成是几乎所有伤口愈合的自然结果。不幸的是，瘢痕会破坏正常组织功能，并可能导致严重的身体和心理困扰。除了改进手术技术以限制瘢痕形成外，还有几种疗法也在朝着同一目标进行研发。这些治疗方法中有许多旨在干扰转化生长因子β1（TGFβ1）信号传导，因为这是成纤维细胞分化为肌成纤维细胞的关键控制点；肌成纤维细胞是一种收缩细胞，可将合成的胶原纤维组织成瘢痕组织。本研究旨在探讨高渗葡萄糖酸钾（KGluc）在皮肤修复中对成纤维细胞功能的作用。首先确定KGluc以剂量依赖性方式负向调节成纤维细胞的增殖、代谢和迁移。KGluc浓度的增加也抑制了向肌成纤维细胞的分化，这表明局部KGluc治疗可能会减少纤维化。通过将KGluc加载到胶原水凝胶中来确认其递送，并用于治疗小鼠的全层皮肤伤口。与未加载的胶原水凝胶相比，KGluc定性地减缓了伤口的初始闭合，并导致组织更接近成熟、健康的皮肤（表皮厚度和真皮 - 表皮形态）。与未加载的水凝胶相比，KGluc治疗显著减少了真皮内肌成纤维细胞的数量，同时上调了血管密度，这可能是TGFβ1信号传导中断的结果。综上所述，这些数据证明了KGluc治疗对皮肤伤口愈合的有效性，并表明这可能是一种限制瘢痕形成的有效治疗方法。
