All-in-one polysaccharide hydrogel with resistant vascular burst pressure and cooperative wound microenvironment regulation for fatal arterial hemorrhage and diabetic wound healing.

Fatal massive hemorrhage and diabetic wound healing are world widely challenging in surgical managements, and uncontrolled bleeding, chronic inflammation and damaged remodeling heavily hinder the whole healing processes. Considering hemostasis, inflammation and wound microenvironment cooperatively affect the healing progression, we design all-in-one beta-glucan (BG) hybrid hydrogels reinforced with laponite nanoclay that demonstrate tunable tissue adhesion, resistant vascular burst pressure and cooperative wound microenvironment regulation for arterial hemostasis and diabetic wound prohealing. Those hydrogels had honeycomb-like porous microstructure with average pore size of 7-19 µm, tissue adhesion strength of 18-46 kPa, and vascular burst pressure of 58-174 mmHg to achieve superior hemostasis in rat liver and femoral artery models. They could effectively scavenge reactive oxygen species, transform macrophages from proinflammatory M1 into prohealing M2, and shorten the inflammation duration via synergistic actions of BG and nitric oxide (NO). Single treatment of NO-releasing BG hybrid hydrogels attained complete closure of diabetic wounds within 14 days, orchestrated to accelerate the epithelization and dermis growth, and restored normal vascularization, achieving high performance healing with optimal collagen deposition and hair follicle regeneration. Consequently, this work opens up a new avenue to design all-in-one polysaccharide hydrogels for applications in massive bleeding hemostats and diabetic wound dressings.

The H2O2 Self-Sufficient 3D Printed ß-TCP Scaffolds with Synergistic Anti-Tumor Effect and Reinforced Osseointegration.

Tumor recurrence and massive bone defects are two critical challenges for postoperative treatment of oral and maxillofacial tumor, posing serious threats to the health of patients. Herein, in order to eliminate residual tumor cells and promote osteogenesis simultaneously, the hydrogen peroxide (H2O2) self-sufficient TCP-PDA-CaO2-CeO2 (TPCC) scaffolds are designed by preparing CaO2 or/and CeO2 nanoparticles (NPs)/chitosan solution and modifying the NPs into polydopamine (PDA)-modified 3D printed TCP scaffolds by rotary coating method. CaO2 NPs loaded on the scaffolds can release Ca2+ and sufficient H2O2 in the acidic tumor microenvironment (TME). The generated H2O2 can further produce hydroxyl radicals (·OH) under catalysis effect by peroxidase (POD) activity of CeO2 NPs, in which the photothermal effect of the PDA coating enhances its POD catalytic effect. Overall, NPs loaded on the scaffold chemically achieve a cascade reaction of H2O2 self-sufficiency and ·OH production, while functionally achieving synergistic effects on anti-tumor and bone promotion. In vitro and in vivo studies show that the scaffolds exhibit effective osteo-inductivity, induced osteoblast differentiation and promote osseointegration. Therefore, the multifunctional composite scaffolds not only validate the concept of chemo-dynamic therapy (CDT) cascade therapy, but also provide a promising clinical strategy for postoperative treatment of oral and maxillofacial tumor.

Wound microenvironment regulatory poly(L-glutamic acid) composite hydrogels containing metal ion-coordinated nanoparticles for effective hemostasis and wound healing.

Regulating the wound microenvironment to promote proliferation, vascularization, and wound healing is challenging for hemostats and wound dressings. Herein, polypeptide composite hydrogels have been simply fabricated by mixing a smaller amount of metal ion-coordinated nanoparticles into dopamine-modified poly(L-glutamic acid) (PGA), which had a microporous size of 10-16 µm, photothermal conversion ability, good biocompatibility, and multiple biological activities. In vitro scratch healing of fibroblast L929 cells and the tube formation of HUVECs provide evidence that the PGA composite hydrogels could promote cell proliferation, migration, and angiogenesis with the assistance of mild photothermia. Moreover, these composite hydrogels plus mild photothermia could effectively eliminate reactive oxygen species (ROS), alleviate inflammation, and polarize the pro-inflammatory M1 macrophage phenotype into the pro-healing M2 phenotype to accelerate wound healing, as assessed by means of fluorescent microscopy, flow cytometry, and quantitative real-time polymerase chain reaction (qRT-PCR). Meanwhile, a rat liver bleeding model illustrates that the composite hydrogels reduced the blood loss ratio to about 10% and shortened the hemostasis time to about 25 s better than commercial chitosan-based hemostats. Furthermore, the full-thickness rat skin defect models showcase that the composite hydrogels plus mild photothermia could proheal wounds completely with a fast healing rate, optimal neovascularization, and collagen deposition. Therefore, the biodegradable polypeptide PGA composite hydrogels are promising as potent wound hemostats and dressings.

Single-Molecule Imaging of Reactive Oxygen Species on a Semiconductor Nano-Heterostructure for Understanding Photocatalytic Heterogeneity in Aqueous.

We constructed a single-molecule fluorescence imaging technique to monitor the spatiotemporal distribution of the hydroxyl radical (•OH) on TiO2-attached multiwalled carbon nanotubes (TiO2-MWCNTs) in aqueous. We found the heterogeneous distribution of •OH is closely related to the composition and heterostructure of the catalysts. The dynamic •OH production rate was evaluated by counting the single-molecule fluorescent bursts. We further confirmed the production of •OH on TiO2-MWCNTs mainly occurred via electron reduction during the aqueous photocatalytic process. Our study reveals the mechanism of reactive oxygen species involved photocatalytic reaction and guides the design of advanced semiconductor photocatalysts.

Photoresponsive Polypeptide-Glycosylated Dendron Amphiphiles: UV-Triggered Polymersomes, OVA Release, and In Vitro Enhanced Uptake and Immune Response.

Efficient therapeuic proteins' delivery into mammalian cells and subcellular transport (e.g., fast escape from endolysosomes into cytoplasm) are two key biological barriers that need to be overcome for antigen-based immunotherapy and related biomedical applications. For those purposes, we designed a novel kind of photoresponsive polypeptide-glycosylated poly(amidoamine) (PAMAM) dendron amphiphiles (PGDAs), and their synthesis, UV-responsive self-assembly, and triggered ovalbumin (OVA) release have been fully investigated. The highly anisotropic PGDA4 with a glycosylated second-generation PAMAM dendron self-assembled into stable polypeptide vesicles (polymersomes) within 20-50 wt % water, which exhibited UV-responsive reassembly, dynamic binding with a lectin of concanavalin A, and an accelerated OVA release in vitro. Moreover, upon 365 nm UV irradiation, the self-assembled polymersomes of those glycopolypeptides were transformed into micellar aggregates in aqueous solution at pH 7.4 but disassembled completely at pH 5. The OVA-loaded polymersomes could efficiently deliver OVA into RAW264.7 cells and achieve enhanced endolysosomes escape upon UV irradiation, as revealed by flow cytometry and confocal laser scanning microscopy (CLSM). Furthermore, the enzyme-linked immunosorbent assay (ELISA) showed that the blank sugar-coated polypeptidosomes activated a high level of tumor necrosis factor α (TNF-α) of 468 pg/mL, playing a better role of immune adjuvant for activating the macrophages. Upon the UV irradiation with a dose of 3 J/cm2, the OVA-loaded polymersomes could further stimulate RAW264.7 and enhance the TNF-α level by about 45%. Consequently, this work provides a versatile platform to construct photosensitive and sugar-coated polymersomes of glycopolypeptides that have potential applications for protein delivery, immune adjuvant, and antigen-based immunotherapy.

A High-Fidelity Electrochemical Platform Based on Au-Se Interface for Biological Detection.

Gold (Au) electrodes are one of the most ideal electrodes and are extensively used to construct electrochemical biological detection platforms. The electrode-molecule interface between the Au electrode and biomolecules is critical to the stability and efficiency of the detection platform. However, traditional Au-sulfur (Au-S) interfaces experience distortion due to high levels of glutathione (GSH) and other biological thiols in biological samples as well as a high charge barrier when electrons are injected into the biomolecule from the Au electrode. In view of the higher bonding energy of Au-selenium (Au-Se) bonds than those of Au-S bonds and the elevated Fermi energy of the Au electrodes when Au-Se bonds are formed instead of Au-S bonds at the interface between the electrodes and molecules, we establish a new type of electrochemical platform based on the Au-Se interface (Au-Se electrochemical platform) for high-fidelity biological detection. Compared with that of the electrochemical platform based on the Au-S interface (Au-S electrochemical platform), the Au-Se electrochemical platform shows a higher charge transfer rate and excellent stability in millimolar levels of GSH. The Au-Se electrochemical platform supplies an ideal solution for accurate biological detection and has great potential in biomedical detection applications.

Hydrolysis and oxidation of protein and lipids in dry-salted grass carp (Ctenopharyngodon idella) as affected by partial substitution of NaCl with KCl and amino acids.

To obtain healthier meat products with reduced Na content, the salt substitute containing l-histidine and l-lysine was compared with NaCl in the hydrolysis and oxidation of protein and lipids of dry-salted fish during processing. Compared with NaCl-treated fish (S-F), salt substitute treated fish (SS-F) had a lower Na content, higher moisture content and lower hardness. Sensory analysis showed that salt substitute didn't affect the acceptability of salted fish. The free fatty acids of SS-F treated fish had a slight tendency toward lipolysis at the end of processing. Additionally, the conjugated diene value, lipoxygenase activity and malondialdehyde value were lower in the ventral and dorsal muscles for the SS-F treatment. Meanwhile, the protein carbonyls and thiol groups were significantly decreased as cathepsin B and L activities and FAA content were increased in the ventral and dorsal muscles for the SS-F treatment. l-Histidine and l-lysine accelerated the hydrolysis (inhibit the oxidation) of protein and lipids in dry-salted grass carp, illustrating that l-histidine and l-lysine will be a positive approach to develop healthier meat products.