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

Abstract

Access to biocompatible self-assembled gels and microgels is of great interests for a variety of biological applications from tissue engineering to drug delivery. Here, the facile synthesis of supramolecular hydrogels of norbornene (nb)-functionalised chitosan (CS-nb) via UV-triggered self-assembly in the presence of Irgacure 2959 (IRG) is reported. The in vitro stable hydrogels are injectable and showed pH-responsive swelling behaviour, while their structure and mechanical properties could be tuned by tailoring the stereochemistry of the norbornene derivative (e.g. endo-or-exo). Interestingly, unlike other nb-type hydrogels, the gels possess nanopores within their structure, which might lead to potential drug delivery applications. A gelation mechanism was proposed based on hydrophobic interactions following the combination of IRG on norbornene, as supported by 1H NMR. This self-assembly mechanism was used to access microgels of size 100-150 nm which could be further functionalised and showed no significant toxicity to human dermofibroblast cells. File list (2) download file view on ChemRxiv exo-endo-gels .pdf (1.14 MiB) download file view on ChemRxiv ESI exo-endo gels.pdf (1.17 MiB)

Thiol–Norbornene Photoclick Chemistry for Grafting Antimicrobial Peptides onto Chitosan to Create Antibacterial Biomaterials

“…Thiol–norbornene reactions have been extensively studied for biomaterial functionalization in recent years. Although the most common polymers explored so far have been cellulose, pectin, gelatin, and hyaluronic acid, a few recent reports have also used chitosan as the starting biomaterial, but not for antimicrobial peptide conjugation, to the best of our knowledge. − Considering that reaction of chitosan with carbic anhydride (CA) may allow for the introduction of norbornene onto both hydroxyl and amine groups, ,, there is an enhanced probability of obtaining a high degree of substitution (DS). Thus, herein, the hypothesis to be tested is that TNPC is an improvement over former approaches for AMP conjugation onto polysaccharides (chitosan, in this case), while providing enough norbornene groups to remain available for additional reactions.…”

Chitosan Hydrogels with Embedded Thermo- and pH-Responsive Microgels as a Potential Carrier for Controlled Release of Drugs

“…Chitosan, an extensively investigated natural biopolymer, has been employed in drug release due to its considerable swelling degree in aqueous environments. , Additionally, it has been shown to have outstanding biological characteristics, including biocompatibility, biodegradability, antifungal effect, and cell adhesion that make it a potential candidate for use in a range of biomedical applications. , Specifically, the ability of the chitosan-based hydrogel to accelerate wound concentration and healing enables it to serve as an occlusive dressing material for wound healing. , Chitosan contains active −NH 2 groups at the C-2 terminal of the d -glucosamine repeating unit, which allows the biopolymer to attach with carboxyl group-containing materials via covalent linkages (amide bonds), forming a stable composite with excellent mechanical properties and good biocompatibility. − Motivated by this unique chemical behavior along with other advantageous characteristics, we combine the chitosan with microgels to fabricate soft particle-embedded hydrogel composites for controlled release of drug. In particular, the combination of chitosan hydrogels as a supporting bulk phase and stimuli-responsive soft microgel particles as modulators offers great promise to develop a novel drug delivery platform.…”

“…Chitosan, an extensively investigated natural biopolymer, has been employed in drug release due to its considerable swelling degree in aqueous environments. 49,50 Additionally, it has been shown to have outstanding biological characteristics, including biocompatibility, biodegradability, antifungal effect, and cell adhesion that make it a potential candidate for use in a range of biomedical applications. 51,52 Specifically, the ability of the chitosan-based hydrogel to accelerate wound concentration and healing enables it to serve as an occlusive dressing material for wound healing.…”

Tunable Thiol–Ene Photo-Cross-Linked Chitosan-Based Hydrogels for Biomedical Applications

“…We previously reported the synthesis of novel biocompatible CS-based microgels obtained through thiol−ene photoclick cross-linking of CS-hydrogel precursors bearing a norbornene moiety (CS-nb, Figure 1). 26,27 This precursor, obtained in a single step by ring-opening 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 solubilizing group. In the current study, we investigate the physical properties of a series of CS-nb hydrogels using three different thiol-based cross-linkers.…”