Anastomotic leakage is a dreadful complication in colorectal surgery. It has a negative impact on postoperative mortality, long term life quality and oncological results. Nanofibrous polycaprolactone materials have shown pro-healing properties in various applications before. Our team developed several versions of these for healing support of colorectal anastomoses with promising results in previous years. In this study, we developed highly porous biocompatible polycaprolactone nanofibrous patches. We constructed a defective anastomosis on the large intestine of 16 pigs, covered the anastomoses with the patch in 8 animals (Experimental group) and left the rest uncovered (Control group). After 21 days of observation we evaluated postoperative changes, signs of leakage and other complications. The samples were assessed histologically according to standardized protocols. The material was easy to work with. All animals survived with no major complication. There were no differences in intestinal wall integrity between the groups and there were no signs of anastomotic leakage in any animal. The levels of collagen were significantly higher in the Experimental group, which we consider to be an indirect sign of higher mechanical strength. The material shall be further perfected in the future and possibly combined with active molecules to specifically influence the healing process.

Biomedical Center Faculty of Medicine in Pilsen Charles University 301 00 Pilsen Czech Republic

Department of Nonwovens and Nanofibrous Materials Faculty of Textile Engineering Technical University of Liberec 460 01 Liberec Czech Republic

Department of Surgery Faculty of Medicine in Pilsen Charles University 301 00 Pilsen Czech Republic

Zobrazit více v PubMed

Rahbari N.N., Weitz J., Hohenberger W., Heald R.J., Moran B., Ulrich A., Holm T., Wong W.D., Tiret E., Moriya Y., et al. Definition and grading of anastomotic leakage following anterior resection of the rectum: A proposal by the International Study Group of Rectal Cancer. Surgery. 2010;147:339–351. doi: 10.1016/j.surg.2009.10.012. PubMed DOI

Gessler B., Eriksson O., Angenete E. Diagnosis, treatment, and consequences of anastomotic leakage in colorectal surgery. Int. J. Color. Dis. 2017;32:549–556. doi: 10.1007/s00384-016-2744-x. PubMed DOI PMC

Vasiliu E.C.Z., Zarnescu N.O., Costea R., Neagu S. Review of Risk Factors for Anastomotic Leakage in Colorectal Surgery. Chirurgia (Buchar. Rom. 1990) 2015;110:26305194. PubMed

Iversen H., Ahlberg M., Lindqvist M., Buchli C. Changes in Clinical Practice Reduce the Rate of Anastomotic Leakage after Colorectal Resections. World J. Surg. 2018;42:2234–2241. doi: 10.1007/s00268-017-4423-7. PubMed DOI PMC

Kasi P.M., Shahjehan F., Cochuyt J.J., Li Z., Colibaseanu D.T., Merchea A. Rising Proportion of Young Individuals with Rectal and Colon Cancer. Clin. Color. Cancer. 2019;18:e87–e95. doi: 10.1016/j.clcc.2018.10.002. PubMed DOI

Tsai Y.-Y., Chen W.T.-L. Management of anastomotic leakage after rectal surgery: A review article. J. Gastrointest. Oncol. 2019;10:1229–1237. doi: 10.21037/jgo.2019.07.07. PubMed DOI PMC

Fukada M., Matsuhashi N., Takahashi T., Imai H., Tanaka Y., Yamaguchi K., Yoshida K. Risk and early predictive factors of anastomotic leakage in laparoscopic low anterior resection for rectal cancer. World J. Surg. Oncol. 2019;17:1–10. doi: 10.1186/s12957-019-1716-3. PubMed DOI PMC

Räsänen M., Renkonen-Sinisalo L., Carpelan-Holmström M., Lepistö A. Low anterior resection combined with a covering stoma in the treatment of rectal cancer reduces the risk of permanent anastomotic failure. Int. J. Color. Dis. 2015;30:1323–1328. doi: 10.1007/s00384-015-2291-x. PubMed DOI

Van Rooijen S., Huisman D., Stuijvenberg M., Stens J., Roumen R., Daams F., Slooter G. Intraoperative modifiable risk factors of colorectal anastomotic leakage: Why surgeons and anesthesiologists should act together. Int. J. Surg. 2016;36:183–200. doi: 10.1016/j.ijsu.2016.09.098. PubMed DOI

Sciuto A., Merola G., De Palma G.D., Sodo M., Pirozzi F., Bracale U. Predictive factors for anastomotic leakage after laparoscopic colorectal surgery. World J. Gastroenterol. 2018;24:2247–2260. doi: 10.3748/wjg.v24.i21.2247. PubMed DOI PMC

Kawada K., Sakai Y. Preoperative, intraoperative and postoperative risk factors for anastomotic leakage after laparoscopic low anterior resection with double stapling technique anastomosis. World J. Gastroenterol. 2016;22:5718–5727. doi: 10.3748/wjg.v22.i25.5718. PubMed DOI PMC

La Regina D., Di Giuseppe M., Lucchelli M., Saporito A., Boni L., Efthymiou C., Cafarotti S., Marengo M., Mongelli F. Financial Impact of Anastomotic Leakage in Colorectal Surgery. J. Gastrointest. Surg. 2018;23:580–586. doi: 10.1007/s11605-018-3954-z. PubMed DOI

Lee S.W., Gregory D., Cool C.L. Clinical and economic burden of colorectal and bariatric anastomotic leaks. Surg. Endosc. 2020;34:1–8. doi: 10.1007/s00464-019-07210-1. PubMed DOI

Ha G.W., Lee M.R., Kim J.H. Adhesive small bowel obstruction after laparoscopic and open colorectal surgery: A systematic review and meta-analysis. Am. J. Surg. 2016;212:527–536. doi: 10.1016/j.amjsurg.2016.02.019. PubMed DOI

Trotter J., Onos L., McNaught C., Peter M., Gatt M., Maude K., MacFie J. The use of a novel adhesive tissue patch as an aid to anastomotic healing. Ann. R. Coll. Surg. Engl. 2018;100:230–234. doi: 10.1308/rcsann.2018.0003. PubMed DOI PMC

Testini M., Gurrado A., Portincasa P., Scacco S., Marzullo A., Piccinni G., Lissidini G., Greco L., De Salvia M.A., Bonfrate L., et al. Bovine Pericardium Patch Wrapping Intestinal Anastomosis Improves Healing Process and Prevents Leakage in a Pig Model. PLoS ONE. 2014;9:e86627. doi: 10.1371/journal.pone.0086627. PubMed DOI PMC

Yaita A., Nakamura T., Sugimachi K., Inokuchi K. Use of free peritoneal patch in reenforcing alimentary tract anastomosis. Surg. Today. 1975;5:56–63. doi: 10.1007/BF02469470. PubMed DOI

Zhong W., Xing M.M., Maibach H.I. Nanofibrous materials for wound care. Cutan. Ocul. Toxicol. 2010;29:143–152. doi: 10.3109/15569527.2010.489307. PubMed DOI

Fu X., Gao W., Fu X., Shi M., Xie W., Zhang W., Zhao F., Chen X. Enhanced wound healing in diabetic rats by nanofibrous scaffolds mimicking the basketweave pattern of collagen fibrils in native skin. Biomater. Sci. 2018;6:340–349. doi: 10.1039/c7bm00545h. PubMed DOI

Adeli H., Khorasani M.T., Parvazinia M. Wound dressing based on electrospun PVA/chitosan/starch nanofibrous mats: Fabrication, antibacterial and cytocompatibility evaluation and in vitro healing assay. Int. J. Biol. Macromol. 2019;122:238–254. doi: 10.1016/j.ijbiomac.2018.10.115. PubMed DOI

Gunatillake P.A. Biodegradable synthetic polymers for tissue engineering. Eur. Cells Mater. 2003;5:1–16. doi: 10.22203/eCM.v005a01. PubMed DOI

Luo L., He Y., Chang Q., Xie G., Zhan W., Wang X., Zhou T., Xing M., Lu F. Polycaprolactone nanofibrous mesh reduces foreign body reaction and induces adipose flap expansion in tissue engineering chamber. Int. J. Nanomed. 2016;11:6471–6483. doi: 10.2147/IJN.S114295. PubMed DOI PMC

Townsend J.M., Ott L.M., Salash J.R., Fung K.-M., Easley J.T., Seim H.B., Johnson J.K., Weatherly R.A., Detamore M.S. Reinforced Electrospun Polycaprolactone Nanofibers for Tracheal Repair in an In Vivo Ovine Model. Tissue Eng. Part A. 2018;24:1301–1308. doi: 10.1089/ten.tea.2017.0437. PubMed DOI PMC

Fuchs J., Mueller M., Daxböck C., Stückler M., Lang I., Leitinger G., Bock E., El-Heliebi A., Moser G., Glasmacher B., et al. Histological processing of un-/cellularized thermosensitive electrospun scaffolds. Histochem. Cell Biol. 2018;151:343–356. doi: 10.1007/s00418-018-1757-7. PubMed DOI PMC

Vasita R., Katti D.S. Nanofibers and their applications in tissue engineering. Int. J. Nanomed. 2006;1:15–30. doi: 10.2147/nano.2006.1.1.15. PubMed DOI PMC

Rosendorf J., Horakova J., Klicova M., Palek R., Cervenkova L., Kural T., Hošek P., Kriz T., Tegl V., Moulisova V., et al. Experimental fortification of intestinal anastomoses with nanofibrous materials in a large animal model. Sci. Rep. 2020;10:1–12. doi: 10.1038/s41598-020-58113-4. PubMed DOI PMC

Horakova J., Klicova M., Erben J., Klapstova A., Novotny V., Behalek L., Chvojka J. Impact of Various Sterilization and Disinfection Techniques on Electrospun Poly-ε-caprolactone. ACS Omega. 2020;5:8885–8892. doi: 10.1021/acsomega.0c00503. PubMed DOI PMC

Childs D.R., Murthy A.S. Overview of Wound Healing and Management. Surg. Clin. N. Am. 2017;97:189–207. doi: 10.1016/j.suc.2016.08.013. PubMed DOI

Mehrotra R., Devuyst O., Davies S.J., Johnson D.W. The Current State of Peritoneal Dialysis. J. Am. Soc. Nephrol. 2016;27:3238–3252. doi: 10.1681/ASN.2016010112. PubMed DOI PMC

Giffin D.M., Gow K.W., Warriner C.B., Walley K.R., Phang P.T. Oxygen uptake during peritoneal ventilation in a porcine model of hypoxemia. Crit. Care Med. 1998;26:1564–1568. doi: 10.1097/00003246-199809000-00025. PubMed DOI

Cai E.Z., Teo E.Y., Jing L., Koh Y.P., Qian T.S., Wen F., Lee J.W.K., Hing E.C.H., Yap Y.L., Lee H., et al. Bio-Conjugated Polycaprolactone Membranes: A Novel Wound Dressing. Arch. Plast. Surg. 2014;41:638–646. doi: 10.5999/aps.2014.41.6.638. PubMed DOI PMC

Hashemi H., Asgari S., Shahhoseini S., Mahbod M., Atyabi F., Bakhshandeh H., Beheshtnejad A.H. Application of polycaprolactone nanofibers as patch graft in ophthalmology. Indian J. Ophthalmol. 2018;66:225–228. PubMed PMC

García-Salinas S., Evangelopoulos M., Gámez-Herrera E., Arruebo M., Irusta S., Taraballi F., Mendoza G., Tasciotti E. Electrospun anti-inflammatory patch loaded with essential oils for wound healing. Int. J. Pharm. 2020;577:119067. doi: 10.1016/j.ijpharm.2020.119067. PubMed DOI

Ricciardi R., Roberts P.L., Marcello P.W., Hall J.F., Read T.E., Schoetz D.J. Anastomotic Leak Testing After Colorectal Resection. Arch. Surg. 2009;144:407–411. doi: 10.1001/archsurg.2009.43. PubMed DOI

Bsc C.L.S., Van Groningen J.T., Lingsma H., Wouters M.W., Menon A.G., Kleinrensink G.-J., Jeekel J., Lange J.F. Different Risk Factors for Early and Late Colorectal Anastomotic Leakage in a Nationwide Audit. Dis. Colon Rectum. 2018;61:1258–1266. doi: 10.1097/dcr.0000000000001202. PubMed DOI

Marchant-Forde J.N., Herskin M.S. Advances in Pig Welfare. Elsevier; Amsterdam, The Netherlands: 2018. Pigs as laboratory animals; pp. 445–475.

Bertocchi E., Barugola G., Benini M., Bocus P., Rossini R., Ceccaroni M., Ruffo G. Colorectal Anastomotic Stenosis: Lessons Learned after 1643 Colorectal Resections for Deep Infiltrating Endometriosis. J. Minim. Invasive Gynecol. 2019;26:100–104. doi: 10.1016/j.jmig.2018.03.033. PubMed DOI

Ergul E., Korukluoglu B. Peritoneal adhesions: Facing the enemy. Int. J. Surg. 2008;6:253–260. doi: 10.1016/j.ijsu.2007.05.010. PubMed DOI

Braun K.M., Diamond M.P. The biology of adhesion formation in the peritoneal cavity. Semin. Pediatr. Surg. 2014;23:336–343. doi: 10.1053/j.sempedsurg.2014.06.004. PubMed DOI

Williams D.L., Browder I.W. Murine Models of Intestinal Anastomoses. In: Di Pietro L.A., Burns A.L., editors. Wound Healing: Methods and Protocols. 1st ed. Humana Press Inc.; Totowa, NJ, USA: 2010. pp. 133–140. PubMed

Shogan B.D., Belogortseva N., Luong P.M., Zaborin A., Lax S., Bethel C., Ward M., Muldoon J.P., Singer M., Alexander Z., et al. Collagen degradation and MMP9 activation byEnterococcus faecaliscontribute to intestinal anastomotic leak. Sci. Transl. Med. 2015;7:286ra68. doi: 10.1126/scitranslmed.3010658. PubMed DOI PMC

Krarup P., Eld M., Jorgensen L., Hansen M.B., Ågren M.S. Selective matrix metalloproteinase inhibition increases breaking strength and reduces anastomotic leakage in experimentally obstructed colon. Int. J. Color. Dis. 2017;32:1277–1284. doi: 10.1007/s00384-017-2857-x. PubMed DOI

Guyton K.L., Levine Z.C., Lowry A.C., Lambert L., Gribovskaja-Rupp I., Hyman N., Zaborina O., Alverdy J.C. Identification of Collagenolytic Bacteria in Human Samples. Dis. Colon Rectum. 2019;62:972–979. doi: 10.1097/DCR.0000000000001417. PubMed DOI PMC

Li Y., Xia X., Zou Q., Ma J., Jin S., Li J., Zuo Y., Li Y. The long-term behaviors and differences in bone reconstruction of three polymer-based scaffolds with different degradability. J. Mater. Chem. B. 2019;7:7690–7703. doi: 10.1039/c9tb02072a. PubMed DOI

Ranjbar-Mohammadi M., Bahrami S.H. Electrospun curcumin loaded poly(ε-caprolactone)/gum tragacanth nanofibers for biomedical application. Int. J. Biol. Macromol. 2016;84:448–456. doi: 10.1016/j.ijbiomac.2015.12.024. PubMed DOI

Wirth U., Rogers S., Haubensak K., Schopf S., Von Ahnen T., Schardey H.M. Local antibiotic decontamination to prevent anastomotic leakage short-term outcome in rectal cancer surgery. Int. J. Color. Dis. 2017;33:53–60. doi: 10.1007/s00384-017-2933-2. PubMed DOI

Oh J., Kuan K.G., Tiong L.U., Trochsler M., Jay G., Schmidt T.A., Barnett H., Maddern G.J. Recombinant human lubricin for prevention of postoperative intra-abdominal adhesions in a rat model. J. Surg. Res. 2017;208:20–25. doi: 10.1016/j.jss.2016.08.092. PubMed DOI

Hirai K., Tabata Y., Hasegawa S., Sakai Y. Enhanced intestinal anastomotic healing with gelatin hydrogel incorporating basic fibroblast growth factor. J. Tissue Eng. Regen. Med. 2016;10:E433–E442. doi: 10.1002/term.1835. PubMed DOI

Landes L.C., Drescher D., Tagkalos E., Grimminger P., Thieme R., Jansen-Winkeln B., Lang H., Gockel I. Upregulation of VEGFR1 in a rat model of esophagogastric anastomotic healing. Acta Chir. Belg. 2017;118:161–166. doi: 10.1080/00015458.2017.1394673. PubMed DOI

Large-Scale Development of Antibacterial Scaffolds: Gentamicin Sulfate-Loaded Biodegradable Nanofibers for Gastrointestinal Applications

Antiadhesive Nanofibrous Materials for Medicine: Preventing Undesirable Tissue Adhesions

Intestinal Anastomotic Healing: What do We Know About Processes Behind Anastomotic Complications