The in-vitro biocompatibility of ureido-pyrimidinone compounds and polymer degradation products

Paul J. Besseling, Tristan Mes, Anton W. Bosman, Joris W. Peeters, Henk M. Janssen, Maarten H. Bakker, Joost O. Fledderus, Martin Teraa, Marianne C. Verhaar, Hendrik Gremmels, Patricia Y.W. Dankers (Corresponding author)

Research output: Contribution to journalArticleAcademicpeer-review

Abstract

Supramolecular biomaterials based on ureido-pyrimidinone (UPy) moieties are versatile polymer materials as their function can be tailored to the application. These UPy-materials can be designed into polymer coatings, self-healing polymers, hydrogels and elastomers. The biocompatibility of UPy-based materials and their degradation products is a long-term success requirement for many regenerative medicine and biomedical applications. Earlier research has shown that UPy-based materials and polymers display no immediate toxic effects, but in-depth in-vitro studies on potential UPy-polymer degradation products have not been executed. Owing to their resemblance to naturally occurring purines and pyrimidines, UPy-compounds and their degradation products could potentially initiate an immune response or be mutagenic. Accordingly, 11 selected UPy-compounds were synthesized, and their effect on cell viability, wound healing, and their immunogenicity and potential mutagenic potential, were studied. We showed that low molecular weight degradation products of UPy-based biomaterials do not affect cell viability, nor do these interfere with several aspects of endothelial function including proliferation, angiogenic sprouting and cellular migration even in levels exceeding plausibly attainable concentrations. Furthermore, the compounds are neither immunogenic nor mutagenic, showing that UPy-biomaterials exhibit good biocompatibility in vitro, and could in principle be used in humans.

Original languageEnglish
Number of pages11
JournalJournal of Polymer Science
VolumeXX
Issue numberXX
DOIs
Publication statusAccepted/In press - 29 Mar 2021

Bibliographical note

Funding Information:
This work was financially supported by the European Research Council (FP7/2007‐2013) ERC Grant Agreement 308045, and the Ministry of Education, Culture and Science (Gravity program 024.001.035). Also, the InSiTeVx project is acknowledged (project number 436001003), that is financially supported by ZonMw within the LSH 2Treat program and the Nierstichting.

Publisher Copyright:
© 2021 The Authors. Journal of Polymer Science published by Wiley Periodicals LLC.

Copyright:
Copyright 2021 Elsevier B.V., All rights reserved.

Keywords

  • in-vitro biocompatibility
  • polymer degradation products
  • supramolecular biomaterials
  • ureido-pyrimidinone (UPy)

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