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Doxycycline-coated sutures improve mechanical strength of intestinal anastomoses
Linköping University, Department of Clinical and Experimental Medicine, Orthopaedics and Sports Medicine . Linköping University, Faculty of Health Sciences.
Malmö University Hospital.
University of Copenhagen.
Copenhagen University Hospital.
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2008 (English)In: International Journal of Colorectal Disease, ISSN 0179-1958, Vol. 23, no 3, 271-276 p.Article in journal (Refereed) Published
Abstract [en]

Background and aims: After resection and repair of the intestines, tissue degradation leads to weakening of the repair site and a risk of postoperative leakage. Matrix metalloproteinases (MMPs) are thought to be responsible for collagenolysis in the direct vicinity of surgical sutures in many tissues. Several experimental studies show that MMP-inhibitors administered systemically alleviate postoperative weakening of intestinal anastomoses. We hypothesised that local delivery of MMP-inhibitors would achieve a similar effect.

Methods: Implementing a novel method for the coating of biomaterials, we coated sutures with a crosslinked fibrinogen film and bound the MMP-inhibitor doxycycline into this film. The sutures were then used in a standard rat model for evaluating mechanical properties of colonic anastomoses 3 days after surgery.

Results: The breaking strength of the anastomoses on the critical third day after operation was 17 % higher with doxycycline-coated sutures compared to controls (P=0.026). Energy uptake at failure was enhanced by 20 % (P=0.047).

Conclusion: Drug delivery by means of MMP-inhibitor-coated sutures appears to improve tissue integrity during anastomotic repair and may reduce postoperative complications.

Place, publisher, year, edition, pages
2008. Vol. 23, no 3, 271-276 p.
Keyword [en]
colon, matrix metalloproteinase (MMP), wound dehiscence, anastomotic leakage, suture
National Category
Medical and Health Sciences
URN: urn:nbn:se:liu:diva-11695DOI: 10.1007/s00384-007-0401-0OAI: diva2:18119
The original publication is available at Björn Pasternak, Martin Rehn, Line Andersen, Magnus S. Ågren, Anne-Marie Heegaard, Pentti Tengvall and Per Aspenberg, Doxycycline-coated sutures improve mechanical strength of intestinal anastomoses, 2008, International Journal of Colorectal Disease, (23), 271-276 Copyright: Springer, www.springerlink.comAvailable from: 2008-09-01 Created: 2008-09-01 Last updated: 2009-08-20
In thesis
1. Towards surgical use of matrix metalloproteinase biology
Open this publication in new window or tab >>Towards surgical use of matrix metalloproteinase biology
2008 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

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
National Category
urn:nbn:se:liu:diva-11489 (URN)978-91-7393-931-7 (ISBN)
Public defence
2008-05-09, Linden, Hälsonuniversitetet, Linköping, 13:30 (English)
Available from: 2008-05-07 Created: 2008-05-07 Last updated: 2015-11-19

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Pasternak, BjörnTengvall, PenttiAspenberg, Per
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Orthopaedics and Sports Medicine Faculty of Health SciencesApplied Physics The Institute of TechnologyDepartment of Orthopaedics Linköping
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