In Situ Forming, Silanized Hyaluronic Acid Hydrogels with Fine Control Over Mechanical Properties and In Vivo Degradation for Tissue Engineering Applications
Killian Flégeau, Claire Toquet, Gildas Réthoré, Cyril d’Arros, Léa Messager, Boris Halgand, Davy Dupont, Florent Autrusseau, Julie Lesoeur, Joëlle Véziers, Pascal Bordat, Anthony Brésin, Jérôme Guicheux, Vianney Delplace, H Gautier, Pierre Weiss
Abstract
In situ forming hydrogels that can be injected into tissues in a minimally-invasive fashion are appealing as delivery vehicles for tissue engineering applications. Ideally, these hydrogels should have mechanical properties matching those of the host tissue, and a rate of degradation adapted for neo-tissue formation. Here, the development of in situ forming hyaluronic acid hydrogels based on the pH-triggered condensation of silicon alkoxide precursors into siloxanes is reported. Upon solubilization and pH adjustment, the low-viscosity precursor solutions are easily injectable through fine-gauge needles prior to in situ gelation. Tunable mechanical properties (stiffness from 1 to 40 kPa) and associated tunable degradability (from 4 days to more than 3 weeks in vivo) are obtained by varying the degree of silanization (from 4.3% to 57.7%) and molecular weight (120 and 267 kDa) of the hyaluronic acid component. Following cell encapsulation, high cell viability (> 80%) is obtained for at least 7 days. Finally, the in vivo biocompatibility of silanized hyaluronic acid gels is verified in a subcutaneous mouse model and a relationship between the inflammatory response and the crosslink density is observed. Silanized hyaluronic acid hydrogels constitute a tunable hydrogel platform for material-assisted cell therapies and tissue engineering applications.