Injectable and Self-Healing Nanocomposite Hydrogels with Ultrasensitive pH-Responsiveness and Tunable Mechanical Properties: Implications for Controlled Drug Delivery.

Injectable, self-healing, and pH-responsive hydrogels are great intelligent drug delivery systems for controlled and localized therapeutic release. Hydrogels that show pH-sensitive behaviors in the mildly acidic range are ideal to be used for the treatment of regions showing local acidosis like tumors, wounds and infections. In this work, we present a facile preparation of an injectable, self-healing, and supersensitive pH-responsive nanocomposite hydrogel based on Schiff base reactions between aldehyde-functionalized polymers and amine-modified silica nanoparticles. The hydrogel shows fast gelation within 10 s, injectability, and rapid self-healing capability. Moreover, the hydrogel demonstrates excellent stability under neutral physiological conditions, while a sharp gel-sol transition is observed, induced by a faintly acidic environment, which is desirable for controlled drug delivery. The pH-responsiveness of the hydrogel is ultrasensitive, where the mechanical properties, hydrolytic degradation, and drug release behaviors can alter significantly when subjected to a slight pH change of 0.2. Additionally, the hydrogel's mechanical and pH-responsive properties can be readily tuned by its composition. Its excellent biocompatibility is confirmed by cytotoxicity tests toward human dermal fibroblast cells (HDFa). The novel injectable, self-healing, and sensitive pH-responsive hydrogel serves as a promising candidate as a localized drug carrier with controlled delivery capability, triggered by acidosis, holding great promise for cancer therapy, wound healing, and infection treatment.

Concentrated sulfuric acid aqueous solution enables rapid recycling of cellulose from waste paper into antimicrobial packaging.

Waste paper is a major contributor to municipal and industrial waste, and its recycle and reuse are a current challenge. The aim of this research is to convert waste paper into value-added cellulose films through rapid dissolution in pre-cooled H2SO4 aqueous solution. Two types of waste paper, office paper and cardboard, could be dissolved within 210 s. The regenerated office paper films were transparent, and exhibited excellent mechanical properties (tensile strength: 77.55 ±â€¯6.52 MPa, elongation at break: 2.67 ±â€¯0.30 %, and Young's modulus: 5451.67 ±â€¯705.23 MPa), which were comparable to those of cellulose films prepared from spruce pulp in the same solvent. The mixed paper films showed a dramatically reduced UV transmittance due to the existence of lignin. Moreover, the regenerated films were a promising matrix to load antimicrobial compounds, and thus inhibited the growth of pathogenic bacteria. Therefore, this work provides a convenient way to directly convert waste paper into biodegradable antimicrobial packaging materials.

Stretchable, tough, self-recoverable, and cytocompatible chitosan/cellulose nanocrystals/polyacrylamide hybrid hydrogels.

As medical practitioners' interest in hydrogels continues to grow, their new expectations in terms of mechanical properties, biocompatibility and durability are changed. Here, we demonstrated a new strategy to improve both mechanical properties and self-recovery of double network (DN) hydrogels by introducing a self-healing network, consisting of carboxymethyl chitosan (CMC) and dialdehyde cellulose nanocrystals (DACNC). Notably, the hydrogel could be repeatedly stretched to 4 times its initial length and has tensile strength of 244 kPa, and completely recovered its shape when compressed by 90% and had the compressive strength up to 8 MPa. In addition, the deformed hydrogel recovered 81.3% of its dissipated energy at room temperature without any external stimuli. The hydrogel also exhibited good biocompatibility. We have developed a new method to fabricate stretchable and tough hydrogels that could spontaneously self-repair following mechanical deformation. They are promising for controlled drug release and dye adsorption.

On-Demand Dissolvable Self-Healing Hydrogel Based on Carboxymethyl Chitosan and Cellulose Nanocrystal for Deep Partial Thickness Burn Wound Healing.

Deep partial thickness burn wounds present big challenges due to the long healing time, large size and irregular shape, pain and reinjury at wound dressing changes, as well as scarring. The clinically effective therapy to alleviate pain at wound dressing changes, and the scar left on the skin after the healing of wound is still unavailable. To combat this, we develop a nanocomposite self-healing hydrogel that can be injected into irregular and deep burn wound beds and subsequently rapidly self-heal to reform into an integrated piece of hydrogel that thoroughly fills the wound area and protects the wound site from external environment, finally being painlessly removed by on-demand dissolving using amino acid solution at wound dressing changes, which accelerates deep partial thickness burn wound healing and prevents scarring. The hydrogel is made out of naturally occurring polymers, namely, water-soluble carboxymethyl chitosan (CMC) and rigid rod-like dialdehyde-modified cellulose nanocrystal (DACNC). They are cross-linked by dynamic Schiff-base linkages between amines from CMC and aldehydes from DACNC. The large aspect ratio and specific surface area of DACNC raise massive active junctions within the hydrogel, which can be readily broken and reformed, allowing hydrogel to rapidly self-heal. Moreover, DACNC serves as nanoreinforcing fillers to improve the hydrogel strength, which also restricts the "soft" CMC chains' motion when soaked in aqueous system, endowing high fluid uptake capacity (350%) to hydrogel while maintaining integrity. Cytotoxicity assay and three-dimensional cell culture demonstrate excellent biocompatibility of the hydrogel and capacity as extracellular matrix to support cell growth. This work opens a novel pathway to fabricate on-demand dissolvable self-healing hydrogels to speed deep partial thickness burn wound healing and eliminate pain at wound dressing changes and prevent scar formation.

Controllable immobilization of naringinase on electrospun cellulose acetate nanofibers and their application to juice debittering.

Electrospinning is a facile method to fabricate nanofibers, in terms of their high specific surface area and porous structure. Electrospun nanofibrous mats are excellent candidates for immobilization of enzymes. In this study, a simple route based on electrospinning and layer-by-layer (LBL) self-assembly processes has been developed to prepared naringinase/alginate multilayer coated electrospun cellulose acetate nanofibers. The content of immobilized naringinase could be tuned by adjusting the number of multilayers. XPS results indicated that naringinase was successfully immobilized on cellulose acetate nanofibers. SEM images showed the nanofibers maintain their sharp but became rougher after multilayer coating. Besides, the surface area of electrospun cellulose acetate nanofibers decreased and mesopores reduced. The major bitter components of grapefruit juice are naringin and limonin, naringin could be slightly removed by hydrolysis with naringinase and limonin might be removed by adsorption with cellulose acetate nanofibers.

Injectable Self-Healing Hydrogel with Antimicrobial and Antifouling Properties.

Microbial adhesion, biofilm formation and associated microbial infection are common challenges faced by implanted biomaterials (e.g., hydrogels) in bioengineering applications. In this work, an injectable self-healing hydrogel with antimicrobial and antifouling properties was prepared through self-assembly of an ABA triblock copolymer employing catechol functionalized polyethylene glycol (PEG) as A block and poly{[2-(methacryloyloxy)-ethyl] trimethylammonium iodide}(PMETA) as B block. This hydrogel exhibits excellent thermosensitivity, and can effectively inhibit the growth of E. coli (>99.8% killing efficiency) and prevent cell attachment. It can also heal autonomously from repeated damage, through mussel-inspired catechol-mediated hydrogen bonding and aromatic interactions, exhibiting great potential in bioengineering applications.

Fabrication of flexible self-standing all-cellulose nanofibrous composite membranes for virus removal.

All-cellulose nanocomposite membranes with excellent performance were successfully fabricated as novel filtration system to remove nanoparticles and virus from aqueous medium. These membranes were composed of two combined layers: an electrospun cellulose nanofabric layer treated by hot-pressing to provide mechanical support and a coating of regenerated cellulose gel with tiny inter-connected pores as barrier. Hot-pressing did not affect the fiber shape of electrospun nanofabrics, but significantly improved their mechanical properties due to increased hydrogen bonds. The regenerated cellulose gel formed a porous coating that tightly attached to electrospun nanofabrics, and its pore size varied depending on cellulose source, solution concentration, and drying process. By assembling these two layers together, the nanocomposite membranes showed the notable retention of negatively charged 100 nm latex beads (99.30%). Moreover, the electronegative nature of cellulose membranes imparted the rejection ratio of 100% and (98.68 ± 0.71)% against positively charged 50 nm latex beads and Hepatitis C Virus, respectively.

Strong and Rapidly Self-Healing Hydrogels: Potential Hemostatic Materials.

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.

KGM and PMAA based pH-sensitive interpenetrating polymer network hydrogel for controlled drug release.

Sequential interpenetrating polymer networks (IPN) hydrogels based on konjac glucomannan (KGM) and poly(methacrylic acid) (PMAA) were prepared by immersion of a solution of methacrylic acid (MAA) monomer with cross-linker N,N'-methylenebisacrylamide (MBAAm) and initiating into a pre-fabricated dried KGM gel. Polymerization and cross-linking of MAA inside the KGM network resulted in a novel biodegradable pH-sensitive IPN hydrogel. The studies on the swelling behavior of IPN hydrogels reveal their sensitive response to environment pH value. It was possible to modulate the degree of swelling of the IPN gels by changing the KGM/PMAA ratio and the cross-linking density of the PMAA component. The KGM component in the IPN can be degraded by ß-glycosidase Mannaway25L. In vitro drug release behavior of IPN hydrogels were investigated under different environments using model drugs 5-fluorouracil. The results suggested that such an IPN hydrogel can be exploited as carrier candidate for colon-specific drug delivery.

Antibacterial multilayer films fabricated by LBL immobilizing lysozyme and HTCC on nanofibrous mats.

Cellulose acetate nanofibrous mats were prepared by electrospunning technique. Positively charged and negatively charged composites were alternately deposited on negatively charged CA mats via layer-by-layer self-assembly technique. The morphology and inhibition rate of samples were investigated by regulating number of deposition bilayers and composition of outermost layer. Field emission scanning electron microscopy images indicated that the average diameter of fibers was increased with increasing the number of coating bilayers. Additionally, the catalytic activity of immobilized LY was measured and results showed "layer-by-layer alternative oscillation" phenomenon. The results of antibacterial assay indicated that (LY-HTCC/ALG)(10.5) films coating had the best inhibitory effect.