Towards surgical use of matrix metalloproteinase biology
2008 (English)Doctoral thesis, comprehensive summary (Other academic)
Matrix metalloproteinases (MMPs), such as collagenases, are a family of enzymes capable of degrading most constituents of the extracellular matrix. MMPs are thought to be involved in the aetiopathogenesis of tendon rupture. Additionally, failure of healing has in some instances been associated with elevated levels of MMPs. We have studied (a) the effects of the MMP-inhibitor doxycycline on healing of tendons and intestines in experimental models and (b) systemic levels of MMPs and their endogenous inhibitors (TIMPs) in patients with tendon rupture.
In the first study, systemic doxycycline treatment lead to weakened rat Achilles tendons during healing after injury.
Subsequently, systemic doxycycline was shown to improve biomechanical properties of tendon suture fixation in the rat Achilles tendon. Sutures were also coated with doxycycline, leading to similar improvement in mechanical strength of the suture construct during healing.
In the third study, doxycycline-coated sutures improved the strength of healing intestinal anastomoses in an experimental model.
Finally, we showed that patients with a history of Achilles tendon rupture had elevated levels of MMP-2, MMP-7 and TIMP-2 in serum. In addition, MMP-7 correlated inversely to mechanical strength of the tendon during healing.
In conclusion, MMP-inhibitors can be administered systemically and locally to manipulate healing of tendons and intestines. Generalised alterations in the MMP-TIMP system may be involved in the pathogenesis of Achilles tendon rupture and associated with differences in outcome of healing.
Place, publisher, year, edition, pages
Linköping University Electronic Press, 2008. , 61 p.
Linköping University Medical Dissertations, ISSN 0345-0082 ; 1057
Achilles tendon, colon, tetracyclines, tissue inhibitor of metalloproteinases (TIMP), wound healing., colorectal surgery, extracellular matrix, humans, matrix metalloproteinases (MMPs), rats, surgical anastomosis, sutures, tendon injuries
IdentifiersURN: urn:nbn:se:liu:diva-11489ISBN: 978-91-7393-931-7OAI: oai:DiVA.org:liu-11489DiVA: diva2:17919
2008-05-09, Linden, Hälsonuniversitetet, Linköping, 13:30 (English)
Konttinen, Yrjö T, Professor
Aspenberg, PerTengvall, Pentti
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