Benzaldehyde-terminated telechelic four-armed polyethylene glycol (PEG-BA) is synthesized and cross-linked with carboxymethyl chitosan (CMC) to form dynamic hydrogels with strong mechanical performance. The gelation temperature and time, mechanical performance, and self-healing behaviors are systematically investigated. The hydrogels have good storage modulus up to 3162.06 ± 21.06 Pa, comparable to conventional bulk hydrogels. The separated alternate hydrogel lines connect together to become an integrated hydrogel film after 5 min at room temperature without any external intervention. This is due to the dynamic equilibrium between the Schiff base linkages and the aldehyde groups of PEG-BA and amine groups on CMC backbone. The hydrogel shows excellent cytocompatibility and the cell viability is as high as 90.7 ± 6.8% after 2 d 3D encapsulation in the hydrogel. In vivo tests indicate that the hydrogels can effectively stop bleeding when the hydrogel is directly injected into a rabbit liver incision. The total blood loss is reduced from 0.65 ± 0.10 g to 0.29 ± 0.11 g, and the hemostasis time is decreased from 167 ± 21 s to 120 ± 10 s, when compared to a gauze treatment with physical compression. These self-healing hydrogels have potential to be used as a novel hemostatic material.

Novel onion-like and multi-layered tubular cellulose hydrogels were constructed, for the first time, from the cellulose solution in a 7% NaOH/12% urea aqueous solvent by changing the shape of the gel cores. In our findings, the contacting of the cellulose solution with the surface of the agarose gel rod or sphere loaded with acetic acid led to the close chain packing to form immediately a gel layer, as a result of the destruction of the cellulose inclusion complex by acid through inducing the cellulose self-aggregation. Subsequently, multi-layered cellulose hydrogels were fabricated via a multi-step interrupted gelation process. The size, layer thickness and inter-layer space of the multi-layered hydrogels could be controlled by adjusting the cellulose concentrations, the gel core diameter and the contacting time of the solid-liquid interface. The multi-layered cellulose hydrogels displayed good architectural stability and solvent resistance. Moreover, the hydrogels exhibited high compressive strength and excellent biocompatibility. L929 cells could adhere and proliferate on the surface of the layers and in interior space, showing great potential as tissue engineering scaffolds and cell culture carrier. This work opens up a new avenue for the construction of the high strength multi-layered cellulose hydrogels formed from inner to outside via a fast contact of solid-liquid interface.

A series of epichlorohydrin-cross-linked hydroxyethyl cellulose/soy protein isolate composite films (EHSF) was fabricated from hydroxyethyl cellulose (HEC) and soy protein isolate (SPI) using a process involving blending, cross-linking, solution casting, and evaporation. The films were characterized with FTIR, solid-state (13)C NMR, UV-vis spectroscopy, and mechanical testing. The results indicated that cross-linking interactions occurred in the inter- and intramolecules of HEC and SPI during the fabrication process. The EHSF films exhibited homogeneous structure and relative high light transmittance, indicating there was a certain degree of miscibility between HEC and SPI. The EHSF films exhibited a relative high mechanical strength in humid state and an adjustable water uptake ratio and moisture absorption ratio. Cytocompatibility, hemocompatibility and biodegradability were evaluated by a series of in vitro and in vivo experiments. These results showed that the EHSF films had good biocompatibility, hemocompatibility, and anticoagulant effect. Furthermore, EHSF films could be degraded in vitro and in vivo, and the degradation rate could be controlled by adjusting the SPI content. Hence, EHSF films might have a great potential for use in the biomedical field.

Polysaccharide-based injectable hydrogels have several advantages in the context of biomedical use. However, the main obstruction associated with the utilization of these hydrogels in clinical application is their poor mechanical properties. Herein, we describe in situ gelling of nanocomposite hydrogels based on quaternized cellulose (QC) and rigid rod-like cationic cellulose nanocrystals (CCNCs), which can overcome this challenge. In all cases, gelation immediately occurred with an increase of temperature, and the CCNCs were evenly distributed throughout the hydrogels. The nanocomposite hydrogels exhibited increasing orders-of-magnitude in the mechanical strength, high extension in degradation and the sustained release time, because of the strong interaction between CCNCs and QC chains mediated by the cross-linking agent (β-glycerophosphate, β-GP). The results of the in vitro toxicity and in vivo biocompatibility tests revealed that the hydrogels did not show obvious cytotoxicity and inflammatory reaction to cells and tissue. Moreover, DOX-encapsulated hydrogels were injected beside the tumors of mice bearing liver cancer xenografts to assess the potential utility as localized and sustained drug delivery depot systems for anticancer therapy. The results suggested that the QC/CCNC/β-GP nanocomposite hydrogels had great potential for application in subcutaneous and sustained delivery of anticancer drug to increase therapeutic efficacy and improve patient compliance.

High strength chitin/poly(vinyl alcohol) (PVA) composite hydrogels (RCP) were constructed by adding PVA into chitin dissolved in a NaOH/urea aqueous solution, and then by cross-linking with epichlorohydrin (ECH) and freezing-thawing process. The RCP hydrogels were characterized by field emission scanning electron microscopy, FTIR, differential scanning calorimetry, solid-state (13)C NMR, wide-angle X-ray diffraction, and compressive test. The results revealed that the repeated freezing/thawing cycles induced the bicrosslinked networks consisted of chitin and PVA crystals in the composite gels. Interestingly, a jellyfish gel-like structure occurred in the RCP75 gel with 25 wt % PVA content in which the amorphous and crystalline PVA were immobilized tightly in the chitin matrix through hydrogen bonding interaction. The freezing/thawing cycles played an important role in the formation of the layered porous PVA networks and the tight combining of PVA with the pore wall of chitin. The mechanical properties of RCP75 were much higher than the other RCP gels, and the compressive strength was 20× higher than that of pure chitin gels, as a result of broadly dispersing stress caused by the orderly multilayered networks. Furthermore, the cell culture tests indicated that the chitin/PVA composite hydrogels exhibited excellent biocompatibility and safety, showing potential applications in the field of tissue engineering.

The development of natural hydrogels with sufficient strength and self-healing capacity to accelerate skin wound healing is still challenging. Herein, a hyaluronic acid nanocomposite hydrogel was developed based on aldehyde-modified sodium hyaluronate (AHA), hydrazide-modified sodium hyaluronate (ADA), and aldehyde-modified cellulose nanocrystals (oxi-CNC). This hydrogel was formed in situ using dynamic acylhydrazone bonds via a double-barreled syringe. This hydrogel exhibited improved strength and excellent self-healing ability. Furthermore, platelet-rich plasma (PRP) can be loaded in the hyaluronic acid nanocomposite hydrogels (ADAC) via imine bonds formed between amino groups on PRP (e.g., fibrinogen) and aldehyde groups on AHA or oxi-CNC to promote skin wound healing synergistically. As expected, ADAC hydrogel could protect and release PRP sustainably. In animal experiments, ADAC@PRP hydrogel significantly promoted full-thickness skin wound healing through enhancing the formation of granulation tissue, facilitating collagen deposition, and accelerating re-epithelialization and neovascularization. This self-healing nanocomposite hydrogel with PRP loading appears to be a promising candidate for wound therapy.

Multichannel nerve guide conduits (MCNGCs) have been widely studied and exhibited outstanding nerve repair function. However, the effect of the geometric structure of MCNGCs on the nerve repair function was still not clear. Herein, we postulated that MCNGCs with different inner surface area-to-volume ratios (ISA/V) of the channels inside the nerve guide conduits (NGCs) would show different nerve repair functions. Therefore, in current work, we constructed a series of hydroxyethyl cellulose/soy protein sponge-based nerve conduit (HSSN) with low, medium, and high ISA/V from hydroxyethyl cellulose (HEC)/soy protein isolate (SPI) composite sponges, which were abbreviated as HSSN-L, HSSN-M and HSSN-H, respectively. These NGCs were applied to bridge and repair a 10 mm long sciatic nerve defect in a rat model. Finally, the influence of ISA/V on nerve repair function was evaluated by electrophysiological assessment, histological investigation, and in vivo biodegradability testing. The results of electrophysiological assessment and histological investigation showed that the regenerative nerve tissues bridged with HSSN-H and HSSN-M had higher compound muscle action potential amplitude ratio, higher percentage of positive NF200 and S100 staining, larger axon diameter, lower G-ratio, and greater myelination thickness. Furthermore, the regenerative nerve tissues bridged with HSSN-H also showed higher density of regenerated myelinated nerve fibers and more number of myelin sheath layers. On the whole, the repair efficiency of the peripheral nerve in HSSN-H and HSSN-M groups might be better than that in HSSN-L. These results indicated that higher ISA/V based on HEC/SPI composite sponge may result in greater nerve repair functions. The conclusion provided a probable guiding principle for the structural designs of NGCs in the future.

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