In vitro hemo- and cytocompatibility of bacterial nanocelluose small diameter vascular grafts: Impact of fabrication and surface characteristics

PLoS One. 2020 Jun 24;15(6):e0235168. doi: 10.1371/journal.pone.0235168. eCollection 2020.

Abstract

Objective: There is an increasing need for small diameter vascular grafts with superior host hemo- and cytocompatibilities, such as low activation of platelets and leukocytes. Therefore, we aimed to investigate whether the preparation of bacterial nanocellulose grafts with different inner surfaces has an impact on in vitro host cytocompatibility.

Methods: We have synthesized five different grafts in a bioreactor, namely open interface surface (OIS), inverted (INV), partially air dried (PAD), surface formed in air contact (SAC) and standard (STD) that were characterized by a different surface roughness. The grafts (length 55 mm, inner diameter 5 mm) were attached to heparinized polyvinyl chloride tubes, loaded with human blood and rotated at 37°C for 4 hours. Then, blood was analyzed for frequencies of cellular fractions, oxidative products, soluble complement and thrombin factors. The results were compared to clinically approved grafts made of polyethylene terephthalate and expanded polytetrafluoroethylene. Additionally, blood platelets were labelled with 111Indium-oxine to visualize the distribution of adherent platelets in the loop by scintigraphy.

Results: SAC nanocellulose grafts with the lowest surface roughness exhibited superior performance with <10% leukocyte and <50% thrombocyte loss in contrast to other grafts that exhibited >65% leukocyte and >90% thrombocyte loss. Of note, SAC nanocellulose grafts showed lowest radioactivity with scintigraphy analyses, indicating reduced platelet adhesion. Although the levels of reactive oxygen species and cell free DNA did not differ significantly, the levels of thrombin-antithrombin complexes were lowest in SAC grafts. However, all nanocellulose grafts exhibited enhanced complement activation.

Conclusion: The systematic variation of the inner surfaces of BNC vascular grafts significantly improves biocompatibility. Especially, SAC grafts exhibited the lowest loss of platelets as well as leukocytes and additionally significantly diminished activation of the coagulation system. Further animal studies are needed to study in vivo biocompatibilities.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Biocompatible Materials / chemistry*
  • Blood Coagulation / drug effects
  • Blood Vessel Prosthesis Implantation / methods
  • Blood Vessel Prosthesis*
  • Cellulose / chemistry*
  • Cellulose / ultrastructure
  • Graft Occlusion, Vascular / physiopathology
  • Graft Occlusion, Vascular / prevention & control
  • Heparin / pharmacology
  • Humans
  • Materials Testing / methods
  • Microscopy, Electron, Scanning
  • Platelet Adhesiveness / physiology
  • Polyethylene Terephthalates / chemistry
  • Polysaccharides, Bacterial / chemistry*
  • Polytetrafluoroethylene / chemistry
  • Surface Properties
  • Vascular Patency / drug effects
  • Vascular Patency / physiology*

Substances

  • Biocompatible Materials
  • Polyethylene Terephthalates
  • Polysaccharides, Bacterial
  • Polytetrafluoroethylene
  • Cellulose
  • Heparin

Grants and funding

This study was funded by the Koeln Fortune Program / Faculty of Medicine, University of Cologne, Germany (grant number KF212/2016, donated to corresponding author M.W.). The URL of the funder website is: https://medfak.unikoeln.de/19728.html. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. Furthermore, this study was funded by the BBraun-foundation (grant number BBST-D-17-00019R1, donated to corresponding author M.W.). The URL of the funder website is: https://www.bbraun-stiftung.de/de.html. The creation of our grafts is based on a scientific collaboration with Professor Klemm, a former University Professor of Chemistry of the University of Jena. Within this collaboration, Professor Klemm and his team developed a technique to create tubular nanocellulose grafts on the basis of our surgical expertise and input. After retirering from his University career, Professor started the KKF company in order to offer counselling for the use of polymer technology. Therefore, the affiliation in our manuscript is named as KKF company. However, the basis of our work is a scientific collaboration. Concerning the financial aspects, the whole funding of our project is based on research funds of the Köln Fortune program and was raised by our scientific working group (M. Wacker), as stated above. Based on this, we were able to finance the creation and the modifications of our grafts (personnel and material costs). In this context, we like to state, that the KKF company did not fund any of the described work, nor did they influence our scientific research, and KKF Jena did not have any influence on study design, data collection and analysis, decision to publish, or preparation of the manuscript. Nevertheless, in order to be transparent, we decided to mention the occupational affiliation of all our authors. The specific roles of these authors are articulated in the ‘author contributions’ section. The authors declare that no competing interests exist. The BNC grafts used in this study were obtained from KKF without any restrictions regarding use and publishing of scientific results yielded with the grafts described in this study. Publishing of scientific evidence linked to the BNC grafts does not interfere with any patent held by KKF Jena.