Poor wound healing is a poorly understood complication of diabetes. Our previous data in wound fluids from diabetic subjects have shown that increased MMP-9 activity is associated with delayed wound healing and increased MMP-9 activation is related to greater bacterial load. In this study the effect of diabetes on inflammatory cell and wound fluid MMP-9 was examined in a sterile sponge implant wounding model. The expression of CD147 an MMP regulator and the ability of doxycycline to inhibit MMP-9 were also investigated.

Diabetes was induced in male Sprague-Dawley rats (D:n=17, STZ:65mg/kg). After 6 weeks, four linear incisions were made on the dorsum and 1cm² sponges were implanted subcutaneously. Similarly treated non-diabetic (C:n=6) rats acted as controls. At surgery all animals received a single dose of ampicillin (50mg/kg) and some of the diabetic animals (n=9) were administered oral doxycycline (100mg, daily). After 3 and 6 days, the animals were sacrificed, the sponges were removed and the wound fluids (WF) and cells separated. Wound fluid MMP-9 and -2 (pro and active forms) were detected by zymography and gene expression of MMP-9 and CD147 were measured by RT-qPCR.

Similar to our patient studies but in the absence of signs of clinical infection, diabetes significantly (P<0.05) increased WF total MMP-9 (D:1.71 ± 0.55, C:0.80 ± 0.15ng/μl), activeMMP-9 (D:0.86 ± 0.17, C:0.39 ± 0.07ng/μl), and CD147 mRNA (2 fold). In all groups doxycycline increased WF total and active MMP-9 and had no effect on CD147.  Further investigation is required to elucidate the role of CD147, the cell type responsible for these changes and how doxycycline can alter MMP-9 activities. Whether a submicrobial dose of doxycycline has a similar effect and can improve wound healing rate in an excisional wound model remains to be investigated. Supported by Australian Rotary Health and Rotary Club District 9680, NH&MRC.