title: Mechanical offloading of incisional wounds is associated with transcriptional downregulation of inflammatory pathways in a large animal model.
abstract: 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.
authors.affiliation: Department of Surgery; Division of Plastic and Reconstructive Surgery; Stanford University School of Medicine; Stanford, CA USA.
authors.forename: Michael
authors.initials: M
authors.lastname: Januszyk
authors.affiliation: Department of Surgery; Division of Plastic and Reconstructive Surgery; Stanford University School of Medicine; Stanford, CA USA.
authors.forename: Victor W
authors.initials: VW
authors.lastname: Wong
authors.affiliation: Department of Surgery; Division of Plastic and Reconstructive Surgery; Stanford University School of Medicine; Stanford, CA USA.
authors.forename: Kirit A
authors.initials: KA
authors.lastname: Bhatt
authors.affiliation: Department of Surgery; Division of Plastic and Reconstructive Surgery; Stanford University School of Medicine; Stanford, CA USA.
authors.forename: Ivan N
authors.initials: IN
authors.lastname: Vial
authors.affiliation: Department of Surgery; Division of Plastic and Reconstructive Surgery; Stanford University School of Medicine; Stanford, CA USA.
authors.forename: Josemaria
authors.initials: J
authors.lastname: Paterno
authors.affiliation: Department of Surgery; Division of Plastic and Reconstructive Surgery; Stanford University School of Medicine; Stanford, CA USA.
authors.forename: Michael T
authors.initials: MT
authors.lastname: Longaker
authors.affiliation: Department of Surgery; Division of Plastic and Reconstructive Surgery; Stanford University School of Medicine; Stanford, CA USA.
authors.forename: Geoffrey C
authors.initials: GC
authors.lastname: Gurtner
mesh_terms: D000818:Animals; D004195:Disease Models, Animal; D015536:Down-Regulation / Q000235:genetics*; D053263:Gene Regulatory Networks; D007249:Inflammation / Q000235:genetics* / Q000473:pathology; D020411:Oligonucleotide Array Sequence Analysis; D015398:Signal Transduction / Q000235:genetics*; D034421:Sus scrofa; D014158:Transcription, Genetic; D014945:Wound Healing / Q000235:genetics*; D014947:Wounds and Injuries / Q000235:genetics* / Q000473:pathology
keywords: gene expression; mechanotransduction; microarray; pathway analysis; pig; scarring; wound healing
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