Age and growth factors in porcine full-thickness wound healing.
It has been recognized that the rate of cutaneous wound healing declines with age, yet the molecular processes that affect this decline remain poorly understood. The purpose of this study was to compare reepithelialization and contraction rates, and growth factor profiles in full-thickness wounds in swine of various ages. Multiple full-thickness excisional wounds were created on the dorsum of 24-month-old (n=2), 4-month-old (n=2), and 2-month-old (n=2) Yucatan Minipigs. The extent of reepithelialization was shown to decrease with increasing age in a manner that was statistically significant among the 2-month-old (79%), 4-month-old (48%), and 24-month-old pigs (22%). Enzyme-linked immunosorbent assay results showed that endogenous vascular endothelial growth factor concentrations in the 2- and 4-month-old animals peaked on day 4, reaching levels of 482 pg/ml and 420 pg/ml, respectively. In the 24-month-old pigs the vascular endothelial growth factor concentration peaked later (day 6), and was present at a lower level (229 pg/ml). On day 4 the vascular endothelial growth factor levels in the older pigs reached only 120 pg/ml, representing a four-fold decrease in concentration compared to the younger pigs. A comparison of platelet-derived growth factor-BB concentrations across the age groups showed similar patterns in the 2- and 4-month-old pigs (peaks of 77 and 91 pg/ml on days 2 and 3, respectively), and levels in the 24-month-old were below the sensitivity level (31.5 pg/ml) of the assay. Transforming growth factor-beta1 levels across the age groups did not differ in a manner that was statistically significant, and all age groups peaked on day 9. Wound contraction showed no statistical differences among the age groups from days 3 to 9. On day 11, however, wound contraction in 2-month-old pigs was about 10% faster than in 24-month-old pigs (p < 0.05). These data suggest a possible new algorithm for treating wounds in aged skin, by which exogenous growth factors can be added to the wound microenvironment in doses and at times that match the growth factor profiles observed in wounds made in younger skin.
Yao
F
F
Laboratory of Wound Repair and Gene Transfer, Division of Plastic Surgery, Brigham and Women's Hospital, Department of Surgery, Harvard Medical School, Boston, MA 02115, USA.
Visovatti
S
S
Johnson
C S
CS
Chen
M
M
Slama
J
J
Wenger
A
A
Eriksson
E
E
D000367:Age Factors; D000818:Animals; D000925:Anticoagulants / Q000032:analysis; D000077214:Becaplermin; D004195:Disease Models, Animal; D016228:Endothelial Growth Factors / Q000032:analysis / Q000502:physiology*; D005260:Female; D008222:Lymphokines / Q000032:analysis / Q000502:physiology*; D010982:Platelet-Derived Growth Factor / Q000032:analysis; D020574:Proto-Oncogene Proteins c-sis; D012867:Skin / Q000293:injuries* / Q000503:physiopathology*; D013556:Swine, Miniature; D013997:Time Factors; D016212:Transforming Growth Factor beta / Q000032:analysis; D053773:Transforming Growth Factor beta1; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors; D014945:Wound Healing / Q000502:physiology*; D014950:Wounds, Penetrating / Q000503:physiopathology*
D000925:Anticoagulants; D016228:Endothelial Growth Factors; D008222:Lymphokines; D010982:Platelet-Derived Growth Factor; D020574:Proto-Oncogene Proteins c-sis; D016212:Transforming Growth Factor beta; D053773:Transforming Growth Factor beta1; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors; D000077214:Becaplermin