Thiol-ene radical coupling is increasingly used for the biofunctionalisation of biomaterials and the formation of 3D hydrogels enabling cell encapsulation. Indeed, thiol-ene chemistry presents interesting features that are particularly attractive for platforms requiring specific reactions of peptides or proteins, in particular in situ, during cell culture or encapsulation: thiol-ene coupling occurs specifically between a thiol and a non-activated alkene (unlike Michael addition); it is relatively tolerant to the presence of oxygen; it can be triggered by light. Despite such interest, little is known about the factors impacting polymer thiol-ene chemistry in situ. Here we explore some of the molecular parameters controlling photoinitiated thiol-ene coupling (with UV and visible light irradiation), with a series of alkenefunctionalised polymer backbones. 1 H NMR spectroscopy is used to quantify the efficiency of couplings, whereas photo-rheology allows correlation to gelation and mechanical properties of the resulting materials. We identify the impact of weak electrolytes in regulating coupling efficiency, presumably via thiol deprotonation and regulation of local diffusion. The conformation of associated polymer chains, regulated by the pH, is also proposed to play an important role in the modulation of both thiol-ene coupling and crosslinking efficiencies. Ultimately, suitable conditions for cell encapsulations are identified for a range of polymer backbones and their impact on cytocompatibility is investigated for cell encapsulation and tissue engineering applications. Overall our work demonstrates the importance of polymer backbone design to regulate thiol-ene coupling and in situ hydrogel formation.

A core-independent approach for the design of polymer brush-functionalised nanomaterials with a fluorescent tag for RNA delivery.

Dynamic photo-responsive synthetic hydrogels offer important advantages for biomaterials design, from the ability to cure hydrogels and encapsulate cells in situ to the light-mediated control of cell spreading and tissue formation. We report the facile and effective photo-curing and photoremodelling of disulfide-crosslinked hyaluronic acid hydrogels, based on photo-oxidation of corresponding thiol residues and their radical-mediated photo-degradation. We find that the mechanical properties of disulfide hydrogels and the extent of their photo-remodelling can be tuned by controlling the photo-oxidation and photo-degradation reactions, respectively. This enables the photo-patterning of the mechanical properties of hydrogels, but also their self-healing and photomediated healing. Finally, we demonstrate the ability to encapsulate mesenchymal stromal cells within these materials and to regulate their protrusion and spreading in 3D matrices by controlling the mechanical properties of the disulfide networks. Therefore, synthetically accessible photoconfigurable disulfide hydrogels offer interesting opportunities for the design of soft biomaterials and the regulation of cell encapsulation and matrix remodelling for tissue engineering.