title: Transforming growth factor beta 1 improves wound healing and random flap survival in normal and irradiated rats.
abstract: OBJECTIVE
  To evaluate the effect of chronic irradiation on wound healing and random flap survival (FV), and the effect of transforming growth factor beta 1 (TGF-beta 1) in this setting using an animal model.
  
  
  METHODS
  A randomized, controlled study with four groups of rats to study the effect of irradiation 4 months before surgical intervention. The effect of TGF-beta 1 on FV and wound healing also was evaluated in the irradiated and nonirradiated groups.
  
  
  METHODS
  Ninety-five rats were available for evaluation. Group 1 (n = 10) was the control; group 2 (n = 28) received TGF-beta 1; group 3 (n = 28) received radiation therapy; and group 4 (n = 29) received radiation therapy and TGF-beta 1.
  
  
  METHODS
  The irradiated groups received 15 Gy to their dorsal skin. Four months later all received McFarlane skin flaps. Groups 2 and 4 received topical TGF-beta 1, 4 micrograms, to the bed of the flap; groups 1 and 3 received saline. On postoperative day 7 all rats were evaluated for tensile strength and FV, and histologic staining with hematoxylin-eosin for collagen and TGF-beta 1 was done. The slides were evaluated in a "blinded" fashion.
  
  
  RESULTS
  Irradiation decreased tensile strength and FV, but not to a notable degree. Transforming growth factor beta 1 improved tensile strength in the irradiated (P = .04, Student's t test) and nonirradiated groups (P = .05, Student's t test). Transforming growth factor beta 1 also improved FV in all groups, but significantly in the irradiation plus TGF-beta 1 group (P = .001, Student's t test). The TGF-beta 1 group had the most mature collagen present at the wound edge. No qualitative difference was seen in the immunohistochemical staining for the four groups.
  
  
  CONCLUSIONS
  Transforming growth factor beta 1 improves wound healing and random FV in radiated and nonirradiated rat skin. Further study is needed to determine the radiation dose necessary to create an "impaired wound-healing model" in rats, and the optimum dose of TGF-beta 1 in this setting.
authors.affiliation: Department of Otolaryngology, College of Medicine, University of Florida, Gainesville, USA.
authors.forename: A V
authors.initials: AV
authors.lastname: Nall
authors.forename: R E
authors.initials: RE
authors.lastname: Brownlee
authors.forename: C P
authors.initials: CP
authors.lastname: Colvin
authors.forename: G
authors.initials: G
authors.lastname: Schultz
authors.forename: D
authors.initials: D
authors.lastname: Fein
authors.forename: N J
authors.initials: NJ
authors.lastname: Cassisi
authors.forename: T
authors.initials: T
authors.lastname: Nguyen
authors.forename: A
authors.initials: A
authors.lastname: Kalra
mesh_terms: D000287:Administration, Topical; D000818:Animals; D003094:Collagen / Q000032:analysis; D004195:Disease Models, Animal; D004353:Drug Evaluation, Preclinical; D006085:Graft Survival; D007150:Immunohistochemistry; D008297:Male; D011878:Radiotherapy / Q000009:adverse effects*; D011897:Random Allocation; D051381:Rats; D017207:Rats, Sprague-Dawley; D016037:Single-Blind Method; D013524:Surgical Flaps / Q000502:physiology*; D013718:Tensile Strength; D016212:Transforming Growth Factor beta / Q000627:therapeutic use*; D014945:Wound Healing / Q000187:drug effects* / Q000528:radiation effects*
chemical_list: D016212:Transforming Growth Factor beta; D003094:Collagen