<div class="csl-bib-body">
<div class="csl-entry">Baltzaki, M. C. I., Bushi, J., Fernández-Pérez, J., & Baudis, S. (2025, May 22). <i>PVA-based hydrogels for skin regeneration: Using MMP-Sensitive crosslinkers for cellular remodelling</i> [Conference Presentation]. Tissue Engineering and Regenerative Medicine Society (TERMIS) European Congress 2025, Freiburg, Germany. http://hdl.handle.net/20.500.12708/224982</div>
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dc.identifier.uri
http://hdl.handle.net/20.500.12708/224982
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dc.description.abstract
Introduction/Objectives
This study aims to develop a tissue-responsive hydrogel scaffold to support skin tissue regeneration by
comparing different crosslinkers, including a matrix-metalloproteinase (MMP)-sensitive crosslinker
which facilitates cell-matrix remodeling. The different materials produced were characterized in an
acellular and cellular context, aiming to enhance cell viability and proliferation in tissue regeneration
applications.
Methods
Norbornene-functionalized polyvinyl alcohol (PVA-NB) was used as the hydrogel precursor and was
rapidly crosslinked under UV-light (<60 s) with cell-cleavable and non-cleavable crosslinkers, such as
an MMP sequence flanked by two cysteines, and a dithiolated Polyethylene glycol (HS-PEG-SH),
respectively, in presence of 0.1 wt% of Lithium phenyl-2,4,6-trimethylbenzoylphosphinate (LAP). The
final formulation concentration of PVA-NB was 5 wt%, and 50% of the norbornene groups were used for
the crosslinking. A thiolated cell-adhesion promoting peptide sequence including the
Arginine-Glycine-Aspartic Acid (RGD) motif was also incorporated in the hydrogels. The produced
matrices were characterized in terms of swelling, long-term stability, degradation kinetics and
photorheology. After all conditions were studied and optimized, fibroblasts were encapsulated within the
matrix and the viability, adhesion and cell-matrix interactions were evaluated.
Results
A dithiolated PEG with a similar molecular weight to the MMP was used to better understand and
compare the effects inflicted upon the material by the different crosslinkers. The two different hydrogels
exhibited similar photorheological behavior, such as reactivity and storage modulus of approximately
2 kPa. Their swelling behavior was also very similar as well as their stability over time under
physiological conditions, where the hydrogels were not dissolved after 45 days. However, a different
trend was observed after investigation of their accelerated enzymatic degradation kinetics using
collagenase. In fact, the PVA-MMP hydrogels had degraded within 24 hours whereas the non-cleavable
PVA-PEG hydrogels were only 20% degraded after 5 days. Immortalized adult dermal fibroblasts were
mixed in the formulation to enable observation of the cell-matrix interactions. The viability remained high
after 14 days, proving that the matrices exhibit high biocompatibility. Further microscopy observation
after 2 weeks in culture revealed that the cells had longer protrusions and a diversity of morphologies in
the PVA-MMP hydrogel, whereas cells remained rounded when encapsulated in the PVA-PEG
hydrogels, despite the presence of RGD in both formulations.
Conclusions
The cell-responsive hydrogel platform developed in this study provides a dynamic environment for tissue
regeneration. This cleavable design is well-suited for clinical applications, as it provides mechanical
integrity and the capacity for cellular remodeling. Furthermore, the material’s adaptability to numerous
formats, including electrospinning, granular hydrogels, light-based high-resolution techniques
(Two-photon polymerization or volumetric printing) and injectable hydrogels expands its potential utility
in future regenerative therapies.
Acknowledgements
Christian Doppler Research Association, Austrian Federal Ministry for Digital & Economic Affairs,
National foundation for Research, Technology & Development.
Disclosure of interest: None declared
en
dc.description.sponsorship
Christian Doppler Forschungsgesells
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dc.language.iso
en
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dc.subject
Hydrogels
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dc.subject
skin regeneration
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dc.subject
tissue regeneration
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dc.title
PVA-based hydrogels for skin regeneration: Using MMP-Sensitive crosslinkers for cellular remodelling
en
dc.type
Presentation
en
dc.type
Vortrag
de
dc.contributor.affiliation
TU Wien, Austria
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dc.relation.grantno
CDL Baudis
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dc.type.category
Conference Presentation
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tuw.project.title
Christian Doppler Labor für Fortschrittliche Polymere für Biomaterialien und den 3D Druck