Overview of the results:
A series of injectable hydrogels was developed, using a newly-discovered boronate ester-based crosslinking strategy. We successfully demonstrated that optimal hydrogels are minimally- to non-swelling, stable long term (over months), tunable in terms of composition (e.g. polymer, peptide) and mechanical properties, and cytocompatible. We further characterized their viscoelastic and self-healing properties, highlighting their ability to be injected. In parallel, a series of covalent (non-viscoelastic) hydrogels was developed as controls for our investigations. Using these tunable hydrogels, we investigated the effect of the composition (e.g. polymer, peptides) and mechanical properties of the hydrogels on the secretion of encapsulated stem cells. We showed that hyaluronic acid (HA) in association with viscoelastic properties tend to increase the secretion of immunomodulatory factors by encapsulated stem cells. The investigation of subcutaneous injections of our hydrogels confirmed that the new viscoelastic hydrogels are stable for weeks in vivo, and do not trigger marked inflammatory response. Stem cells encapsulated in an optimal HA-based hydrogel were delivered in a rabbit model of OA. Our preliminary results suggest that delivering stem cells in an HA-based viscoelastic hydrogel reduces the variability in efficacy of intra-articularly delivered stem cells for the treatment of OA.
Exploitation and dissemination:
The newly-discovered crosslinking strategy has been patented (#EP 20 162 062.2). As a tunable hydrogel platform, the new hydrogels are are now being used in the context of several collaborations. These include a project dedicated to the improved delivery of neural progenitor cells, and one dedicated to the 3D culture of retinal organoids. Two new industrial collaborations are also been developed to use these gels, for tissue engineering applications and for the investigation of in vitro cell-material interactions in the context of aging, respectively.
