title: Light-activated sealing of skin wounds.
abstract: OBJECTIVE
  We have developed a light-activated technology for rapidly sealing skin surgical wounds called photochemical tissue bonding (PTB). The goals of this study were to evaluate parameters influencing PTB in order to optimize its clinical efficacy and to determine whether PTB can be used to seal wounds in moderately to highly pigmented skin.
  
  
  METHODS
  Application of Rose Bengal (RB) followed by exposure to 532 nm was used to seal linear incisions (1.5 mm deep, 2 cm long) in lightly pigmented (Yorkshire) and darkly pigmented (Yucatan) swine skin. The force required to open the seal (the bonding strength) was measured by in situ tensiometry. Reflectance spectra, epidermal transmission spectra, and histology were used to characterize the skin. The relationships of RB concentration and fluence to bonding strength were established in Yorkshire skin. Surface temperature was measured during irradiations and cooling was used while sealing incisions in Yucatan skin. Monte Carlo simulations were carried out to estimate the effect of epidermal melanin on the power absorbed in the dermis at the incision interface.
  
  
  RESULTS
  The lowest fluence, 25 J/cm(2), delivered at an irradiance of 0.5 W/cm(2) substantially increased the bonding strength (∼ 10-fold) compared to controls in Yorkshire swine skin. Increasing the fluence to 100 J/cm(2) enhanced bonding strength by a further 1.5-fold. Application of 0.1% RB for 2 minutes produced the greatest bonding strength using 100 J/cm(2) and limited the penetration of RB to an ∼ 50 μm band on the dermal incision wall. Reflectance spectra indicated that Yorkshire skin had minimal melanin and that Yucatan skin was a good model for highly pigmented human skin. In Yucatan skin, the bonding strength increased 1.7-fold using 0.1% RB and 200 J/cm(2) at 1.5 W/cm(2) with cooling and epinephrine. Monte Carlo simulation indicated that absorption of 532 nm light by epidermal melanin in dark skin decreased the power absorbed along the incision in the dermis by a factor of 2.7.
  
  
  CONCLUSIONS
  These results suggest that in lightly pigmented skin the PTB treatment time can be shortened without compromising the bonding strength. Sealing incisions using PTB in moderately and highly pigmented skin will require a careful balance of irradiance and cooling.
authors.affiliation: Wellman Center for Photomedicine, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts; Dermatology Department, Shanghai East Hospital, Tongji University, Shanghai, China.
authors.forename: Nan
authors.initials: N
authors.lastname: Xu
authors.forename: Min
authors.initials: M
authors.lastname: Yao
authors.forename: William
authors.initials: W
authors.lastname: Farinelli
authors.forename: Zeinab
authors.initials: Z
authors.lastname: Hajjarian
authors.forename: Ying
authors.initials: Y
authors.lastname: Wang
authors.forename: Robert W
authors.initials: RW
authors.lastname: Redmond
authors.forename: Irene E
authors.initials: IE
authors.lastname: Kochevar
mesh_terms: D000818:Animals; D015415:Biomarkers / Q000378:metabolism; D001696:Biomechanical Phenomena; D005260:Female; D053844:Lasers, Solid-State / Q000627:therapeutic use*; D008297:Male; D008543:Melanins / Q000378:metabolism; D009010:Monte Carlo Method; D010778:Photochemotherapy / Q000379:methods*; D017319:Photosensitizing Agents / Q000627:therapeutic use*; D012395:Rose Bengal / Q000627:therapeutic use*; D012867:Skin / Q000293:injuries* / Q000378:metabolism / Q000503:physiopathology; D017695:Soft Tissue Injuries / Q000188:drug therapy; D013552:Swine; D058106:Wound Closure Techniques; D014945:Wound Healing / Q000502:physiology
chemical_list: D015415:Biomarkers; D008543:Melanins; D017319:Photosensitizing Agents; D012395:Rose Bengal
keywords: Rose Bengal; Yorkshire swine skin; Yucatan swine skin; epidermal melanin; incision closure; melanin; photo tissue bonding; photochemical tissue bonding; pigmented skin; protein crosslinking; sealing incisions; wound closure