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Crosslinking-Dependent Design of Hyaluronic Acid Matrices for Enhanced Bioadhesion and Cellular Response
Alina Diana Panainte1, Cătălina Anișoara Peptu2, Andreea Crețeanu1
1Faculty of Pharmacy, Grigore T. Popa University of Medicine and Pharmacy Iasi, 16 Universitatii Street, 700116 Iasi, Romania.
Pharmaceutics
|May 27, 2026
Summary
Hyaluronic acid hydrogels were created using physical or covalent crosslinking. Covalent methods offer better stability and slower drug release, while physical methods improve swelling and adhesion for biomedical applications.
Area of Science:
- Biomaterials Science
- Polymer Chemistry
- Drug Delivery Systems
Background:
- Hyaluronic acid (HA) hydrogels are increasingly utilized in biomedical fields due to their biocompatibility and adaptable characteristics.
- Developing HA hydrogels with tailored properties is crucial for advanced therapeutic applications.
Purpose of the Study:
- To compare physical (poly(vinyl alcohol) incorporation) and covalent (DCC/NHS) crosslinking strategies for hyaluronic acid hydrogel fabrication.
- To evaluate the impact of crosslinking methods on hydrogel properties and drug delivery performance using piroxicam as a model drug.
Main Methods:
- Fabrication of HA hydrogels via physical crosslinking with PVA and covalent crosslinking using DCC/NHS.
- Characterization of hydrogel morphology, swelling, adhesion, enzymatic degradation, drug release kinetics, and in vitro cytocompatibility.
- Inclusion of piroxicam (Px) as a model drug to assess drug delivery capabilities.
Main Results:
- Physically crosslinked HA-PVA hydrogels demonstrated higher swelling and adhesion.
- Covalently crosslinked hydrogels exhibited superior structural stability, reduced swelling, and enhanced resistance to enzymatic degradation.
- Drug release rates were modulated by network architecture, with denser networks showing slower release.
- All developed hydrogels were found to be cytocompatible in vitro, with drug incorporation influencing cellular responses.
Conclusions:
- Crosslinking strategies significantly impact HA hydrogel physicochemical and biological properties.
- Formulation variables are key to designing HA-based hydrogels for specific biomedical applications.
- Further research is necessary to validate performance in complex biological settings beyond simplified in vitro models.
