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ORIGINAL RESEARCH article

Front. Bioeng. Biotechnol.
Sec. Biomaterials
Volume 12 - 2024 | doi: 10.3389/fbioe.2024.1506433
This article is part of the Research Topic Translational development of tailored implants based on new processing approaches and surface modifications for tissue regeneration View all articles

The influence of different crosslinking agents onto the physical properties, integration behavior and immune response of collagenbased barrier membranes

Provisionally accepted
Yanru Ren Yanru Ren 1Said Alkildani Said Alkildani 2Kim Burckhardt Kim Burckhardt 1,2Alexander Köwitsch Alexander Köwitsch 3Sanja Stojanovic Sanja Stojanovic 4,5Stevo J. Najman Stevo J. Najman 4,5Luo Liu Luo Liu 6Mike Barbeck Mike Barbeck 1*
  • 1 Department of Dermatology and Venerology, University Medical Center Rostock, Rostock, Germany
  • 2 BerlinAnalytix GmbH, Berlin, Baden-Württemberg, Germany
  • 3 Biotrics bioimplants AG, Berlin, Baden-Württemberg, Germany
  • 4 Department for Cell and Tissue Engineering, Faculty of Medicine, University of Niš, Niš, Serbia
  • 5 Department of Biology and Human Genetics, Faculty of Medicine, Nis, Serbia
  • 6 Beijing Advanced Innovation Center for Soft Matter Science and Engineering, College of Life Science and Technology, Beijing University of Chemical Technology, Beijing, Beijing Municipality, China

The final, formatted version of the article will be published soon.

    This study investigates the mechanical properties as well as in vitro and in vivo cyto-and biocompatibility of collagen membranes cross-linked with glutaraldehyde (GA), proanthocyanidins (PC), hexamethylendiisocyanate (HMDI) and 1-Ethyl-3-(3-dimethylaminopropyl)carbodiimide/Nhydroxysuccinimide (EC/NHS). A non-crosslinked membrane was used as reference control (RF). The initial in vitro cytotoxic analyses revealed that the PC, EC, and HMDI crosslinked membranes were cytocompatible, while the GA crosslinked membrane was cytotoxic and thus selected as positive control in the further in vivo study. Cross-linking enhances the tensile strength and collagenase resistance, effectively prolonging the membrane's standing time in vivo. Using (immune-) histochemistry and histomorphometrical analyses, the cellular inflammatory responses, tissue integration and vascularization patterns at 10-, 30-, and 90-days post-implantation in a subcutaneous implantation model in rats were analyzed. The PC membrane elicited the mildest inflammatory cell levels, akin to the RF membrane, while other groups induced an M1-dominated macrophage response and numerous multinucleated giant cells throughout the study period. EC membranes maintained structural stability up to 30 days post-implantation, similar to the GA group, whereas others collapsed prematurely. Concurrent with membrane collapse, transmembrane vascularization occurred across all groups. Histopathological and histomorphometry results reveal the intricate interplay of inflammatory cell populations in vascularization. These findings offer valuable insights into the pivotal role of cross-linkers in modulating mechanical properties and tissue responses of collagen membranes.

    Keywords: Guided bone regeneration (GBR), Collagen membrane, barrier membrane, transmembraneous vascularization, Macrophages, degradation, integration

    Received: 05 Oct 2024; Accepted: 29 Nov 2024.

    Copyright: © 2024 Ren, Alkildani, Burckhardt, Köwitsch, Stojanovic, Najman, Liu and Barbeck. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

    * Correspondence: Mike Barbeck, Department of Dermatology and Venerology, University Medical Center Rostock, Rostock, Germany

    Disclaimer: All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article or claim that may be made by its manufacturer is not guaranteed or endorsed by the publisher.