Biointegration of soft tissue-inspired hydrogels on the chorioallantoic membrane: An experimental characterization

Soft scaffold materials for cell cultures grafted onto the chorioallantoic membrane (CAM) provide innovative solutions for creating physiologically relevant environments by mimicking the host tissue. Biocompatible hydrogels represent an ideal medium for such applications, but the relationship betwee...

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Main Authors: Manuel P. Kainz, Mathias Polz, Daniel Ziesel, Marta Nowakowska, Muammer Üçal, Sabine Kienesberger, Sophie Hasiba-Pappas, Raimund Winter, Nassim Ghaffari Tabrizi-Wizsy, Sarah Kager, Theresa Rienmüller, Julia Fuchs, Michele Terzano, Christian Baumgartner, Gerhard A. Holzapfel
Format: Article
Language:English
Published: Elsevier 2025-04-01
Series:Materials Today Bio
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Online Access:http://www.sciencedirect.com/science/article/pii/S2590006425000663
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author Manuel P. Kainz
Mathias Polz
Daniel Ziesel
Marta Nowakowska
Muammer Üçal
Sabine Kienesberger
Sophie Hasiba-Pappas
Raimund Winter
Nassim Ghaffari Tabrizi-Wizsy
Sarah Kager
Theresa Rienmüller
Julia Fuchs
Michele Terzano
Christian Baumgartner
Gerhard A. Holzapfel
author_facet Manuel P. Kainz
Mathias Polz
Daniel Ziesel
Marta Nowakowska
Muammer Üçal
Sabine Kienesberger
Sophie Hasiba-Pappas
Raimund Winter
Nassim Ghaffari Tabrizi-Wizsy
Sarah Kager
Theresa Rienmüller
Julia Fuchs
Michele Terzano
Christian Baumgartner
Gerhard A. Holzapfel
author_sort Manuel P. Kainz
collection DOAJ
description Soft scaffold materials for cell cultures grafted onto the chorioallantoic membrane (CAM) provide innovative solutions for creating physiologically relevant environments by mimicking the host tissue. Biocompatible hydrogels represent an ideal medium for such applications, but the relationship between scaffold mechanical properties and reactions at the biological interface remains poorly understood. This study examines the attachment and integration of soft hydrogels on the CAM using an accessible ex ovo system. Composite hydrogels of polyvinyl alcohol and Phytagel were fabricated by sterile freeze-thawing. CAM assays, as an alternative to traditional in vivo models, enabled the evaluation of the compatibility, attachment, and biointegration of hydrogels with three distinct compositions. The mechanomimetic properties of the hydrogels were assessed through cyclic compression–tension tests, with nominal peak stresses ranging from 0.26 to 2.82 kPa in tension and −0.33 to −2.92 kPa in compression. Mechanical attachment to the CAM was measured by pull-off tests after five days of incubation. On the first day, the interface strength was similar for all hydrogel compositions. On day 5, softer hydrogels showed the greatest increase (p=0.008), followed by intermediate hydrogels (p=0.020), while the denser hydrogels showed negligible changes (p=0.073). Histological analyses revealed cell infiltration in 100% of soft, 75% of intermediate, and 13% of dense hydrogels, suggesting that softer hydrogels integrate better into the CAM by facilitating cell migration and enhancing interface strength. Chicken embryo survival rates and cytotoxicity assays confirmed the biocompatibility of the hydrogels and supported their potential for use in soft, hydrated three-dimensional scaffolds that mimic tissue environments in dynamic biological systems.Statement of significance Current research on soft scaffold materials for cell cultures often overlooks the critical relationship between mechanical properties and biological integration of these materials with host tissues. Although hydrogels, as soft porous materials, hold promise for creating physiologically relevant environments, the mechanisms driving their attachment and biointegration, especially on the chorioallantoic membrane (CAM), remain largely unexplored. This study addresses this gap by investigating the interaction between soft hydrogels and the CAM, providing valuable insights into how material properties and microstructure influence cellular responses. Our findings emphasize the importance of understanding these dynamics to develop biocompatible scaffolds that better mimic tissue environments, advancing applications in three-dimensional cell cultures on CAM assays and other biological systems.
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spelling doaj-art-b046e75ff15f4e9bb59af9bc8c82b0122025-02-05T04:32:34ZengElsevierMaterials Today Bio2590-00642025-04-0131101508Biointegration of soft tissue-inspired hydrogels on the chorioallantoic membrane: An experimental characterizationManuel P. Kainz0Mathias Polz1Daniel Ziesel2Marta Nowakowska3Muammer Üçal4Sabine Kienesberger5Sophie Hasiba-Pappas6Raimund Winter7Nassim Ghaffari Tabrizi-Wizsy8Sarah Kager9Theresa Rienmüller10Julia Fuchs11Michele Terzano12Christian Baumgartner13Gerhard A. Holzapfel14Institute of Biomechanics, Graz University of Technology, AustriaInstitute of Health Care Engineering with European Testing Center of Medical Devices, Graz University of Technology, AustriaInstitute of Health Care Engineering with European Testing Center of Medical Devices, Graz University of Technology, Austria; Gottfried Schatz Research Center for Cell Signaling, Metabolism and Aging, Division of Medical Physics and Biophysics, Medical University of Graz, AustriaDepartment of Neurosurgery, Medical University of Graz, Austria; BioTechMed-Graz, AustriaDepartment of Neurosurgery, Medical University of Graz, Austria; BioTechMed-Graz, Austria; Department of Neurology, Medical University of Graz, AustriaBioTechMed-Graz, Austria; Institute of Molecular Biosciences, University of Graz, AustriaResearch Unit for Tissue Regeneration, Repair and Reconstruction, Division of Plastic, Aesthetic and Reconstructive Surgery, Department of Surgery, Medical University of Graz, AustriaResearch Unit for Tissue Regeneration, Repair and Reconstruction, Division of Plastic, Aesthetic and Reconstructive Surgery, Department of Surgery, Medical University of Graz, AustriaDivision of Immunology, Research Unit CAM Lab, Otto Loewi Research Center, Medical University of Graz, AustriaInstitute of Health Care Engineering with European Testing Center of Medical Devices, Graz University of Technology, Austria; Division of Immunology, Research Unit CAM Lab, Otto Loewi Research Center, Medical University of Graz, AustriaInstitute of Health Care Engineering with European Testing Center of Medical Devices, Graz University of Technology, Austria; BioTechMed-Graz, AustriaInstitute of Health Care Engineering with European Testing Center of Medical Devices, Graz University of Technology, Austria; Division of Cell Biology, Histology and Embryology, Gottfried Schatz Research Center, Medical University of Graz, AustriaInstitute of Biomechanics, Graz University of Technology, AustriaInstitute of Health Care Engineering with European Testing Center of Medical Devices, Graz University of Technology, AustriaInstitute of Biomechanics, Graz University of Technology, Austria; Department of Structural Engineering, NTNU, Trondheim, Norway; Corresponding author.Soft scaffold materials for cell cultures grafted onto the chorioallantoic membrane (CAM) provide innovative solutions for creating physiologically relevant environments by mimicking the host tissue. Biocompatible hydrogels represent an ideal medium for such applications, but the relationship between scaffold mechanical properties and reactions at the biological interface remains poorly understood. This study examines the attachment and integration of soft hydrogels on the CAM using an accessible ex ovo system. Composite hydrogels of polyvinyl alcohol and Phytagel were fabricated by sterile freeze-thawing. CAM assays, as an alternative to traditional in vivo models, enabled the evaluation of the compatibility, attachment, and biointegration of hydrogels with three distinct compositions. The mechanomimetic properties of the hydrogels were assessed through cyclic compression–tension tests, with nominal peak stresses ranging from 0.26 to 2.82 kPa in tension and −0.33 to −2.92 kPa in compression. Mechanical attachment to the CAM was measured by pull-off tests after five days of incubation. On the first day, the interface strength was similar for all hydrogel compositions. On day 5, softer hydrogels showed the greatest increase (p=0.008), followed by intermediate hydrogels (p=0.020), while the denser hydrogels showed negligible changes (p=0.073). Histological analyses revealed cell infiltration in 100% of soft, 75% of intermediate, and 13% of dense hydrogels, suggesting that softer hydrogels integrate better into the CAM by facilitating cell migration and enhancing interface strength. Chicken embryo survival rates and cytotoxicity assays confirmed the biocompatibility of the hydrogels and supported their potential for use in soft, hydrated three-dimensional scaffolds that mimic tissue environments in dynamic biological systems.Statement of significance Current research on soft scaffold materials for cell cultures often overlooks the critical relationship between mechanical properties and biological integration of these materials with host tissues. Although hydrogels, as soft porous materials, hold promise for creating physiologically relevant environments, the mechanisms driving their attachment and biointegration, especially on the chorioallantoic membrane (CAM), remain largely unexplored. This study addresses this gap by investigating the interaction between soft hydrogels and the CAM, providing valuable insights into how material properties and microstructure influence cellular responses. Our findings emphasize the importance of understanding these dynamics to develop biocompatible scaffolds that better mimic tissue environments, advancing applications in three-dimensional cell cultures on CAM assays and other biological systems.http://www.sciencedirect.com/science/article/pii/S2590006425000663Biomimetic hydrogelMechanical matchSoft tissueTissue engineeringChorioallantoic membraneCell migration
spellingShingle Manuel P. Kainz
Mathias Polz
Daniel Ziesel
Marta Nowakowska
Muammer Üçal
Sabine Kienesberger
Sophie Hasiba-Pappas
Raimund Winter
Nassim Ghaffari Tabrizi-Wizsy
Sarah Kager
Theresa Rienmüller
Julia Fuchs
Michele Terzano
Christian Baumgartner
Gerhard A. Holzapfel
Biointegration of soft tissue-inspired hydrogels on the chorioallantoic membrane: An experimental characterization
Materials Today Bio
Biomimetic hydrogel
Mechanical match
Soft tissue
Tissue engineering
Chorioallantoic membrane
Cell migration
title Biointegration of soft tissue-inspired hydrogels on the chorioallantoic membrane: An experimental characterization
title_full Biointegration of soft tissue-inspired hydrogels on the chorioallantoic membrane: An experimental characterization
title_fullStr Biointegration of soft tissue-inspired hydrogels on the chorioallantoic membrane: An experimental characterization
title_full_unstemmed Biointegration of soft tissue-inspired hydrogels on the chorioallantoic membrane: An experimental characterization
title_short Biointegration of soft tissue-inspired hydrogels on the chorioallantoic membrane: An experimental characterization
title_sort biointegration of soft tissue inspired hydrogels on the chorioallantoic membrane an experimental characterization
topic Biomimetic hydrogel
Mechanical match
Soft tissue
Tissue engineering
Chorioallantoic membrane
Cell migration
url http://www.sciencedirect.com/science/article/pii/S2590006425000663
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