title: Cryo-Induced Thermal Wounds: A Human Acute Wound Model.
abstract: BACKGROUND
  Clinical models are invaluable in studying wound healing. Challenges in studying human wounds include heterogeneity of patients and wounds, as well as prolonged study time, resulting in high costs. Animal models are an efficient method to study wound healing, but often lack correlation with human acute wound healing. Human wound models can be created using sharp instruments, suction, acids, heat and cold. In this observational study, we propose a practical human acute wound model where partial thickness wounds are induced by cryosurgery to create wounds that could facilitate wound healing research and development.
  
  
  METHODS
  On forearms of 8 healthy adult volunteers, freeze injuries were induced using liquid nitrogen spray delivered onto a target area of a 1 cm circular opening at a distance from the cryo-device to the skin of 0.5-1 cm. Several freeze-thaw time cycles were implemented by administering pulses ranging from 3 to 12 seconds. Clinical evaluation was performed at a 24-hour follow-up period. Blister roofs were histologically analyzed by a blinded dermatophathologist. Clinical assessment of time to heal was determined.
  
  
  RESULTS
  Freeze-times greater than 5 seconds caused a majority of subjects to develop blisters, and freeze-times greater than 8 seconds resulted in uniform blister formation. Consistent histology of full thickness necrotic epidermis with intact detached basement membrane with minimal acute neutrophilic inflammatory infiltrate was observed in all blister specimens examined. The 8-second freeze-time group had a time to heal of 13-14 days, while the 12-second freeze-time group required 3 weeks to heal. After healing, an area of hypopigmented skin and slightly hypertrophic scarring remained.
  
  
  CONCLUSIONS
  This novel cryo-induced wound model is a potential simple, efficient and reliable model for studying the dynamic processes involved in acute wound healing and to aid in the development of new wound healing therapies. Clinicaltrials.gov identifier: NCT01253135.
authors.forename: Alejandra
authors.initials: A
authors.lastname: Vivas
authors.forename: Joshua D
authors.initials: JD
authors.lastname: Fox
authors.forename: Katherine L
authors.initials: KL
authors.lastname: Baquerizo Nole
authors.forename: Andrea D
authors.initials: AD
authors.lastname: Maderal
authors.forename: Evangelos
authors.initials: E
authors.lastname: Badiavas
authors.forename: D Innes
authors.initials: DI
authors.lastname: Cargill
authors.forename: Herbert B
authors.initials: HB
authors.lastname: Slade
authors.forename: Steven R
authors.initials: SR
authors.lastname: Feldman
authors.forename: Robert S
authors.initials: RS
authors.lastname: Kirsner
mesh_terms: D000328:Adult; D001768:Blister / Q000209:etiology / Q000473:pathology; D003452:Cryosurgery / Q000379:methods*; D006801:Humans; D012867:Skin / Q000293:injuries* / Q000473:pathology; D014945:Wound Healing