Matrix metalloproteinases in impaired wound healing

Abstract

Cutaneous wound healing is a complex tissue response that requires a coordinated interplay of multiple cells in orchestrated biological processes to finally re-establish the skin's barrier function upon injury. Proteolytic enzymes and in particular matrix metalloproteinases (MMPs) contribute to all phases of the healing process by regulating immune cell influx, facilitating migration of fibroblasts and keratinocytes, and remodeling of the scar tissue. As a result of these pleiotropic functions in the healing skin wound, uncontrolled activities of MMPs are associated with impaired wound healing, a growing health problem in Western countries due to increased life expectancies and rising rates of underlying diseases, such as diabetes. However, detailed mechanisms have been only partially unraveled, and new diagnostic tools and more targeted therapies are urgently needed. In this review, we discuss the roles of MMPs in acute and chronic wound healing and summarize current therapeutic approaches aiming at inhibiting aberrant MMP activities in healing disorders.

Octenidine-based hydrogel shows anti-inflammatory and protease-inhibitory capacities in wounded human skin

“…The fact that OCT inhibits the release of tissue MMPs might be one further explanation of the pathological scar preventing and wound healing promoting effects of OCT in vivo. TIMP-1 is one of the major MMP inhibitors, usually significantly downregulated in chronic or slowly healing wounds 10 . As OCT did not regulate TIMP-1, as revealed by LC–MS and ELISA analysis, the exact mechanism of MMP inhibition by OCT in our model is not yet clear and remains to be further investigated.…”

“…MMP activity is mainly regulated via tissue inhibitors of metalloproteinases (TIMPs) 8 . In chronic wounds or wounds showing delayed wound healing frequently, an imbalance between TIMPs and MMPs has been observed 9 , 10 . Enhanced activity of MMPs might cause increased ECM degradation, alteration of the cytokine profile, and degradation of growth factors, culminating in delayed or absent wound closure 11 .…”

Cellulose/Collagen Dressings for Diabetic Foot Ulcer: A Review

“…On the contrary, the imbalance of collagen synthesis and degradation, especially in diabetic patient’s skin, commonly exhibited severe stiffness with poor flexibility [ 77 ]. In addition, the inflammatory phases of wound healing in diabetic patients were prolonged and the deposition of granulation tissue was hindered, leading to a slow phase in wound healing [ 78 , 79 ]. In a worst-case scenario, DFU patients commonly presented with a high blood glucose level in the body will have altered blood circulation.…”

Selective toxicity of antibacterial agents—still a valid concept or do we miss chances and ignore risks?

“…Few investigators only have analysed enzyme activities or gene expression, whereas MMP concentrations in supernatants of cell cultures have been analysed in most of the studies. A decrease in MMP concentrations as a consequence of antibiotic treatment could be demonstrated in patients with orthopaedic infections treated with ß-lactams [111,112] and daptomycin [113], as well as pulmonary diseases treated with clarithromycin and azithromycin [114,115]; doxycycline reduced MMP concentrations in patients with CF, COPD, and tuberculosis [116][117][118][119], chronic wounds [120][121][122][123][124][125][126][127][128], abdominal aortic aneurysm [129][130][131][132], ophthalmological diseases [133,134], and in patients with acute lung injury following cardiac bypass [135]. Marketing authorizations have been granted for treatment of rosacea and periodontal diseases with sub-antimicrobial doses of doxycycline due to MMP inhibition [136][137][138][139][140][141][142].…”

“…Doxycycline reduced MMP concentrations in patients with CF, COPD, and tuberculosis chronic wounds, abdominal aortic aneurysm, and ophthalmological diseases [116][117][118][119][120][121][122][123][124][125][126][127][128][129][130][131][132][133][134] Anti-neoplastic effects (S2, S3, S50-S56, S62) Commercially available for treatment of rosacea and periodontal diseases [136][137][138][139][140][141][142] Recovery of patients was associated with a decrease in MMP concentrations as a consequence of treatment of orthopaedic indications with ß-lactams [111,112] and daptomycin [113], respiratory infections with macrolides [114,115] Evidence confirming a clinical benefit resulting from MMP-inhibition in patients is lacking for the remaining agents ion in the homologous active centre of the carbonic anhydrase [153,154] pH regulation, HC0…”