Facile Synthesis of Chitosan-Based Hydrogels and Microgels through Thiol–Ene Photoclick Cross-Linking

Abstract

Polysaccharide-based microgels are effective vectors for biopharmaceutics delivery and functional components in tissue engineering due to their bioactivity and biocompatibility. Currently, the synthesis of chemically crosslinked microgels typically requires long reaction times, high energy input and are low yielding due to low volumes of water phase used. Herein, we report the synthesis of norbornene-derivatized chitosan (CS-nbn-COOH), which can undergo rapid gelation in the presence of a thiolated crosslinker through the highly efficient thiol-ene photoclick reaction. This water-soluble photocrosslinkable derivative, synthesized on scale via a single step

Reactive Precursor Particles as Synthetic Platform for the Generation of Functional Nanoparticles, Nanogels, and Microgels

“…For example, norbornene‐derived chitosan microgels, prepared in a water‐in‐oil templating method, were crosslinked in the presence of a thiolated crosslinker. Residual norbornene groups of the microgels were used for further postparticle formation modification through tetrazine ligation, which was demonstrated by grafting a self‐quenching fluorescent tetrazine probe to the microgels …”

Norbornene-Functionalized Chitosan Hydrogels and Microgels via Unprecedented Photoinitiated Self-Assembly for Potential Biomedical Applications

“…Tet-Coum was synthesized as previously reported. 32 Other reagents were purchased from Sigma, Acros, Fluka or Lancaster and used as received. Dialysis against dionised (DI) water (MilliQ; resistivity 18.2 MW cm and total organic content (TOC) < 4 ppb) were performed using a SnakeSkin dialysing tubing with a molecular weight cut-off (MWCO) of 10 kDa (Thermo Scientific).…”

“…CS-nb derivatives were synthesized as previously described. 32 Briefly, CS (1 g, 5.9 mmol) was dissolved in 100 mL of 2% acetic acid (AcOH) in DI water. Once solubilised, the desired carbic anhydride (CA-endo, CA-exo or CA-h, 5.9 mmol) was added, and the mixture was stirred at 50 °C for 2 days.…”

Tuneable Thiol-Ene Photo-Crosslinked Chitosan-Based Hydrogels for Biomedical Applications

“…We previously reported the synthesis of novel biocompatible CS-based microgels obtained through thiol-ene photockick crosslinking of CS-hydrogel precursors bearing a norbornene moiety (CS-nb, Figure 1). 21,22 This precursor, obtained in a single step by ringopening of cheap and commercially available carbic anhydride, presented improved water solubility compared to native CS, which was attributed to the concomitant introduction of a carboxylate moiety acting as a solubilising group. In this current study, we investigate the physical properties of a series of CS-nb hydrogels using different thiol-based crosslinkers.…”

“…For a minimum CS concentration of 1 w:v%, hydrogels employing CS-nb as the starting material were generated within seconds in all cases under UV-A, with Irgacure (IRG) as photoinitiator 21 and three different cross-linkers: a short and a long thiolated PEG derivative (namely HS-PEG2-SH and HS-PEG40-SH with respect to the number of ethylene glycol repeat units), and a thiolated CS (CS-SH), synthesized by ring-opening of Traut's reagent 23 , respectively (see Figure 1 for chemical structures). It was proposed that the final properties of CS-nb hydrogels would be influenced by the nature of the crosslinker structure.…”