Background Hypertrophic scars cause impaired skin appearance and function, seriously affecting physical and mental health. Due to medical ethics and clinical accessibility, the collection of human scar specimens is frequently restricted, and the establishment of scar experimental animal models for scientific research is urgently needed. The four most commonly used animal models of hypertrophic scars have the following drawbacks: the rabbit ear model takes a long time to construct; the immunodeficient mouse hypertrophic scar model necessitates careful feeding and experimental operations; female Duroc pigs are expensive to purchase and maintain, and their large size makes it difficult to produce a significant number of models; and mouse scar models that rely on tension require special skin stretch devices, which are often damaged and shed, resulting in unstable model establishment. Our group overcame the shortcomings of previous scar animal models and created a new mouse model of hypertrophic scarring induced by suture anchoring at the wound edge. Methods We utilized suture anchoring of incisional wounds to impose directional tension throughout the healing process, restrain wound contraction, and generate granulation tissue, thus inducing scar formation. Dorsal paired incisions were generated in mice, with wound edges on the upper back sutured to the rib cage and the wound edges on the lower back relaxed as a control. Macroscopic manifestation, microscopic histological analysis, mRNA sequencing, bioinformatics, and in vitro cell assays were also conducted to verify the reliability of this method. Results Compared with those in relaxed controls, the fibrotic changes in stretched wounds were more profound. Histologically, the stretched scars were hypercellular, hypervascular, and hyperproliferative with disorganized extracellular matrix deposition, and displayed molecular hallmarks of hypertrophic fibrosis. In addition, the stretched scars exhibited transcriptional overlap with mechanically stretched scars, and human hypertrophic and keloid scars. Phosphatidylinositol 3-kinase-serine/threonine-protein kinase B signaling was implicated as a profibrotic mediator of apoptosis resistance under suture-induced tension. Conclusions This straightforward murine model successfully induces cardinal molecular and histological features of pathological hypertrophic scarring through localized suture tension to inhibit wound contraction. The model enables us to interrogate the mechanisms of tension-induced fibrosis and evaluate anti-scarring therapies.

中文翻译：

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缝合锚定的皮肤张力在一种新的小鼠模型中诱导持续的增生性瘢痕形成


背景 增生性疤痕会导致皮肤外观和功能受损，严重影响身心健康。由于医学伦理和临床可及性，人类瘢痕标本的采集经常受到限制，迫切需要建立用于科学研究的瘢痕实验动物模型。增生性瘢痕最常用的四种动物模型具有以下缺点：兔耳模型需要很长时间才能构建;免疫缺陷小鼠增生性疤痕模型需要仔细喂养和实验操作;雌性杜洛克猪的购买和维护成本很高，而且它们的大尺寸使其难以生产大量模型;而依赖张力的小鼠疤痕模型需要特殊的皮肤拉伸装置，这些装置经常会损坏和脱落，导致模型建立不稳定。我们小组克服了以往疤痕动物模型的缺点，创造了一种新的由缝合线锚定在伤口边缘诱导的增生性疤痕小鼠模型。方法 我们利用切口伤口的缝合锚固在整个愈合过程中施加定向张力，抑制伤口收缩，并产生肉芽组织，从而诱导瘢痕形成。在小鼠中产生背对切口，上背部的伤口边缘缝合到胸腔，下背部的伤口边缘作为对照放松。还进行了宏观表现、微观组织学分析、mRNA 测序、生物信息学和体外细胞测定以验证该方法的可靠性。结果 与松弛对照组相比，拉伸伤口的纤维化变化更为严重。 组织学上，拉伸的疤痕为细胞增多、血管增生和高增生，细胞外基质沉积杂乱无章，并显示出增生性纤维化的分子特征。此外，拉伸的疤痕与机械拉伸的疤痕以及人类增生性和瘢痕疙瘩表现出转录重叠。磷脂酰肌醇 3-激酶-丝氨酸/苏氨酸-蛋白激酶 B 信号传导被认为是缝合诱导张力下细胞凋亡抵抗的促纤维化介质。结论 这种简单的小鼠模型通过局部缝合张力成功诱导病理增生性瘢痕形成的主要分子和组织学特征，从而抑制伤口收缩。该模型使我们能够询问紧张性诱发纤维化的机制并评估抗疤痕疗法。