1. Bioadhesive Hyaluronic Acid/Dopamine Hydrogels for Vascular Applications Prepared by Initiator-Free Crosslinking
- Author
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Tamara Melnik, Senda Ben Ameur, Nasreddine Kanfar, Laurent Vinet, Florence Delie, and Olivier Jordan
- Subjects
hydrogel ,hyaluronic acid ,bioadhesion ,mussel inspired polymers ,initiator-free crosslinking ,perivascular administration ,Biology (General) ,QH301-705.5 ,Chemistry ,QD1-999 - Abstract
Intimal hyperplasia, a vascular pathology characterized by vessel wall thickening, is implicated in vein graft failures. For efficient prevention, a biodegradable drug delivery system should be applied externally to the graft for an extended time. Finding a gel suitable for such a system is challenging. We have synthesized HA-Dopamine conjugates (HA-Dop) with several degrees of substitution (DS) and used two crosslinking methods: initiator-free crosslinking by basic pH shift or commonly used crosslinking by a strong oxidizer, sodium periodate. The rheological properties, bioadhesion to vascular tissue, cytocompatibility with fibroblasts have been compared for both methods. Our results suggest that initiator-free crosslinking provides HA-Dop gels with more adequate properties with regards to vascular application than crosslinking by strong oxidizer. We have also established the cytocompatibility of the initiator-free crosslinked HA-Dop gels and the cytotoxicity of dopamine-sodium periodate combinations. Furthermore, we have incorporated a drug with anti-restenotic effect in perivascular application, atorvastatin, into the gel, which showed adequate release profile for intimal hyperplasia prevention. The oxidizer-free formulation with improved bioadhesion holds promise as an efficient and safe drug delivery system for vascular applications.
- Published
- 2022
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