Role of TGF-beta and FGF in the treatment of radiation-impaired wounds using a novel drug delivery system.
BACKGROUND
Despite refinements in radiotherapy, radiation-impaired wound healing continues to be a major source of postoperative morbidity with few treatment options. The application of polypeptide growth factors has been investigated in both the clinical and laboratory settings. The authors used a novel sustained-release delivery system to examine the effect of transforming growth factor (TGF)-beta and fibroblast growth factor (FGF) on radiation-impaired wound healing in a rodent model.


METHODS
Eighty Sprague-Dawley rats underwent dorsal skin surface irradiation of 2500 cGy using a medical linear accelerator producing energy of 6 MeV followed by creation of a full-thickness skin incision. Six groups of 16 animals underwent either sham irradiation (irradiation control); irradiation only; irradiation and unimpregnated delivery system only; or irradiation and either TGF-beta, FGF, or TGF-beta plus FGF combined. Four animals from each group were euthanized at 4, 7, 14, and 28 days, and the harvested specimens underwent ultimate tensile strength testing and histologic evaluation.


RESULTS
All five irradiated groups had significantly lower ultimate tensile strength than the sham-irradiated control group at all time points (p < 0.05), thus validating the authors' model of radiation-impaired wound healing. Functional analysis demonstrated that all three growth factor-treated groups had significantly higher tensile strengths than either of the untreated irradiated groups at 14 days after wounding (p < 0.05). Histologic evaluation of the irradiated groups revealed increased cellularity and more organized collagen architecture of all treated groups when compared with the untreated groups, with the most pronounced differences seen at 7 days and 14 days after wounding.


CONCLUSIONS
This study effectively demonstrates that TGF-beta and FGF act individually and synergistically when delivered locally by means of a sustained release system to improve ultimate tensile strength in an acute postirradiation impaired wound-healing model.
Tattini
Chad
C
Burlington and Worcester, Mass.; Providence, R.I.; and Chicago, Ill. From the Craniofacial Biology and Tissue Engineering Laboratory, Department of Plastic and Reconstructive Surgery, Lahey Clinic Medical Center; Departments of Plastic Surgery and Radiation Oncology, Brown Medical School, Rhode Island Hospital; private practice; and the Center for Tissue Engineering, University of Massachusetts Medical School.
Manchio
Jeffrey
J
Zaporojan
Victor
V
Carderelli
Gene
G
Bonassar
Lawrence
L
Spangenberger
Anthony
A
Weinzweig
Jeffrey
J
D000818:Animals; D003692:Delayed-Action Preparations; D004195:Disease Models, Animal; D016503:Drug Delivery Systems; D005346:Fibroblast Growth Factors / Q000494:pharmacology*; D036341:Intercellular Signaling Peptides and Proteins / Q000494:pharmacology*; D008297:Male; D011832:Radiation Injuries / Q000188:drug therapy*; D051381:Rats; D016212:Transforming Growth Factor beta / Q000494:pharmacology*; D014945:Wound Healing / Q000187:drug effects* / Q000528:radiation effects; D014947:Wounds and Injuries / Q000188:drug therapy*
D003692:Delayed-Action Preparations; D036341:Intercellular Signaling Peptides and Proteins; D016212:Transforming Growth Factor beta; D005346:Fibroblast Growth Factors