Metalloproteinase expression is associated with traumatic wound failure.
BACKGROUND
Matrix metalloproteinases (MMPs) are crucial in the inflammatory and remodeling phases of wound healing. We previously reported the correlation between pro-inflammatory cytokines and timing of successful combat-wound closure. We now extend our studies to investigate the correlation between wound-remodeling MMP expression and wound healing.


METHODS
Thirty-eight wounds in 25 patients with traumatic extremity combat wounds were prospectively studied. Surgical debridement with vacuum-assisted closure (VAC) device application was repeated every 48 to 72h until surgical wound closure. Wound effluent and patient serum were collected at each wound debridement and analyzed for five matrix metalloproteinases using the Luminex multiplex system; Millipore Corp, Billerica, MA. The primary outcome was wound healing within 30 d of definitive wound closure. Impairment was defined as delayed wound closure (>21 d from injury) or wound dehiscence. MMP expression was compared between impaired and normal healing wounds.


RESULTS
Elevated levels of serum MMP-2 and MMP-7 and reduced levels of effluent MMP3 were seen in impaired wounds (n = 9) compared with wounds that healed (n = 29; P<0.001). Receiver operating characteristic (ROC) curve analysis yielded area-under-the-curve (AUC) of 0.744, 0.783, and 0.805, respectively.


CONCLUSIONS
Impaired wound healing is characterized by pro-inflammatory MMP-2 and MMP-7. Serum and effluent concentrations of MMP-2, MMP-3, and MMP-7 can effectively predict the outcome of traumatic war wounds and can potentially provide decision-supportive, objective evidence for the timing of wound closure.
Utz
Edward R
ER
Regenerative Medicine Department, Combat Casualty Care, Naval Medical Research Center, Silver Spring, Maryland 20910, USA.
Elster
Eric A
EA
Tadaki
Douglas K
DK
Gage
Frederick
F
Perdue
Philip W
PW
Forsberg
Jonathan A
JA
Stojadinovic
Alexander
A
Hawksworth
Jason S
JS
Brown
Trevor S
TS
D000293:Adolescent; D000328:Adult; D000671:Amputation, Surgical / Q000706:statistics & numerical data; D003646:Debridement; D005260:Female; D006801:Humans; D008297:Male; D020778:Matrix Metalloproteinase 2 / Q000235:genetics; D019278:Matrix Metalloproteinase 3 / Q000235:genetics; D020783:Matrix Metalloproteinase 7 / Q000235:genetics; D020782:Matrix Metalloproteinases / Q000235:genetics*; D008887:Military Medicine / Q000379:methods; D011446:Prospective Studies; D014945:Wound Healing / Q000502:physiology*; D014947:Wounds and Injuries / Q000201:enzymology* / Q000235:genetics / Q000601:surgery; D014950:Wounds, Penetrating / Q000201:enzymology; D055815:Young Adult
D020782:Matrix Metalloproteinases; D019278:Matrix Metalloproteinase 3; D020783:Matrix Metalloproteinase 7; D020778:Matrix Metalloproteinase 2