Sulfated glyco-based hydrogels as self-healing, adhesive, and anti-inflammatory dressings for wound healing.

Hydrogels have emerged as a new type of wound dressing materials that involved in different stages of the healing processes. However, most of the existing wound dressings mainly offer a protective and moisturizing layer to prevent cross-infection, while the anti-inflammatory and anti-oxidative properties are frequently induced by extra addition of other bioactive molecules. Here, a novel type of sulfated glyco-functionalized hydrogels for wound dressing was prepared through the hybrid supramolecular co-assembly of carbohydrate segments (FG, FGS and FG3S), fluorenylmethoxycarbonyl-diphenylalanine (Fmoc-FF), and diphenylalanine-dopamine (FFD). Implanting sulfated carbohydrates can mimic the structure of glycosaminoglycans (GAGs), promoting cell proliferation and migration, along with anti-inflammatory effects. In situ polymerization of FFD introduced a secondary covalent network to the hydrogel, meanwhile, providing anti-oxidation and adhesion properties to wound surfaces. Furthermore, the dynamic supramolecular interactions within the hydrogels also confer self-healing capabilities to the wound dressing materials. In vivo experiments further demonstrated significantly accelerated healing rates with the multifunctional hydrogel FG3S-FFD, indicating high application potential.

Glycopolymer-Based Antiswelling, Conductive, and Underwater Adhesive Hydrogels for Flexible Strain Sensor Application.

With the fast development of soft electronics, underwater adhesion has become a highly desired feature for various sensing uses. Currently, most adhesive hydrogels are based on catechol-based structures, such as polydopamine, pyrogallol, and tannic acid, with very limited structural variety. Herein, a new type of glycopolymer-based underwater adhesive hydrogel has been prepared straightforwardly by random copolymerization of acrylic acid, acetyl-protected/unprotected glucose, and methacrylic anhydride in dimethyl sulfoxide (DMSO). By employing a DMSO-water solvent exchange strategy, the underwater adhesion was skillfully induced by the synergetic effects of hydrophobic aggregation and hydrogen bonding, leading to excellent adhesion behaviors on various surfaces, including pig skins, glasses, plastics, and metals, even after 5 days of storage in water. In addition, the underwater adhesive hydrogels with simple and low-cost protected/unprotected carbohydrate compositions showed good mechanical and rheological properties, together with cytocompatibility and antiswelling behavior in water, all of which are beneficial for underwater adhesions. In application as a flexible strain sensor, the adhesive hydrogel exhibited stable and reliable sensing ability for monitoring human motion in real time, suggesting great potential for intelligent equipment design.

Supramolecular self-assembly of glycosaminoglycan mimetic nanostructures for cell proliferation and 3D cell culture application.

Glycosaminoglycans (GAGs), such as heparin, heparan sulfate and chondroitin sulfate, are playing important roles in various biological processes. Due to the laborious work of organic or enzymatic total synthesis of GAGs, different approaches, including glycopolymers, dendrimers, etc., have been developed to mimic the structures and bioactivities of GAGs, but the syntheses can still be difficult. In the current study, a new format of GAG mimetic structure, supramolecularly assembled polymers, have been easily prepared by mixing fluorenylmethoxycarbonyl-diphenylalanine (Fmoc-FF) and sulfated glyco-modified fluorenylmethoxy derivatives (FGS and FG3S). The self-assembly behavior of these polymers into different structural formats of nanoparticles, nanofibers and macroscopic hydrogels upon adjusted concentrations and composite ratios have been detailed studied. The nanofibers modified with highly sulfated glycol groups (FG3S/Fmoc-FF) showed strong promotion effect for cell proliferation, which efficiency was even similar to that of natural heparin, higher than nanoparticles or non-/low-sulfated glyco-modified nanofibers. Moreover, the supramolecular polymers were further made into hydrogels that capable of 3D cell culture. This study provided a novel and efficient approach for GAG mimicking, showing great potential for tissue engineering related applications.

Dual-Responsive Core Crosslinking Glycopolymer-Drug Conjugates Nanoparticles for Precise Hepatocarcinoma Therapy.

Nanoparticles (NPs) have demonstrated a potential for hepatocarcinoma therapy. However, the effective and safe NP-mediated drug transportation is still challenging due to premature leakage and inaccurate release of the drug. Herein, we designed a series of core cross-linking galactose-based glycopolymer-drug conjugates (GPDs) NPs with both redox-responsive and pH-sensitive characteristics to target and program drug release. Glycopolymer is comprised of galactose-containing units, which gather on the surface of GPD NPs and exhibit specific recognition to hepatocarcinoma cells, which over-express the asialoglycoprotein receptor. GPD NPs are stable in a normal physiological environment and can rapidly release the drug in hepatocarcinoma cells, which are reductive and acidic, by combining disulfide bond cross-linked core, as well as boronate ester-linked hydrophilic glycopolymer chain and the hydrophobic drug.