Hypertrophic Scarring After Partial-Thickness Wounds

烧伤和深度皮肤损伤后的增生性疤痕与30年前一样是一个巨大的社会负担。其原因包括：1)没有经过验证的动物模型；2)一般使用非特异性的瘢痕组织匀浆样本，而不考虑组织学或标本年龄。我们提出了两种研究增生性瘢痕的探索性方法，可能会提供相关的临床数据。首先，30年前描述了雌性杜洛克猪的疤痕模型，但从未详细探讨过。我们已经开发了一个五步法来验证该模型，并发现该模型可能类似于人类的增生性瘢痕。其次，皮肤锥体从皮下组织延伸到皮肤表面。它们在一百多年前就被描述过，但也被忽视了。我们重新检查了锥体，发现它们发生在增生性瘢痕发生的相同位置，从而暗示了两者之间的关系。假设-基于这些前提，我们假设雌性红色杜洛克猪身上的厚厚疤痕是一种 这是一种有效的增生性瘢痕模型，可用于确定在增生性瘢痕形成过程中，皮肤圆锥体是否是促纤维化信号或纤维化的来源。具体目标#1-完成雌性杜洛克猪人类增生性瘢痕模型的验证。 我们将比较肥大细胞计数，胶原结节的存在，以及对雌性杜洛克猪和人类增生性瘢痕中胶原结构的透射电子显微镜研究，并与文献进行比较。具体目标#2-确定皮肤圆锥体中的基因表达模式是否表明这些结构在杜洛克雌性动物瘢痕形成过程中的促纤维化信号或纤维化中发挥作用。我们将从浅层和深层杜洛克伤口中激光捕获显微切割锥体，提取并扩增mRNA，并进行猪DNA阵列分析，以确定哪些基因存在差异表达。

Hypertrophic scarring after burns and deep dermal injuries is as large a societal burden as it was 30 years ago. The reasons include 1) no validated animal model and 2) general use of non-specific homogenized samples of scar tissue without regard for histology or specimen age. We propose two exploratory approaches to studying hypertrophic scar that may provide relevent clinical data. First, the female, Duroc pig model of scarring was described 30 years ago but never explored in detail. We have developed a five-step method to validate the model and find that the model may be similar to hypertrophic scarring in humans. Second, the cones of skin extend from the hypodermis to the skin surface. They were described over one hundred years ago but have also been ignored. We have revisited the cones and found that they occur in the same locations that hypertrophic scar occurs thus suggesting a relationship. Hypothesis - Based on these premises we hypothesize that thick scar in the female, red Duroc pig is a valid model of hypertrophic scarring and can be used to determine whether the cones of skin are the source of profibrogenic signals or fibrosis during hypertrophic scarring. Specific Aim #1 - To complete the validation of the female Duroc pig model of human, hypertrophic scar. We will compare mast cell counts, the presence of collagen nodules, and transmission electron microscopy studies of collagen structure in scar of the female Duroc pig to human hypertrophic scar and to the literature. Specific Aim #2 - To determine whether gene expression patterns in cones of skin suggest a role for these structures in profibrogenic signaling or fibrosis during scarring in the female Duroc. We will laser capture microdissect cones from shallow and deep partial-thickness Duroc wounds, extract and amplify the mRNA, and perform porcine DNA array analysis to determine which genes are differentially expressed.