ORGINAL ARTICLE–BASIC SCIENCE Modulation of scarring in a liquid environment in the Yorkshire pig Richard G. Reish, MD; Baraa Zuhaili, MD; Juri Bergmann, MD; Pejman Aflaki, MD; Taro Koyama, MD; Florian Hackl, MD; Emily Waisbren, BA; Jose A. Canseco, MD; Kapil D. Verma, MD; Elof Eriksson, MD, PhD; Feng Yao, PhD Division of Plastic Surgery, Brigham and Women’s Hospital, Harvard Medical School, Boston, Massachusetts Reprint requests: Elof Eriksson, Division of Plastic Surgery, Brigham and Women’s Hospital, Harvard Medical School, 75 Francis St., Boston, MA 02115. Tel: 11 617 732 7409; Fax: 11 617 732 6387; Email: eeriksson@partners.org Manuscript received: December 24, 2008 Accepted in final form: July 28, 2009 DOI:10.1111/j.1524-475X.2009.00546.x ABSTRACT Decreased inflammatory response seen in wet wound healing may be correlated with diminished scarring. This study seeks to test this hypothesis and to validate a model of scarring in the Yorkshire pig. Four Yorkshire pigs were used to create 36 dorsal wounds per pig (144 wounds total) in the following groups: full-thick- ness excisional, partial thickness, meshed split-thickness skin grafts, sheet split- thickness skin grafts, minced skin, and incisional wounds. Wounds were ran- domized into wet and dry groups. Wet wounds were enclosed in polyurethane chambers with 2 mL of normal saline. Dry wounds were covered with regular gauze. Terminal biopsies were performed at 72 hours and day 28. Histology dem- onstrated significantly less inflammatory infiltrate, thicker neoepidermis, more pronounced rete ridge formation, and decreased scar tissue thickness in wet wounds. The mean macroscopic scar surface area was significantly decreased in full-thickness excisional wet wounds compared with dry wounds (61.2 mm 2 vs. 150.8 mm 2 , p < 0.01). Hydroxyproline content was decreased in full-thickness wet compared with dry groups (44.81 vs. 62.21 mg/g, p < 0.01). Tensile strength was 90% greater in full-thickness wet compared with dry groups (p < 0.01). Healing in the liquid environment significantly reduced scar formation. This model will allow for future investigation of high-concentration topical scar-mod- ulating agents in the liquid environment. Despite advancements in knowledge of the mechanisms of wound healing and scar formation, both normal and hypertro- phic scars (HS) remain difficult to treat and impossible to pre- vent. Scarring is a very complicated process involving many different factors with activation through multiple pathways and much of the outcome of scar formation is likely determined by the early inflammatory response to wounding. 1,2 An under- standing of the processes of normal and abnormal scar forma- tion in animal models is paramount to the development of new methodologies to successfully manage and potentially prevent abnormal healing of scars in humans. Investigators have used different animal models including a rabbit ear model, 3 mice, 4,5 rats, 6,7 and pigs 8–10 to study properties of scar formation in the setting of incisional, excisional, and burn models of injury. Wet treatment of wounds with a chamber has been vali- dated in a number of experiments in the Yorkshire pig, whose large size and skin similar to that of humans makes it well suited for preclinical studies of wound healing and scar formation. For the past 15 years, our laboratory has studied wet wound healing with use of a wound chamber that pro- vides a controlled liquid environment. 11 Healing in a liquid environment results in less tissue necrosis, less inflammation, and faster wound healing. 11,12 It has been shown that the wet environment has no adverse effects on porcine or human skin. 13 Porcine partial-thickness 12 and full-thickness wounds 14 exhibit faster rates of reepithelialization in a wet environment compared with a dry environment. The effect of wet wound healing on scar formation using the wound chamber described above has not been studied before. The hypothesis has been raised that decreased in- flammation seen in the liquid environment with use of the wound chamber is correlated with diminished scarring. The present study seeks to test that hypothesis by develop- ing and validating a model of cutaneous scarring in the Yorkshire pig and evaluating the degree to which wet wound healing modulates scar formation. MATERIALS AND METHODS Animals All animal procedures were approved by the Harvard Medical Area Standing Committee on animals. Four Yorkshire pigs, approximately 6 months old and weighing 50–60 kg, were kept in separate, custom-made, smooth- sided, stainless-steel cages to minimize wound trauma and disruption of applied chambers and dressings. Wound creation Excisional wound sites measuring 15 mm  15 mm and in- cisional wound sites measuring 20 mm and separated by at least 4 cm of unwounded skin were outlined along four Wound Rep Reg (2009) 17 806–816 c  2009 by the Wound Healing Society 806 Wound Repair and Regeneration