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

MRC：Magdalena Plotczyk：MR/N 014103/1疤痕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1亿人患有过度疤痕。患者遭受长期的身体功能障碍，表现为疼痛的挛缩或社会耻辱造成的心理伤害。多种手术技术已被尝试，以尽量减少疤痕，但到目前为止，还没有被证明的方法，以防止疤痕形成。为了满足这一临床需求，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理解，这些瘢痕的范围从无色素的细纹到广泛的病理性瘢痕，尽管瘢痕类型之间存在差异，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会促进瘢痕形成。然而，在毛发移植领域的松弛悖论描述了一种与这种观点相反的现象。在涉及从枕骨头皮切除组织以收获毛囊的手术后，头皮紧绷的患者愈合时留下狭窄的1-2 mm宽的疤痕，而那些以头皮皮肤松弛为特征的患者（约1 mm宽）愈合时留下疤痕。5%）获得10-12 mm宽的拉伸瘢痕。尽管在毛发移植外科医生中广泛认识到松弛悖论，但其细胞机制仍然未知。在我的博士论文中，我假设临床结果的差异-形成拉伸或整齐的疤痕，取决于皮肤的潜在机械特性。尽管以前提到过在广泛的张力区域形成拉伸疤痕，但在皮肤松弛的患者中，愈合皮肤的张力可能不足以支持健康水平的皮肤收缩，从而导致皮肤“拉伸”并形成宽疤痕。到目前为止，我的博士论文的结果表明，某些蛋白质的存在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松弛皮肤中愈合伤口的张力降低引起。在多伦多大学，我将利用宿主实验室的专业知识和设施，将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，我将知道松弛皮肤中愈合伤口的较低张力是否在蛋白质表达减少和拉伸疤痕形成中起作用。从长远来看，该研究将验证治疗干预的目标，以减少疤痕形成或修改已形成的疤痕，从而产生经济和社会影响。

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.