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The unique network characteristics and stimuli responsiveness of supramolecular hydrogels have rendered them highly advantageous in the field of wound dressings, showcasing unprecedented potential. However, there are few reports on a comprehensive review of supramolecular hydrogel dressings for wound repair and hemostasis. This review first introduces the major cross-linking methods for supramolecular hydrogels, which includes hydrogen bonding, electrostatic interactions, hydrophobic interactions, host–guest interactions, metal ligand coordination and some other interactions. Then, we review the advanced materials reported in recent years and then summarize the basic principles of each cross-linking method. Next, we classify the network structures of supramolecular hydrogels before outlining their forming process and propose their potential future directions. Furthermore, we also discuss the raw materials, structural design principles, and material characteristics used to achieve the advanced functions of supramolecular hydrogels, such as antibacterial function, tissue adhesion, substance delivery, anti-inflammatory and antioxidant functions, cell behavior regulation, angiogenesis promotion, hemostasis and other innovative functions in recent years. Finally, the existing problems as well as future development directions of the cross-linking strategy, network design, and functions in wound repair and hemostasis of supramolecular hydrogels are discussed. This review is proposed to stimulate further exploration of supramolecular hydrogels on wound repair and hemostasis by researchers in the future.

In clinical applications, there is a lack of wound dressings that combine efficient resistance to drug-resistant bacteria with good self-healing properties. In this study, a series of adhesive self-healing conductive antibacterial hydrogel dressings based on oxidized sodium alginate-grafted dopamine/carboxymethyl chitosan/Fe3+(OSD/CMC/Fe hydrogel)/polydopamine-encapsulated poly(thiophene-3-acetic acid) (OSD/CMC/Fe/PA hydrogel) were prepared for the repair of infected wound. The Schiff base and Fe3+coordination bonds of the hydrogel structure are dynamic bonds that can be repaired automatically after the hydrogel network is disrupted. Macroscopically, the hydrogel exhibits self-healing properties, allowing the hydrogel dressing to adapt to complex wound surfaces. The OSD/CMC/Fe/PA hydrogel showed good conductivity and photothermal antibacterial properties under near-infrared (NIR) light irradiation. In addition, the hydrogels exhibit tunable rheological properties, suitable mechanical properties, antioxidant properties, tissue adhesion properties and hemostatic properties. Furthermore, all hydrogel dressings improved wound healing in the infected full-thickness defect skin wound repair test in mice. The wound size repaired by OSD/CMC/Fe/PA3 hydrogel + NIR was much smaller (12%) than the control group treated with Tegaderm™ film after 14 days. In conclusion, the hydrogels have high antibacterial efficiency, suitable conductivity, great self-healing properties, good biocompatibility, hemostasis and antioxidant properties, making them promising candidates for wound healing dressings for the treatment of infected skin wounds.

Developing injectable antiswelling and high-strength bioactive hydrogels with wet tissue adhesiveness and a rapid gelling process to meet the requirements for rapid hemostasis, sutureless wound closure, and scar-free repair of infected skin wounds continues to have ongoing challenges. Herein, injectable, antibacterial, and antioxidant hydrogel adhesives based on poly(citric acid-co-polyethylene glycol)-g-dopamine and amino-terminated Pluronic F127 (APF) micelles loaded with astragaloside IV (AS) are prepared. The H2O2/horseradish peroxidase (HRP) system is used to cause cross-linking of the hydrogel network through oxidative coupling between catechol groups and chemical cross-linking between the catechol group and the amino group. The hydrogels exhibit a rapid gelling process, high mechanical strength, an antiswelling effect, good antioxidant property, H2O2release behavior, and degradability. In addition, the hydrogels present good wet tissue adhesiveness, high bursting pressure, excellent antibacterial activity, long-term sustained release of AS, and good biocompatibility. The hydrogels perform good hemostasis on mouse liver, rat liver, and rabbit femoral vein bleeding models and achieve much better closure and healing of skin incisions than biomedical glue and surgical sutures. Furthermore, the hydrogel dressing significantly improved the scar-free repair of MRSA-infected full thickness skin defect wounds by modulating inflammation, regulating the ratio of collagen I/III, and improving the vascularization and granulation tissue formation. Thus, AS-loaded hydrogels show huge potential as multifunctional dressings for in vivo hemostasis, sutureless wound closure, and scar-free repair of infected skin wounds.

Double-network hydrogels can be tuned to have high mechanical strength, stability, elasticity and bioresponsive properties, which can be combined to create self-healing, adhesive and antibacterial wound dressings. Compared with single-network hydrogel, double-network hydrogel shows stronger mechanical properties and better stability. In comparison with chemical bonds, the cross-linking in double networks makes them more flexible than single-network hydrogels and capable of self-healing following mechanical damage. Here, we present the stepwise synthesis of physical double-network hydrogels where hydrogen bonds and coordination reactions provide self-healing, pH-responsive, tissue-adhesive, antioxidant, photothermal and antibacterial properties, and can be removed on demand. We then explain how to carry out physical, chemical and biological characterizations of the hydrogels for use as wound dressings, yet the double-network hydrogels could also be used in different applications such as tissue engineering scaffolds, cell/drug delivery systems, hemostatic agents or in flexible wearable devices for monitoring physiological and pathological parameters. We also outline how to use the double-network hydrogels in vivo as wound dressings or hemostatic agents. The synthesis of the ureido–pyrimidinone-modified gelatin, catechol-modified polymers and the hydrogels requires 84 h, 48 h and 1 h, respectively, whereas the in vivo assays require 3.5 weeks. The procedure is suitable for users with expertise in biomedical polymer materials.

Ion-conducting hydrogels with excellent flexibility and ductility have great potential in human movements monitoring. However, some obstacles, including a small detection range, low sensitivity, low electrical conductivity, and poor stability under extreme conditions, impede their use as sensors. Herein, an ion-conducting hydrogel comprising acrylamide (AM), lauryl methacrylate (LMA), 2-acrylamido-2-methylpropanesulfonic acid (AMPS), and a water/glycerol binary solvent (named the AM-LMA-AMPS-LiCl (water/glycerol) hydrogel) is designed, which exhibits an enlarged detection range of 0%–1823% and improved transparency. Notably, the ion channel constructed using AMPS and LiCl significantly improves the sensitivity (gauge factor = 22.15 ± 2.86) of the hydrogel. The water/glycerol binary solvent endows the hydrogel with electrical and mechanical stability under extreme conditions (70 and −80 °C). Furthermore, the AM-LMA-AMPS-LiCl (water/glycerol) hydrogel exhibits antifatigue properties for 10 cycles (0%–1000%) because of noncovalent interactions such as hydrophobic interactions and hydrogen bonding. The hydrogel can be used to monitor human movements such as joint bending and perceive subtle discrepancies such as different joint bending speeds and angles, showing its great potential application in human movement monitoring, electronic skin, and wearable devices.

ABSTRACTIntroductionDrug treatment is one of the main ways of coping with disease today. For the disadvantages of drug management, thermosensitive hydrogel is used as a countermeasure, which can realize the simple sustained release of drugs and the controlled release of drugs in complex physiological environments.Areas coveredThis paper talks about thermosensitive hydrogels that can be used as drug carriers. The common preparation materials, material forms, thermal response mechanisms, characteristics of thermosensitive hydrogels for drug release and main disease treatment applications are reviewed.Expert opinionWhen thermosensitive hydrogels are used as drug loading and delivery platforms, desired drug release patterns and release profiles can be tailored by selecting raw materials, thermal response mechanisms, and material forms. The properties of hydrogels prepared from synthetic polymers will be more stable than natural polymers. Integrating multiple thermosensitive mechanisms or different kinds of thermosensitive mechanisms on the same hydrogel is expected to realize the spatiotemporal differential delivery of multiple drugs under temperature stimulation. The industrial transformation of thermosensitive hydrogels as drug delivery platforms needs to meet some important conditions.

Two-photon confocal laser microscopy was used to obtain three-dimensional (3D) images of the morphology of poly(lactic acid) after shear-induced crystallization. The necessary fluorescence contrast was achieved by doping the polymer with Nile Red. The dye gets partially rejected from the growing crystalline aggregates during their formation, thus creating a renderable high-low fluorescence boundary outlining the shape of the aggregates. Parallel-plate melt-shearing and pulling a glass fiber through the melt were used as the two methods to achieve shear-induced crystallization. This study focuses on the shape of the resulting cylindrites, i.e., large-diameter shish-kebabs. The first 3D images of polymer cylindrites show that, if far from boundaries, they are circular cylinders, highly regular after fiber pull, but less so after parallel-plate shear. In the latter case, the cylindrite reveals the trajectory of the foreign particle that had nucleated its growth. Interestingly, lateral growth of the cylindrites was found to accelerate toward the sample surface when approaching it, giving the cylindrite an elliptical cross section. Furthermore and surprisingly, in the case of fiber pull, a row of spherulites is nucleated at the polymer–substrate interface nearest to the fiber, aligned along the fiber axis and appearing ahead of the rest of the space-filling spherulites. Both the phenomena, elliptical cylindrites and row of spherulites, are attributed to negative pressure buildup peaking at the cylindrite growth front and at the nearby film surface caused by crystallization-induced volume contraction. The pressure and flow distribution in the system is confirmed by numerical simulation. The results illustrate the value of 3D imaging of crystalline morphology in polymer science and polymer processing industry.

Monoterpenoid indole alkaloids (MIAs) are among the most diverse specialized metabolites in plants and are of great pharmaceutical importance. We leveraged single-cell transcriptomics to explore the spatial organization of MIA metabolism in Catharanthus roseusleaves, and the transcripts of 20 MIA genes were first localized, updating the model of MIA biosynthesis. The MIA pathway was partitioned into three cell types, consistent with the results from RNA in situ hybridization experiments. Several candidate transporters were predicted to be essential players shuttling MIA intermediates between inter- and intracellular compartments, supplying potential targets to increase the overall yields of desirable MIAs in native plants or heterologous hosts through metabolic engineering and synthetic biology. This work provides not only a universal roadmap for elucidating the spatiotemporal distribution of biological processes at single-cell resolution, but also abundant cellular and genetic resources for further investigation of the higher-order organization of MIA biosynthesis, transport and storage.

Wounds on stretchable parts of the human body cause prolonged suffering and involve more severe healing processes than wounds on stationary parts. However, they have received insufficient attention compared with other types of chronic wounds. In this study, a novel supramolecular gelatin (GT) hydrogel composed of GT-graft-aniline tetramer and quaternized chitosan was presented. The hydrogel was crosslinked by monoaldehyde β-cyclodextrin via host—guest interaction and dynamic Schiff base and was free from permanent covalent bonds, heavy metals, and oxidants. Given its dynamic feature, the hydrogel exhibited flexibility, self-healing, and tissue adhesiveness and well adapted to motion wounds. Moreover, the hydrogel was bioactive with conductivity, antioxidant property, hemostatic effect, antibacterial, and photothermal effect (the killing ratio for methicillin-resistant Staphylococcus aureus(MRSA) was higher than 99.8% after 5 min of near-infrared irradiation) and exhibited on-demand removability. In the full-thickness MRSA-infected motional wound healing experiment, this novel hydrogel exhibited a significantly enhanced wound healing efficacy with a fast wound closure ratio (about 99.0% for 14 days), mild inflammatory response, high level of collagen deposition, and enhanced re-epithelialization by downregulating interleukin-6 and CD68 and upregulating vascular endothelial growth factor. The results indicated that this hydrogel has great potential in wound healing and skin tissue engineering and serves as an inspiration for the design of supramolecular biomaterials.

The on-demand replacement of multifunctional hydrogel wound dressings helps to avoid bacterial colonization, and the on-demand painless peeling of tissue adhesive hydrogels on the wound site remains a major challenge to be solved. In this work, we design and develop a series of multifunctional dynamic Schiff base network hydrogels composed of cystamine-modified hyaluronic acid, benzaldehyde-functionalized poly(ethylene glycol)-co-poly(glycerol sebacate), and polydopamine@polypyrrole nanocomposite (PDA@PPy) with mild on-demand removability to enhance drug-resistant bacteria-infected wound healing. These hydrogels exhibited ideal injectable and self-healing properties, excellent tissue adhesion, in vivo hemostasis, good antioxidation, and conductivity. PDA@PPy inspired by melanin endows hydrogels with excellent antioxidant capacity, UV-blocking ability, and photothermal anti-infection ability. Based on the dynamic oxidation–reduction response of disulfide bonds inspired by the dissociation of the tertiary spatial structure transformation of poly-polypeptide chains, these hydrogels can achieve rapid painless on-demand removal under mild conditions by adding dithiothreitol. These multifunctional hydrogels significantly promoted collagen deposition and angiogenesis in the MRSA-infected full-thickness skin repair experiment. All the results showed that these multifunctional hydrogels with painless on-demand removal property showed great potential in clinical treatment of infected wounds.

• A series of antioxidant and photothermal antibacterial dual–crosslinked cryogels was designed. • The cryogels showed stable mechanical property and biocompatibility. • These cryogels rapidly stopped irregularly shaped and non-compressible bleeding. • The cryogels significantly improved the MRSA-infected full-thickness skin defect wound healing. Cryogel dressings with good absorption ability and photothermal antibacterial properties for preventing wound infections and treating infected wounds have attracted widespread attention. In this work, a series of cryogels with macroporous structure, antioxidant and photothermal properties were prepared based on adipic dihydrazide modified hyaluronic acid (HA-ADH), and dopamine (DA). The antioxidant properties, hemostatic properties, near infrared (NIR) assisted photothermal antibacterial ability provided by polydopamine, recyclable compression mechanical properties, and cytocompatibility were tested. The results demonstrated that the HA-ADH/DA cryogels have stable mechanical properties, great antibacterial properties against E. coli (EC) and methicillin-resistant S. aureus (MRSA). The high swelling ratio due to the high water retention of HA equipped the cryogels with the capability of absorbing exuded blood and excessive tissue fluid in the infected full-thickness skin defect model of mouse. The cryogels demonstrated good cytocompatibility and antioxidant performance through cell tests and 1, 1-diphenyl-2-methylbenzohydrazino (DPPH) scavenging efficiency test. The cryogels showed enhanced blood-clotting index (BCI) and better hemostatic ability in the mouse liver trauma model and the rat deep non-compressible liver defect model compared with gauze and gelatin sponge. Furthermore, compared with commercial TegadermTM dressing in vivo , the HA-ADH/DA cryogels could greatly promote infected skin wound healing in a full-thickness infected skin defect wound model. In summary, the macroporous HA-ADH/DA cryogels with good antioxidant, high swelling ratio, photothermal antibacterial property, and biocompatibility are a promising hemostatic material and wound healing dressing. [Display omitted] [ABSTRACT FROM AUTHOR]

Bacterial infection and the ever-increasing bacterial resistance have imposed severe threat to human health. And bacterial contamination could significantly menace the wound healing process. Considering the sophisticated wound healing process, novel strategies for skin tissue engineering are focused on the integration of bioactive ingredients, antibacterial agents included, into biomaterials with different morphologies to improve cell behaviors and promote wound healing. However, a comprehensive review on anti-bacterial wound dressing to enhance wound healing has not been reported. In this review, various antibacterial biomaterials as wound dressings will be discussed. Different kinds of antibacterial agents, including antibiotics, nanoparticles (metal and metallic oxides, light-induced antibacterial agents), cationic organic agents, and others, and their recent advances are summarized. Biomaterial selection and fabrication of biomaterials with different structures and forms, including films, hydrogel, electrospun nanofibers, sponge, foam and three-dimension (3D) printed scaffold for skin regeneration, are elaborated discussed. Current challenges and the future perspectives are presented in this multidisciplinary field. We envision that this review will provide a general insight to the elegant design and further refinement of wound dressing.

Thalamocortical (TC) circuits are essential for sensory information processing. Clinical and preclinical studies of autism spectrum disorders (ASDs) have highlighted abnormal thalamic development and TC circuit dysfunction. However, mechanistic understanding of how TC dysfunction contributes to behavioral abnormalities in ASDs is limited. Here, our study on a Shank3mouse model of ASD reveals TC neuron hyperexcitability with excessive burst firing and a temporal mismatch relationship with slow cortical rhythms during sleep. These TC electrophysiological alterations and the consequent sensory hypersensitivity and sleep fragmentation in Shank3mutant mice are causally linked to HCN2 channelopathy. Restoring HCN2 function early in postnatal development via a viral approach or lamotrigine (LTG) ameliorates sensory and sleep problems. A retrospective case series also supports beneficial effects of LTG treatment on sensory behavior in ASD patients. Our study identifies a clinically relevant circuit mechanism and proposes a targeted molecular intervention for ASD-related behavioral impairments.

Wound refers to the place where human body is injured and ruptured. So, wounds in a broad sense include not only skin wounds, but also damages of muscle, corneal, heart, and lung, etc. As “gold standard” of wound closure, suture and staple cause secondary damage to the tissue, and require professional skills and equipment, so noninvasive hydrogel adhesives have been developed as an alternative to close and treat different kinds of wounds. However, the existing reviews mainly discussed the research of hydrogel adhesives for skin wounds, and the focus is mostly on its types and adhesion mechanisms, but a review comprehensively discusses the design and application of hydrogel adhesives on generalized wounds for wound closure and wound healing and the unique needs of various wounds for hydrogel adhesives is still lacking. In this review, the types and adhesion mechanisms of hydrogel adhesives will be briefly described, then the research progress of hydrogel adhesives in wound treatment is reviewed in detail from two aspects: the comprehensive design principles and the unique requirements of different types of wounds. Overall, we expect that this review will provide guidance for the development of hydrogel adhesives as new avenues for generalized wound care and treatment.

Biomineralized tough hydrogels (BTHs) have advanced applications in the fields of soft bioelectronics and biomimetic tissue engineering. But the development of rapid and general photomineralization strategies for one-step fabrication of customizable BTHs is still a challenging task. Here we report a straightforward, low-cost visible-light-mediated nano-biomineralization (VLMNB) strategy viaa rational design of a phosphate source and efficient ruthenium photochemistry. Multinetwork tough hydrogels are simultaneously constructed under the same condition. Therefore, BTHs are rapidly prepared in a short time as low as ∼60 s under visible light irradiation. The in situformation of calcium phosphate particles can improve BTHs’ mechanical and biological properties and reduce the friction coefficient with bones. Furthermore, fast biomineralization and solidification processes in these BTHs benefit their injectable and highly flexible customizable design, showing applications of promoting customizable skin repair and bone regeneration.

With the increasing prevalence of drug-resistant bacterial infections and the slow healing of chronically infected wounds, the development of new antibacterial and accelerated wound healing dressings has become a serious challenge. In order to solve this problem, we developed photo-crosslinked multifunctional antibacterial adhesive anti-oxidant hemostatic hydrogel dressings based on polyethylene glycol monomethyl ether modified glycidyl methacrylate functionalized chitosan (CSG-PEG), methacrylamide dopamine (DMA) and zinc ion for disinfection of drug-resistant bacteria and promoting wound healing. The mechanical properties, rheological properties and morphology of hydrogels were characterized, and the biocompatibility of these hydrogels was studied through cell compatibility and blood compatibility tests. These hydrogels were tested for the in vitro blood-clotting ability of whole blood and showed good hemostatic ability in the mouse liver hemorrhage model and the mouse-tail amputation model. In addition, it has been confirmed that the multifunctional hydrogels have good inherent antibacterial properties against Methicillin-resistant Staphylococcus aureus(MRSA). In the full-thickness skin defect model infected with MRSA, the wound closure ratio, thickness of granulation tissue, number of collagen deposition, regeneration of blood vessels and hair follicles were measured. The inflammation-related cytokines (CD68) and angiogenesis-related cytokines (CD31) expressed during skin regeneration were studied. All results indicate that these multifunctional antibacterial adhesive hemostatic hydrogels have better healing effects than commercially available Tegaderm™ Film, revealing that they have become promising alternative in the healing of infected wounds.

Bone defect repair is one of the most common issues in clinic. Developmental multifunctional scaffolds have become a promising strategy to effectively promote bone defect repair. Here, a series of multifunctional hydrogels that integrate stable mechanical properties, non-swelling property, conductivity, and photothermal antibacterial properties were developed based on gelatin methacrylate (GM), acryloyl-β-cyclodextrin (Ac-CD), and β-cyclodextrin (β-CD)-functionalized reduced graphene oxide (rGO) for skull defect regeneration. Ac-CD was added as a host macromolecule to improve the toughness of the hydrogels. rGO was selected as the conductive element to endow the hydrogel with conductive properties, and the β-CD unit in rGO allowed rGO to interact with GM to improve the dispersity of rGO. In vitro/in vivostudies confirmed that the GM/Ac-CD/rGO hydrogel had good biocompatibility and simultaneously promoted the proliferation and osteogenic differentiation of MC3T3-E1 cells, and further accelerated in vivobone defect repair in a rat skull defect model. Moreover, two-photon laser scanning microscopy (TPLSM) was used for the first time to evaluate bone defect repair by exploring the collagen and mineralized structure directly in bone defect specimens. In short, these multifunctional hydrogels have shown promising applications in bone tissue formation and further accelerate bone defect repair, indicating their great potential for clinical application.

Electrospun nanofibers have been extensively studied in the biomedical field, including the controlled release of drugs, bionics, cell scaffolds, hemostasis, wound healing, and tissue engineering because of their high porosity, large surface area-to-volume ratio, and programmable features. In recent years researchers have continuously broadened the structural design of electrospun nanofibers, which have evolved from one-dimensional to three-dimensional structures, in order to diversify their function. These properties enable nanofibers to structurally and functionally mimic natural extracellular matrix (ECM), thereby obtaining a favorable physiological microenvironment for both wound healing and hemostasis due to improved blood coagulation and concentration. A comprehensive review summarizing the recent research progress of the structural and functional design of electrospun nanofibers for hemostasis and wound healing, on the other hand, is lacking. This review summarizes electrospun nanofibers used for hemostasis and wound healing, with a focus on structural design and modification strategies. The wide application of electrospun nanofibers in hemostasis and wound healing is clarified using a special structural and innovative design for electrospinning. The advantages and limitations of electrospun nanofibers with various structural forms are also discussed, as are the main challenges and future development directions for the development of structurally specific electrospun nanofibers for hemostasis and wound healing.

Hydrogels, due to their excellent biochemical and mechnical property, have shown attractive advantages in the field of wound dressings. However, a comprehensive review of the functional hydrogel as a wound dressing is still lacking. This work first summarizes the skin wound healing process and relates evaluation parameters and then reviews the advanced functions of hydrogel dressings such as antimicrobial property, adhesion and hemostasis, anti-inflammatory and anti-oxidation, substance delivery, self-healing, stimulus response, conductivity, and the recently emerged wound monitoring feature, and the strategies adopted to achieve these functions are all classified and discussed. Furthermore, applications of hydrogel wound dressing for the treatment of different types of wounds such as incisional wound and the excisional wound are summarized. Chronic wounds are also mentioned, and the focus of attention on infected wounds, burn wounds, and diabetic wounds is discussed. Finally, the future directions of hydrogel wound dressings for wound healing are further proposed.

Partial‐thickness cartilage defect (PTCD) is a common and formidable clinical challenge without effective therapeutic approaches. The inherent anti‐adhesive characteristics of the extracellular matrix within cartilage pose a significant impediment to the integration of cells or biomaterials with the native cartilage during cartilage repair. Here, an injectable photocrosslinked bioadhesive hydrogel, consisting of gelatin methacryloyl (GM), acryloyl‐6‐aminocaproic acid‐g‐N‐hydroxysuccinimide (AN), and poly(lactic‐co‐glycolic acid) microspheres loaded with kartogenin (KGN) (abbreviated as GM/AN/KGN hydrogel), is designed to enhance interfacial integration and repair of PTCD. After injected in situ at the irregular defect, a stable and robust hydrogel network is rapidly formed by ultraviolet irradiation, and it can be quickly and tightly adhered to native cartilage through amide bonds. The hydrogel exhibits good adhesion strength up to 27.25 ± 1.22 kPa by lap shear strength experiments. The GM/AN/KGN hydrogel demonstrates good adhesion, low swelling, resistance to fatigue, biocompatibility, and chondrogenesis properties in vitro. A rat model with PTCD exhibits restoration of a smoother surface, stable seamless integration, and abundant aggrecan and type II collagen production. The injectable stable adhesive hydrogel with long‐term chondrogenic differentiation capacity shows great potential to facilitate repair of PTCD. Gelatin methacryloyl (GM), acryloyl‐6‐aminocaproic acid‐g‐N‐hydroxysuccinimide (AN), and kartogenin (KGN) microspheres are used to fabricate the GM/AN/KGN hydrogel. After injected in situ and exposed to ultraviolet light, the GM/AN/KGN hydrogel achieves stable adhesion to the cartilage through amide bonds. This process promotes seamless integration between the hydrogel and cartilage and facilitating cartilage repair through the sustained release of KGN.

There is still an urgent need to develop hydrogels with intelligent antibacterial ability to achieve on-demand treatment of infected wounds and accelerate wound healing by improving the regeneration microenvironment. We proposed a strategy of hydrogel wound dressing with bacteria-responsive self-activating antibacterial property and multiple nanozyme activities to remodel the regeneration microenvironment in order to significantly promote infected wound healing. Specifically, pH-responsive H2O2self-supplying composite nanozyme (MSCO) and pH/enzyme-sensitive bacteria-responsive triblock micelles encapsulated with lactate oxidase (PPEL) were prepared and encapsulated in hydrogels composed of L-arginine-modified chitosan (CA) and phenylboronic acid-modified oxidized dextran (ODP) to form a cascade bacteria-responsive self-activating antibacterial composite hydrogel platform. The hydrogels respond to multifactorial changes of the bacterial metabolic microenvironment to achieve on-demand antibacterial and biofilm eradication through transformation of bacterial metabolites, and chemodynamic therapy enhanced by nanozyme activity in conjunction with self-driven nitric oxide (NO) release. The composite hydrogel showed ‘self-diagnostic’ treatment for changes in the wound microenvironment. Through self-activating antibacterial therapy in the infection stage to self-adaptive oxidative stress relief and angiogenesis in the post-infection stage, it promotes wound closure, accelerates wound collagen deposition and angiogenesis, and completely improves the microenvironment of infected wound regeneration, which provides a new method for the design of intelligent wound dressings.A self-activated on-demand antibacterial hydrogel based on bacterial infection microenvironment response is proposed for remodeling the regenerative microenvironment of infected motion wounds and accelerating wound healing.

Elevated temperatures can deactivate tissues in the burn wound area, allowing pathogenic bacteria to multiply on the wound surface, ultimately leading to local or systemic infection. An ideal burn dressing should provide antibacterial properties and facilitate painless dressing changes. Silk microfibers coated with poly (2, 3, 4‐trihydroxybenzaldehyde) (referred to as mSF@PTHB) to in situ reduce AgNO3to silver nanoparticles (AgNPs) in a hydrazide hyaluronic acid‐based hydrogel are utilized. The findings indicate a more homogeneous distribution of the silver elements compared to directly doped AgNPs, which also conferred antioxidant and antibacterial properties to the hydrogel. Moreover, hydrogels containing pH‐responsive dynamic acylhydrazone bonds can undergo a gel‐sol transition in a weak acid environment, leading to the painless removal of adhesive hydrogel dressings. Notably, the on‐demand replaceable self‐healing antioxidant hydrogel dressing exhibits antibacterial effects and cytocompatibility in vitro, and the wound‐healing performance of the hydrogel is validated by treating a burn mouse model with full‐thickness skin defects. It is demonstrated that hydrogel dressings offer a viable therapeutic approach to prevent infection and facilitate the healing of burn wounds. An ideal burn dressing should provide antibacterial properties and facilitate painless dressing changes. Silk microfibers coated with poly (2, 3, 4‐trihydroxybenzaldehyde) to in situ reduce AgNO3into AgNPs, endowing hydrogel with antibacterial and photothermal enhancement of Ag+release properties are employed. Additionally, the hydrogels undergo a gel‐sol transition in a weak acid environment, facilitating painless removal of adhesive hydrogel dressings.

A two-pronged strategy of biomechanically active and biochemically functional hydrogel wound dressing which can assist wound closure and have multiple functions to promote wound healing has been rarely reported. Herein, we designed a series of biomechanically active injectable self-healing hydrogels based on quaternized chitosan (QCS), polydopamine-coated reduction graphene oxide (rGO-PDA), and poly(N-isopropylacrylamide) (PNIPAm) as multifunctional wound dressings to promote wound closure and wound healing. These biomechanically active wound dressings have excellent thermoresponsive self-contraction and tissue adhesion properties. They adhere strongly to the skin and assist wound closure by actively contracting wounds through self-contraction. Moreover, these hydrogels exhibit biochemical multifunctions that are beneficial to wound healing, including good self-healing property, temperature-dependent drug release ability, anti-infection, antioxidation, and conductivity. The in vivo full-thickness skin defect model demonstrates that the hydrogel dressings significantly promoted wound closure with accelerated wound contraction and promoted the wound-healing process with higher granulation tissue thickness, collagen disposition, and enhanced vascularization. In summary, the biomechanically active injectable self-healing conductive adhesive hydrogels promoted wound healing by assisting wound closure and biochemical functions, opening a two-pronged strategy approach to wound management through combining biomechanical and biochemical functions together.

A survey of the literature related to theoretical and experimental studies on stick–slip vibration in oilwell drillstring is carried out in this study. It aims to explain key concepts and present the existing methods for studying this phenomenon. After briefly describing the stick–slip vibration related problems, theoretical models for such phenomenon are discussed including both coupled and uncoupled models. Discussion for experimental investigations including both laboratory and field tests are hereinafter addressed. This study aims to summarize the literature related to the stick–slip vibration, and help researchers in understanding and suppressing such phenomenon.

Recent success in identifying gene-regulatory elements in the context of recombinant adeno-associated virus vectors has enabled cell-type-restricted gene expression. However, within the cerebral cortex these tools are largely limited to broad classes of neurons. To overcome this limitation, we developed a strategy that led to the identification of multiple new enhancers to target functionally distinct neuronal subtypes. By investigating the regulatory landscape of the disease gene Scn1a, we discovered enhancers selective for parvalbumin (PV) and vasoactive intestinal peptide-expressing interneurons. Demonstrating the functional utility of these elements, we show that the PV-specific enhancer allowed for the selective targeting and manipulation of these neurons across vertebrate species, including humans. Finally, we demonstrate that our selection method is generalizable and characterizes additional PV-specific enhancers with exquisite specificity within distinct brain regions. Altogether, these viral tools can be used for cell-type-specific circuit manipulation and hold considerable promise for use in therapeutic interventions.

Cryogels with tissue adhesion have great potential as wound dressings for rapid hemostasis for uncontrollable nonpressing surface hemorrhage and wound healing, but their use has not been reported previously. Herein, we designed a series of antibacterial and antioxidant tissue-adhesive cryogels based on quaternized chitosan (QCS) and polydopamine (PDA). These cryogels had good blood cell and platelet adhesion, enrichment, and activation properties for rapid nonpressing surface hemostasis and wound healing. The cryogels exhibited outstanding mechanical strength and easy removability, antioxidant activity, and NIR photothermal-enhanced antibacterial performance. The cryogels showed much better hemostasis than gauze and gelatin sponge in a standardized strip rat liver injury model, a standardized circular rabbit liver section model, and a pig skin laceration model. Furthermore, the excellent hemostatic performance of the QCS/PDA2.0 cryogel (containing 20 mg/mL QCS and 2.0 mg/mL PDA) for coagulopathic hemorrhages was confirmed in a standardized coagulation disorder rabbit circular liver section model. In addition, the QCS/PDA2.0 cryogel promoted rapid hemostasis in a deep noncompressible wound and a much better wound healing effect than a chitosan sponge and Tegaderm film in a full-thickness skin defect model. Overall, these multifunctional tissue-adhesive cryogels with excellent hemostatic performance and enhanced wound healing properties are suitable candidates for tissue-adhesive hemostat and wound healing dressings.

Biodegradable cryogel wound dressing which can stop deep noncompressible hemorrhage and simultaneously promote wound healing is a highly promising biomaterial in clinics. Here, we prepared a series of biodegradable interpenetrating polymer network (IPN) dry cryogel hemostats by cryo-polymerization of gelatin and dopamine. The IPN structure of cross-linked gelatin and polydopamine endows the cryogels good injectability, robust mechanical property, and shape memory property. The cryogels showed better whole blood-clotting capacity and more blood cell and platelet adhesion and activation than gauze and gelatin hemostatic sponge. The cryogels present less blood loss and shorter hemostasis time than gauze and gelatin hemostatic sponges in the mouse liver trauma model, rat liver incision model, and rabbit liver cross incision model. Especially, the hemostatic effect of the cryogel on deep narrow noncompressible hemorrhage was determined by the rabbit liver defect deep narrow noncompressible hemorrhage model. The cryogel rapidly stopped deep massive noncompressible hemorrhage in the swine subclavian artery and vein complete transection model. Besides, the component of polydopamine endows cryogels with excellent antioxidant activity and NIR irradiation-assisted photothermal antibacterial ability. Gelatin/dopamine cryogels were more effective in promoting wound healing than Tegaderm films. The developed biodegradable cryogels with a simple preparation process and low cost and which can be easily carried and used present huge potential as novel wound dressing for rapid hemostasis and promoting wound healing.

The thalamic reticular nucleus (TRN), the major source of thalamic inhibition, regulates thalamocortical interactions that are critical for sensory processing, attention and cognition1–5. TRN dysfunction has been linked to sensory abnormality, attention deficit and sleep disturbance across multiple neurodevelopmental disorders6–9. However, little is known about the organizational principles that underlie its divergent functions. Here we performed an integrative study linking single-cell molecular and electrophysiological features of the mouse TRN to connectivity and systems-level function. We found that cellular heterogeneity in the TRN is characterized by a transcriptomic gradient of two negatively correlated gene-expression profiles, each containing hundreds of genes. Neurons in the extremes of this transcriptomic gradient express mutually exclusive markers, exhibit core or shell-like anatomical structure and have distinct electrophysiological properties. The two TRN subpopulations make differential connections with the functionally distinct first-order and higher-order thalamic nuclei to form molecularly defined TRN–thalamus subnetworks. Selective perturbation of the two subnetworks in vivo revealed their differential role in regulating sleep. In sum, our study provides a comprehensive atlas of TRN neurons at single-cell resolution and links molecularly defined subnetworks to the functional organization of thalamocortical circuits.

The development of a highly effective photosensitizer (PS) that can be activated with a low-power single light is a pressing issue. Herein, we report a PS for synergistic photodynamic and photothermal therapy constructed through self-assembly of poly(selenoviologen) on the surface of core-shell NaYF4:Yb/Tm@NaYF4upconversion nanoparticles. The hybrid UCNPs/PSeV PS showed strong ROS generation ability and high photothermal conversion efficiency (∼52.5%) under the mildest reported-to-date irradiation conditions (λ = 980 nm, 150 mW/cm2, 4 min), leading to a high efficiency in killing methicillin-resistant Staphylococcus aureus(MRSA) both in vitroand in vivo. Remarkably, after intravenous injection, the reported PS accumulated preferentially in deep MRSA-infected tissues and achieved an excellent therapeutic index. This PS design realizes a low-power single-NIR light-triggered synergistic phototherapy and provides a simple and versatile strategy to develop safe clinically translatable agents for efficient treatment of deep tissue bacterial inflammations.

As the abuse of antibiotics continues to increase, the emergence of antibiotic resistance and unknown drug-resistant bacterial infections pose a great threat on people worldwide. In this work, we aimed to develop a series of injectable antimicrobial conductive hydrogels based on glycidyl methacrylate functionalized quaternized chitosan (QCSG), gelatin methacrylate (GM), and graphene oxide (GO) for drug-resistant bacterial disinfection and infectious wound healing. The rheology, morphology, mechanical properties, and electrical and photothermal properties of the hydrogels were characterized. Furthermore, the good in vitro and in vivo intrinsic antibacterial, photothermal antibacterial, and antibiotics released antibacterial properties of this multiantibacterial hydrogel were verified. The good biocompatibility of these hydrogels was also investigated by cytocompatibility, hemocompatibility, and histocompatibility tests. In the drug-resistant Methicillin-resistant Staphylococcus aureus(MRSA) infected mouse full-thickness defect model, the wound closure rate, the length of dermal tissue gap, number of blood vessels and hair follicles in hematoxylin-eosin (HE) staining, the amount of collagen in Masson staining, and the related cytokines for the expression of inflammation (interleukin-6, IL-6) and regeneration of blood vessels (vascular endothelial growth factor, VEGF) in immunofluorescence were all further studied. All the results demonstrated the better wound healing effect of these multiantibacterial injectable conductive hydrogel in infectious skin tissue defect repair, indicating their great potential for infected wound healing.

Hyper-reactivity to sensory input is a common and debilitating symptom in individuals with autism spectrum disorders (ASD), but the neural basis underlying sensory abnormality is not completely understood. Here we examined the neural representations of sensory perception in the neocortex of a Shank3B−/−mouse model of ASD. Male and female Shank3B−/−mice were more sensitive to relatively weak tactile stimulation in a vibrissa motion detection task. In vivo population calcium imaging in vibrissa primary somatosensory cortex (vS1) revealed increased spontaneous and stimulus-evoked firing in pyramidal neurons but reduced activity in interneurons. Preferential deletion of Shank3in vS1 inhibitory interneurons led to pyramidal neuron hyperactivity and increased stimulus sensitivity in the vibrissa motion detection task. These findings provide evidence that cortical GABAergic interneuron dysfunction plays a key role in sensory hyper-reactivity in a Shank3mouse model of ASD and identify a potential cellular target for exploring therapeutic interventions.