Expression of matrix metalloproteinases and growth factors in diabetic foot wounds treated with a protease absorbent dressing.
Wound healing in diabetes is impaired, and nonhealing ulceration represent clinically relevant complications. Persistently high levels of matrix metalloproteases (MMPs) contribute to wound chronicity. Thus, the topical use of protease inhibitors might influence wound healing and promote transition from a chronic to an acute wound.


METHODS
In this study, 33 patients with chronic diabetic foot lesions (stage 2a of the University of Texas Wound Classification system) were included. Fifteen patients received redundant "good standard wound care." In addition, 18 patients were treated with a protease inhibitory modulating matrix (the OCR/collagen Promogran matrix, Ethicon) with dressings changed on a daily basis. Prior to treatment and at 4 and 8 days after treatment, two 3-mm punch biopsies were taken from the center of the wounds and analyzed using ELISA techniques for MMPs, tissue inhibitor of MMP-2 (TIMP-2), and interleukin-1beta (IL-1beta) levels. In addition, mRNA levels of MMPs as well as IL-1beta and TNF-alpha were detected using quantitative real-time polymerase chain reaction (TaqMan, Applied Biosystems, Weiterstadt, Germany).


RESULTS
No differences were detected between both groups and at the three time points for the mRNA levels of MMPs as well as of IL-1beta and TNF-alpha. In addition, MMP levels in wound tissue (analyzed by ELISA) were also not significantly different between both groups. However, IL-1beta was increased on day 8 in the treatment group (P=.01) only. Interestingly, we found a significant reduction of the MMP-9/TIMP-2 ratio in the group being treated with the ORC/collagen. These wounds exhibited a more rapid healing rate when treated with the ORC/collagen matrix.


CONCLUSIONS
The local treatment with a protease inhibitor has a beneficial effect on wound healing. In contrast to the data on wound fluid, our study demonstrated for the first time the unaltered mRNA levels of MMPs during treatment with a protease inhibitory modulating matrix. At the cellular level, MMPs were also not statistically different. However, the more relevant ratio of MMP-9/TIMP-2 was decreased in the treatment group. An equally important finding was that we did not detect a compensatory increase in the MMP-RNA expression even though wound size was clearly reduced.
Lobmann
Ralf
R
Department of Endocrinology and Metabolism, Magdeburg University Medical School, Magdeburg, Germany.
Zemlin
Carola
C
Motzkau
Markus
M
Reschke
Kirsten
K
Lehnert
Hendrik
H
D041342:Absorbent Pads; D000042:Absorption; D000287:Administration, Topical; D000368:Aged; D001458:Bandages; D001672:Biocompatible Materials / Q000008:administration & dosage / Q000627:therapeutic use; D002482:Cellulose / Q000008:administration & dosage / Q000627:therapeutic use; D002483:Cellulose, Oxidized / Q000008:administration & dosage / Q000627:therapeutic use; D003094:Collagen / Q000008:administration & dosage / Q000627:therapeutic use; D017719:Diabetic Foot / Q000201:enzymology / Q000378:metabolism / Q000628:therapy*; D006801:Humans; D007378:Interleukins / Q000235:genetics / Q000378:metabolism; D020782:Matrix Metalloproteinases / Q000235:genetics / Q000378:metabolism*; D008875:Middle Aged; D011480:Protease Inhibitors / Q000627:therapeutic use*; D012333:RNA, Messenger / Q000032:analysis; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics / Q000378:metabolism*; D014945:Wound Healing / Q000502:physiology*
D001672:Biocompatible Materials; D002483:Cellulose, Oxidized; D007378:Interleukins; D011480:Protease Inhibitors; D012333:RNA, Messenger; D014409:Tumor Necrosis Factor-alpha; D002482:Cellulose; D003094:Collagen; D020782:Matrix Metalloproteinases