Differential effects of platelet-derived growth factor BB in accelerating wound healing in aged versus young animals: the impact of tissue hypoxia.
Platelet-derived growth factor BB (PDGF-BB) plays a central role in wound healing. Platelet-derived growth factor has been shown to accelerate healing in preclinical and clinical studies, but its wound-healing effects in older animals have not been examined. An ischemic incisional model in young female (5 months) and aged male (60 months) rabbits was used to determine the influence of platelet-derived growth factor on day 14 postwounding with reduced blood supply. Wounds in aged ischemic animals were severely impaired in breaking strength compared with their nonischemic control wounds and wounds in young animals (p < 0.001). Topical platelet-derived growth factor (10 microg per wound) partially reversed the reduction in breaking strength in aged ischemic animals but was ineffective in young animals. Histologic studies showed that new granulation tissue deposition and mononuclear cell infiltration was dramatically lower in ischemic wounds of aged animals compared with their control wounds as well as wounds from young animals under both nonischemic and ischemic conditions. Platelet-derived growth factor partially reversed this deficit in old ischemic wounds but not in young ischemic wounds. Epithelial growth was reduced in wounds from aged animals compared with wounds from young animals after 14 days of healing. Platelet-derived growth factor treatment increased ischemic wound epithelial growth in aged ischemic animals about threefold compared with paired controls. In conclusion, wound healing in aged rabbits was severely impaired by ischemia, and a single topical platelet-derived growth factor treatment partially reversed this deficit.
Wu
L
L
Division of Plastic Surgery, Department of Surgery, Northwestern University Medical School, Chicago, Ill., USA.
Brucker
M
M
Gruskin
E
E
Roth
S I
SI
Mustoe
T A
TA
D000375:Aging / Q000502:physiology*; D000818:Animals; D000925:Anticoagulants / Q000627:therapeutic use*; D000077214:Becaplermin; D004431:Ear, External / Q000098:blood supply / Q000293:injuries; D005260:Female; D000860:Hypoxia / Q000503:physiopathology*; D007511:Ischemia / Q000503:physiopathology*; D008297:Male; D010982:Platelet-Derived Growth Factor / Q000627:therapeutic use*; D020574:Proto-Oncogene Proteins c-sis; D011817:Rabbits; D011994:Recombinant Proteins / Q000627:therapeutic use; D013718:Tensile Strength; D014945:Wound Healing / Q000187:drug effects*
D000925:Anticoagulants; D010982:Platelet-Derived Growth Factor; D020574:Proto-Oncogene Proteins c-sis; D011994:Recombinant Proteins; D000077214:Becaplermin