Januszyk Michael, Wong Victor W, Bhatt Kirit A, Vial Ivan N, Paterno Josemaria, Longaker Michael T, Gurtner Geoffrey C
Department of Surgery; Division of Plastic and Reconstructive Surgery; Stanford University School of Medicine; Stanford, CA USA.
Organogenesis. 2014 Apr-Jun;10(2):186-93. doi: 10.4161/org.28818. Epub 2014 Apr 16.
Cutaneous scarring is a major source of morbidity and current therapies to mitigate scar formation remain ineffective. Although wound fibrosis and inflammation are highly linked, only recently have mechanical forces been implicated in these pathways. Our group has developed a topical polymer device that significantly reduces post-injury scar formation via the manipulation of mechanical forces. Here we extend these studies to examine the genomewide transcriptional effects of mechanomodulation during scar formation using a validated large animal model, the red Duroc pig. We demonstrate that mechanical loading of incisional wounds upregulates expression of genes associated with inflammatory and fibrotic pathways, and that device-mediated offloading of these wounds reverses these effects. Validation studies are needed to clarify the clinical significance of these findings.
皮肤瘢痕形成是发病的主要原因,目前减轻瘢痕形成的治疗方法仍然无效。尽管伤口纤维化和炎症密切相关,但直到最近机械力才被认为参与了这些途径。我们的团队开发了一种局部聚合物装置,通过操纵机械力显著减少损伤后瘢痕形成。在这里,我们扩展这些研究,使用经过验证的大型动物模型——红色杜洛克猪,来研究瘢痕形成过程中机械调节对全基因组转录的影响。我们证明,切开伤口的机械加载会上调与炎症和纤维化途径相关的基因表达,而该装置介导的这些伤口卸载可逆转这些影响。需要进行验证研究以阐明这些发现的临床意义。