Understanding the role of skin mechanical properties in the formation of scars.

了解皮肤机械特性在疤痕形成中的作用。

• 批准号: NE/T014415/1
• 负责人: Claire Higgins
• 金额: $ 1.33万
• 依托单位: Imperial College London
• 依托单位国家: 英国
• 项目类别: Research Grant
• 财政年份: 2020
• 资助国家: 英国
• 起止时间: 2020 至 无数据
• 项目状态: 已结题
• 来源: https://gtr.ukri.org/projects?ref=NE%2FT014415%2F1
• 关键词: Understanding; role; skin; mechanical; properties

MRC : Magdalena Plotczyk : MR/N014103/1Scarring is a common consequence of burn injuries and surgical procedures, placing an enormous burden on individuals and the society. An estimated 100 million people per year in the developed world alone suffer from excessive scarring. Patients suffer from long-term physical dysfunction in the form of painful contractures or psychological harm from social stigma. Multiple surgical techniques have been tried to minimize scarring, but so far there is no proven method to prevent scar formation. To address this clinical need, the present study aims to increase our understanding of the role of skin tension in dermal fibrosis and the heterogeneity between scars, which range from unpigmented fine lines to widespread pathological scars.Despite differences between scar types, all of them are characterized by increased deposition of collagen fibres and changes in the mechanical properties of the skin. Increased tension on the healing wound is considered to promote scar formation. However, a laxity paradox in the field of hair transplantation describes a phenomenon opposing this view. After a surgery involving removal of tissue from the occipital scalp for harvesting hair follicles, patients with tight scalps heal with narrow 1-2 mm wide scars, while those characterised by loose scalp skin (approx. 5%) obtain 10-12 mm wide stretched scars. Despite the widespread recognition of the laxity paradox amongst hair transplant surgeons, its cellular mechanism remains unknown. In my PhD thesis, I hypothesise that the differences in clinical outcomes - developing a stretched or a neat scar, depend on the underlying mechanical properties of the skin. Despite previous references to stretched scars being formed in areas of extensive tension, in patients with loose skin, the tension of the healing skin may be insufficient to support a healthy level of skin contraction, and thus lead to skin 'stretching' and formation of a wide scar.The results of my PhD thesis so far suggest that decreased presence of certain proteins can serve as a unique signature of stretched scars. In my future experiments, I will test if these changes can be caused by decreased tension applied to the healing wound in the loose skin. At the University of Toronto, I will use the expertise and facilities of the host lab to expose skin cells to different mechanical forces and record their response. Upon completion of these experiments, I will know whether the lower tension across a healing wound in loose skin has a role in decreased protein expression and stretched scar formation. In the long term, the study will validate targets for therapeutic intervention to reduce scar formation or revise established scars, leading to both economic and societal impact.

MRC：Magdalena Plotczyk：MR/N014103/1烧伤是烧伤和外科手术的常见后果，给个人和社会带来巨大负担。据估计，仅在发达国家，每年就有1亿人遭受过度疤痕之苦。患者患有长期的身体功能障碍，表现为疼痛的痉挛或因社会耻辱而造成的心理伤害。已经尝试了多种手术技术来尽量减少疤痕，但到目前为止还没有被证明有效的方法来防止疤痕的形成。为了解决这一临床需要，本研究旨在增加我们对皮肤张力在真皮纤维化中的作用以及瘢痕之间的异质性的了解，这些瘢痕从无色素细纹到广泛的病理性瘢痕。尽管不同类型的瘢痕存在差异，但它们的特征都是胶原纤维沉积增加和皮肤机械性能的变化。愈合伤口上的张力增加被认为是促进疤痕形成的原因。然而，头发移植领域的一种松弛悖论描述了一种反对这一观点的现象。在切除枕部头皮组织以获取毛囊的手术后，头皮紧密的患者愈合时会留下1-2毫米宽的狭窄疤痕，而以头皮松弛为特征的患者则会愈合。5%)获得10-12 mm宽的拉伸疤痕。尽管人们普遍认识到头发移植外科医生之间的松弛悖论，但其细胞机制仍不清楚。在我的博士论文中，我假设临床结果的差异--形成伸展的或整齐的疤痕--取决于皮肤的潜在机械性能。尽管之前提到的拉伸疤痕是在广泛紧张的区域形成的，但在皮肤松弛的患者中，愈合皮肤的张力可能不足以支撑健康的皮肤收缩，从而导致皮肤拉伸并形成广泛的疤痕。到目前为止，我的博士论文结果表明，某些蛋白质的减少可以作为拉伸疤痕的独特标志。在我未来的实验中，我将测试这些变化是否可以由应用于松弛皮肤愈合伤口的张力减少引起。在多伦多大学，我将利用主办实验室的专业知识和设施，让皮肤细胞暴露在不同的机械力下，并记录它们的反应。在完成这些实验后，我将知道在松弛的皮肤上愈合的伤口上的较低张力是否在蛋白质表达减少和伸展的疤痕形成中起作用。从长远来看，这项研究将验证治疗干预的目标，以减少疤痕形成或修正已形成的疤痕，从而产生经济和社会影响。