Department of Mechanical Engineering, Korea Advanced Institute of Science and Technology, Daejeon, Republic of Korea.
School of Medicine, Konkuk University, Seoul, Republic of Korea.
Sci Rep. 2019 Nov 5;9(1):16070. doi: 10.1038/s41598-019-52523-9.
Normal healing of skin wounds involves a complex interplay between many different cellular constituents, including keratinocytes, immune cells, fibroblasts, myofibroblasts, as well as extracellular matrices. Especially, fibroblasts play a critical role in regulating the immune response and matrix reconstruction by secreting many cytokines and matrix proteins. Myofibroblasts, which are differentiated form of fibroblasts, feature high cellular contractility and encourage the synthesis of matrix proteins to promote faster closure of the wounds. We focus on the functional characteristics of these myofibroblasts as the healing strategy for severe wounds where the surplus amount of matrix proteins could be beneficial for better regeneration. In this study, we first employed multiple physicochemical cues, namely topographical alignment, TGF-β1, and electrical field (EF), to induce differentiation of dermal fibroblasts into myofibroblasts, and to further activate the differentiated cells. We then used these cells in a mouse wound model to verify their potential as a transplantable substitute for the severe wound. Our results confirmed that physicochemically stimulated myofibroblasts promoted faster healing of the wound compared to the case with non-stimulated myofibroblasts through elevated matrix reconstruction in the mouse model. Conclusively, we propose the utilization of physicochemically tuned myofibroblasts as a novel strategy for promoting better healing of moderate to severe wounds.
皮肤伤口的正常愈合涉及许多不同细胞成分之间的复杂相互作用，包括角质形成细胞、免疫细胞、成纤维细胞、肌成纤维细胞以及细胞外基质。特别是，成纤维细胞通过分泌许多细胞因子和基质蛋白在调节免疫反应和基质重建中起着关键作用。肌成纤维细胞是成纤维细胞的分化形式，具有高细胞收缩性，并鼓励基质蛋白的合成，以促进伤口更快愈合。我们专注于这些肌成纤维细胞的功能特性，作为治疗严重伤口的愈合策略，其中过量的基质蛋白可能有利于更好的再生。在这项研究中，我们首先采用多种物理化学线索，即拓扑排列、TGF-β1 和电场 (EF)，诱导真皮成纤维细胞分化为肌成纤维细胞，并进一步激活分化后的细胞。然后，我们将这些细胞用于小鼠伤口模型，以验证它们作为严重伤口可移植替代物的潜力。我们的结果证实，与未受刺激的肌成纤维细胞相比，物理化学刺激的肌成纤维细胞通过在小鼠模型中提高基质重建，促进了伤口更快的愈合。总之，我们提出利用物理化学调谐的肌成纤维细胞作为促进中度至重度伤口更好愈合的新策略。
