Nanocontroller-mediated dissolving hydrogel that can sustainably release cold-mimetic menthol to induce adipocyte browning for treating obesity and its related metabolic disorders.

Obesity leads to the development of many metabolic diseases, causing severe health problems. Menthol can induce adipocyte browning and thus has been used to combat obesity. To deliver menthol with a sustained effect, an injectable hydrogel that comprises carboxymethyl chitosan and aldehyde-functionalized alginate that are crosslinked through dynamic Schiff-base linkages is developed to load menthol-cyclodextrin inclusion complexes (IC). To render the as-developed hydrogel soluble after its payload is released, amino acid-loaded liposomes, functioning as nanocontrollers, are covalently grafted onto networks of the hydrogel. Upon subcutaneous injection in mice with diet-induced obesity, the as-developed hydrogel absorbs body fluids and spontaneously swells, expanding and stretching its networks, gradually releasing the loaded IC. Menthol then disassociates from the released IC to induce adipocyte browning, triggering fat consumption and increasing energy expenditure. Meanwhile, the expanded hydrogel networks destabilize the grafted liposomes, which function as built-in nanocontrollers, unleashing their loaded amino acid molecules to disrupt the dynamic Schiff-base linkages, causing hydrogel to dissolve. The thus-developed nanocontroller-mediated dissolving hydrogel realizes the sustained release of menthol for treating obesity and its related metabolic disorders without leaving exogenous hydrogel materials inside the body, and thereby preventing any undesired adverse effects.

A Biodegradable Chitosan-Polyurethane Cryogel with Switchable Shape Memory.

Cryogels are matrices that are formed in moderately frozen solutions of monomeric or polymeric precursors. They have the advantages of interconnected macropores, structural stability, and compressibility. Meanwhile, thermally induced shape memory is an attractive feature of certain functional materials. Although there have been several studies concerning shape-memory cryogels, little work has been conducted on shape-memory cryogels with biodegradability. In this study, a water-based biodegradable difunctional polyurethane with a shape-memory property was synthesized and used as the nanoparticulate crosslinker to react with chitosan to form a shape-memory cryogel. The thermally induced shape-memory mechanism was clarified using in situ wide-angle X-ray scattering (WAXS) and small-angle X-ray scattering (SAXS) during the shape-memory process. The in situ WAXS showed the changes of crystallinity in the crosslinker and the cryogel during the shape fixation and recovery processes. The in situ SAXS revealed the orientation of crystallinity of the crosslinker and the cryogel as the mechanism for shape memory. The strip-shape cryogel was deformed at 50 °C to U-shape and fixed at - 20 °C, which was squeezable at 25 °C and returned to the strip-shape at 50 °C in air. The shape recovery was further tested in water at two different temperatures. The injected cryogel recovered the U-shape in 4 °C water, representing elastic recovery, and transformed to a long strip in 37 °C water, representing the switchable shape memory. Moreover, the shape-memory cryogel sheet with a large dimension (10 mm × 10 mm × 1.1 mm cryogel sheet) or with complex structures (N, T, and U shapes) could be fixed as a rod, injected through a 16 G needle, and return to its original shape in 37 °C water, all of which could not be achieved by the conventional cryogel. Human mesenchymal stem cells grown in the shape-memory cryogel scaffolds displayed long-term proliferation and chondrogenic potential. Their unique injectability and cytocompatibility suggested potential applications of shape-memory cryogels as injectable and expandable templates for tissue engineering and minimally invasive surgery.

Thermoresponsive and Conductive Chitosan-Polyurethane Biocompatible Thin Films with Potential Coating Application.

Conductive thin films have great potential for application in the biomedical field. Herein, we designed thermoresponsive and conductive thin films with hydrophilicity, strain sensing, and biocompatibility. The crosslinked dense thin films were synthesized and prepared through a Schiff base reaction and ionic interaction from dialdehyde polyurethane, N-carboxyethyl chitosan, and double-bonded chitosan grafted polypyrrole. The thin films were air-dried under room temperature. These thin films showed hydrophilicity and conductivity (above 2.50 mS/cm) as well as responsiveness to the deformation. The tensile break strength (9.72 MPa to 15.07 MPa) and tensile elongation (5.76% to 12.77%) of conductive thin films were enhanced by heating them from 25 °C to 50 °C. In addition, neural stem cells cultured on the conductive thin films showed cell clustering, proliferation, and differentiation. The application of the materials as a conductive surface coating was verified by different coating strategies. The conductive thin films are potential candidates for surface modification and biocompatible polymer coating.