Seeking Cells, Targeting Bacteria: A Cascade-Targeting Bacteria-Responsive Nanosystem for Combating Intracellular Bacterial Infections.

Intracellular bacteria pose a great challenge to antimicrobial therapy due to various physiological barriers at both cellular and bacterial levels, which impede drug penetration and intracellular targeting, thereby fostering antibiotic resistance and yielding suboptimal treatment outcomes. Herein, a cascade-target bacterial-responsive drug delivery nanosystem, MM@SPE NPs, comprising a macrophage membrane (MM) shell and a core of SPE NPs. SPE NPs consist of phenylboronic acid-grafted dendritic mesoporous silica nanoparticles (SP NPs) encapsulated with epigallocatechin-3-gallate (EGCG), a non-antibiotic antibacterial component, via pH-sensitive boronic ester bonds are introduced. Upon administration, MM@SPE NPs actively home in on infected macrophages due to the homologous targeting properties of the MM shell, which is subsequently disrupted during cellular endocytosis. Within the cellular environment, SPE NPs expose and spontaneously accumulate around intracellular bacteria through their bacteria-targeting phenylboronic acid groups. The acidic bacterial microenvironment further triggers the breakage of boronic ester bonds between SP NPs and EGCG, allowing the bacterial-responsive release of EGCG for localized intracellular antibacterial effects. The efficacy of MM@SPE NPs in precisely eliminating intracellular bacteria is validated in two rat models of intracellular bacterial infections. This cascade-targeting responsive system offers new solutions for treating intracellular bacterial infections while minimizing the risk of drug resistance.

Engineered Cell Membrane-Coated Nanoparticles: New Strategies in Glioma Targeted Therapy and Immune Modulation.

Gliomas, the most prevalent primary brain tumors, pose considerable challenges due to their heterogeneity, intricate tumor microenvironment (TME), and blood-brain barrier (BBB), which restrict the effectiveness of traditional treatments like surgery and chemotherapy. This review provides an overview of engineered cell membrane technologies in glioma therapy, with a specific emphasis on targeted drug delivery and modulation of the immune microenvironment. This study investigates the progress in engineered cell membranes, encompassing physical, chemical, and genetic alterations, to improve drug delivery across the BBB and effectively target gliomas. The examination focuses on the interaction of engineered cell membrane-coated nanoparticles (ECM-NPs) with the TME in gliomas, emphasizing their potential to modulate glioma cell behavior and TME to enhance therapeutic efficacy. The review further explores the involvement of ECM-NPs in immunomodulation techniques, highlighting their impact on immune reactions. While facing obstacles related to membrane stability and manufacturing scalability, the review outlines forthcoming research directions focused on enhancing membrane performance. This review underscores the promise of ECM-NPs in surpassing conventional therapeutic constraints, proposing novel approaches for efficacious glioma treatment.

Antibacterial and antioxidant bifunctional hydrogel based on hyaluronic acid complex MoS2-dithiothreitol nanozyme for treatment of infected wounds.

Wound repair is a complex physiological process that often leads to bacterial infections, which significantly threaten human health. Therefore, developing wound-healing materials that promote healing and prevent bacterial infections is crucial. In this study, the coordination interaction between sulfhydryl groups on dithiothreitol (DTT) and MoS2 nanosheets is investigated to synthesize a MoS2-DTT nanozyme with photothermal properties and an improved free-radical scavenging ability. Double-bond-modified hyaluronic acid is used as a monomer and is cross-linked with a PF127-DA agent. PHMoD is prepared in coordination with MoS2-DTT as the functional component. This hydrogel exhibits antioxidant and antibacterial properties, attributed to the catalytic activity of catalase-like enzymes and photothermal effects. Under the near-infrared (NIR), it exhibits potent antibacterial effects against gram-positive (Staphylococcus aureus) and gram-negative bacteria (Escherichia coli), achieving bactericidal rates of 99.76% and 99.42%, respectively. Furthermore, the hydrogel exhibits remarkable reactive oxygen species scavenging and antioxidant capabilities, effectively countering oxidative stress in L929 cells. Remarkably, in an animal model, wounds treated with the PHMoD(2.0) and NIR laser heal the fastest, sealing completely within 10 days. These results indicate the unique biocompatibility and bifunctionality of the PHMoD, which make it a promising material for wound-healing applications.

A tough and bioadhesive injectable hydrogel formed with maleimidyl alginate and pristine gelatin.

Injectable hydrogels have wide applications in clinical practice. However, the development of tough and bioadhesive ones based on biopolymers, along with biofriendly and robust crosslinking strategies, still represents a great challenge. Herein, we report an injectable hydrogel composed of maleimidyl alginate and pristine gelatin, for which the precursor solutions could self-crosslink via mild Michael-type addition without any catalyst or external energy upon mixing. This hydrogel is tough and bioadhesive, which can maintain intactness as well as adherence to the defect of porcine skin under fierce bending and twisting, warm water bath, and boiling water shower. Besides, it is biocompatible, bioactive and biodegradable, which could support the growth and remodeling of cells by affording an extracellular matrix-like environment. As a proof of application, we demonstrate that this hydrogel could significantly accelerate diabetic skin wound healing, thereby holding great potential in healthcare.

Orchestrating Precision within the Tumor Microenvironment by Biomimetic Nanoprodrugs for Effective Tumor Therapy.

Malignant tumors are still one of the most deadly diseases that threaten human life and health. However, developing new drugs is challenging due to lengthy trials, funding constraints, and regulatory approval procedures. Consequently, researchers have devoted themselves to transforming some clinically approved old drugs into antitumor drugs with certain active ingredients, which have become an attractive alternative. Disulfiram (DSF), an antialcohol medication, can rapidly metabolize in the physiological environment into diethyldithiocarbamate (DTC) which can readily react with Cu2+ ions in situ to form the highly toxic bis(N,N-diethyldithiocarbamate)-copper(II) (CuET) complex. In this study, DSF is loaded into mesoporous dopamine nanocarriers and surface-chelated with tannin and Cu2+ to construct M-MDTC nanoprodrugs under the camouflage of K7 tumor cell membranes. After intravenous injection, M-MDTC nanoprodrugs successfully reach the tumor sites with the help of mediated cell membranes. Under slightly acidic pH and photothermal stimulation conditions, DSF and Cu2+ are simultaneously released, forming a highly toxic CuET to kill tumor cells in situ. The generated CuET can also induce immunogenic cell death of tumor cells, increase the proportion of CD86+ CD80+ cells, and promote dendritic cell maturation. In vitro and in vivo studies of M-MDTC nanoprodrugs have shown excellent tumor-cell-killing ability and solid tumor suppression. This approach enables in situ amplification of chemotherapy in the tumor microenvironment, achieving an effective antitumor treatment.

Fundamentals of Unanticipated Efficiency of Gd2O3-based Catalysts in Oxidative Coupling of Methane.

Improving the selectivity in the oxidative coupling of methane to ethane/ethylene poses a significant challenge for commercialization. The required improvements are hampered by the uncertainties associated with the reaction mechanism due to its complexity. Herein, we report about 90 % selectivity to the target products at 11 % methane conversion over Gd2O3-based catalysts at 700 °C using N2O as the oxidant. Sophisticated kinetic studies have suggested the nature of adsorbed oxygen species and their binding strength as key parameters for undesired methane oxidation to carbon oxides. These descriptors can be controlled by a metal oxide promoter for Gd2O3.

Study of Injectable Hydrogel Based on ALN/nHA Promoting Osteogenesis and Inhibiting Osteoclasts in Osteoporotic Bone Defects Repair.

Osteoporotic bone defects cannot withstand surgery with more significant trauma due to bone fragility, while systemic drug therapy has formidable adverse effects. Consequently, the present study introduces an innovatively devised injectable double-crosslinked hydrogel, as a potential therapeutic avenue for addressing varied shapes of osteoporotic bone defects via a minimally invasive approach. The injectable hydrogel is formed by the formation of Schiff base bonds between oxidized sodium alginate (OSA) and carboxymethyl chitosan, and the polymerization of gelatin methacrylate by UV light crosslinking. Additionally, alendronate sodium (ALN) is loaded into the hydrogel through Schiff base formation with OSA, and nanohydroxyapatite (nHA) is incorporated into the hydrogel via blending. The hydrogel demonstrates excellent injectability, and the nHA improves the mechanical properties of hydrogel and can promote bone formation. In addition, the hydrogel can sustain the release of ALN, which has the effect of inhibiting osteoclasts. Cell studies indicate that the hydrogel can promote the differentiation of osteoblasts and inhibit the activity of osteoclast, so as to obtain better osteogenic effect. Therefore, the injectable hydrogel can be used to repair osteoporotic bone defects through a minimally invasive, simple treatment modality.

Natural Underwater Bioadhesive Offering Cohesion Modulation via Hydrogen Bond Disruptor: A Highly Injectable and in Vivo Stable Remedy for Gastric Ulcer Resolution.

Injectable bioadhesives are attractive for managing gastric ulcers through minimally invasive procedures. However, the formidable challenge is to develop bioadhesives that exhibit high injectability, rapidly adhere to lesion tissues with fast gelation, provide reliable protection in the harsh gastric environment, and simultaneously ensure stringent standards of biocompatibility. Here, a natural bioadhesive with tunable cohesion is developed based on the facile and controllable gelation between silk fibroin and tannic acid. By incorporating a hydrogen bond disruptor (urea or guanidine hydrochloride), the inherent network within the bioadhesive is disturbed, inducing a transition to a fluidic state for smooth injection (injection force <5 N). Upon injection, the fluidic bioadhesive thoroughly wets tissues, while the rapid diffusion of the disruptor triggers instantaneous in situ gelation. This orchestrated process fosters the formed bioadhesive with durable wet tissue affinity and mechanical properties that harmonize with gastric tissues, thereby bestowing long-lasting protection for ulcer healing, as evidenced through in vitro and in vivo verification. Moreover, it can be conveniently stored (≥3 m) postdehydration. This work presents a promising strategy for designing highly injectable bioadhesives utilizing natural feedstocks, avoiding any safety risks associated with synthetic materials or nonphysiological gelation conditions, and offering the potential for minimally invasive application.

A Drop-By-Drop Self-Assembled All-Natural Hydrogel as a Desensitizer for Rapid and Enduring Management of Dentin Hypersensitivity.

Dentin hypersensitivity (DH) is a prevalent dental condition arising from the exposure of dentin tubules (DTs), leading to discomfort upon external stimuli. However, achieving swift and profound occlusion of these exposed DTs for immediate and enduring relief remains challenging due to the intricate dentin structure and oral environment. Herein, a pioneering and facile drop-by-drop strategy involving an in situ generated natural supramolecular hydrogel formed by self-assembling silk fibroin (SF) and tannic acid (TA) within the narrow DT space is proposed. When SF and TA aqueous solutions are applied successively to exposed dentin, they penetrate deeply within DTs and coassemble into compact gels, robustly adhering to DT walls. This yields a rapid and compact occlusion effect with an unprecedented depth exceeding 250 µm, maintaining stable occlusion efficacy even under rigorous in vitro and in vivo erosion and friction conditions for no less than 21 days. Furthermore, the biocompatibility and effective occlusion properties are verified through cell studies in simulated oral settings and an in vivo rabbit model. This study, for the first time, demonstrates the translational potential of hydrogel-based desensitizers in treating DH with prompt action, superior occlusion depth and enduring treatment benefits, holding promise as clinical-friendly restorative solutions for delicate-structured biosystems.

Synergistic reinforcement of immunogenic cell death and transformation of tumor-associated macrophages via an M1-type macrophage membrane-camouflaged ferrous-supply-regeneration nanoplatform.

The immune system's role in tumor growth and spread has led to the importance of activating immune function in tumor therapy. We present a strategy using an M1-type macrophage membrane-camouflaged ferrous-supply-regeneration nanoplatform (M1mDDTF) to synergistically reinforce immunogenic cell death (ICD) and transform tumor-associated macrophages (TAMs) against tumors. The M1mDDTF nanoparticles consist of doxorubicin-loaded dendritic mesoporous silica nanoparticles chelated with FeIII-tannic acid (FeIIITA) and coated with M1-type macrophage membranes. In the acidic tumor microenvironment, FeIIITA releases Fe2+ and generates ·OH, aided by near infrared irradiation for enhanced doxorubicin release. Furthermore, the M1mDDTF nanoplatform not only directly kills tumor cells but stimulates ICD, which can increase the proportion of CD86+ CD80+ cells and promote dendritic cell maturation. Particularly, the M1mDDTF nanoplatform can also promote the gradual polarization of TAMs into the M1-type and promote tumor cell killing. This study demonstrates the safety and multifunctionality of M1mDDTF nanoparticles, highlighting their potential for clinical tumor treatment. STATEMENT OF SIGNIFICANCE: Malignant tumors are a global concern and a major cause of death. Nanoparticles' passive targeting is ineffective and hindered by reticuloendothelial system clearance. Therefore, enhancing nanoparticle accumulation in tumors while minimizing toxicity is a challenge. Coating nanoparticles with cell membranes enhances biocompatibility, immune evasion, and specific targeting. This approach has led to the development of numerous cell membrane-mimicking nanomaterials with remarkable properties and functions. This study developed an M1-type macrophage membrane-camouflaged ferrous-supply-regeneration nanoplatform, boosting immunogenic cell death and transforming tumor-associated macrophages. Tannic acid in the tumor microenvironment reduced Fe3+ to Fe2+, generating ·OH. M1mDDTF nanosystem induced M1-type macrophage polarization, inhibiting tumor growth and triggering immune cell death. Safe and versatile, these M1mDDTF nanoparticles hold promise for clinical tumor treatment.

Bioinspired Multiscale Mineralization: From Fundamentals to Potential Applications.

The wondrous and imaginative designs of nature have always been an inexhaustible treasure trove for material scientists. Throughout the long evolutionary process, biominerals with hierarchical structures possess some specific advantages such as outstanding mechanical properties, biological functions, and sensing performances, the formation of which (biomineralization) is delicately regulated by organic component. Provoked by the subtle structures and profound principles of nature, bioinspired functional minerals can be designed with the participation of organic molecules. Because of the designable morphology and functions, multiscale mineralization has attracted more and more attention in the areas of medicine, chemistry, biology, and material science. This review provides a summary of current advancements in this extending topic. The mechanisms underlying mineralization is first concisely elucidated. Next, several types of minerals are categorized according to their structural characteristic, as well as the different potential applications of these materials. At last, a comprehensive overview of future developments for bioinspired multiscale mineralization is given. Concentrating on the mechanism of fabrication and broad application prospects of multiscale mineralization, the hope is to provide inspirations for the design of other functional materials.

Cancer Cell Membrane-Based Materials for Biomedical Applications.

The nanodelivery system provides a novel direction for disease diagnosis and treatment; however, its delivery effectiveness is restricted by the short biological half-life and inadequate tumor targeting. The immune evasion properties and homologous targeting capabilities of natural cell membranes, particularly those of cancer cell membranes (CCM), have gained significant interest. The integration of CCM and nanoparticles has resulted in the emergence of CCM-based nanoplatforms (CCM-NPs), which have gained significant attention due to their unique properties. CCM-NPs not only prolong the blood circulation time of core nanoparticles, but also direct them for homologous tumor targeting. Herein, the history and development of CCM-NPs as well as how these platforms have been used for biomedical applications are discussed. The application of CCM-NPs for cancer therapy will be described in detail. Translational efforts are currently under way and further research to address key areas of need will ultimately be required to facilitate the successful clinical adoption of CCM-NPs.

Ingenious Synergy of a Pathology-Specific Biomimetic Multifunctional Nanoplatform for Targeted Therapy in Rheumatoid Arthritis.

Based on the pathological characteristics of rheumatoid arthritis, including the overproduction of reactive oxygen species (ROS), inflammatory responses, and osteoclast differentiation, a biomimetic multifunctional nanomedicine (M-M@I) is designed. Iguratimod (IGU) is loaded, which inhibits inflammatory responses and osteoclast differentiation, into mesoporous polydopamine (MPDA), which scavenges ROS. Subsequently, the nanoparticles are coated with a cell membrane of macrophages to achieve actively targeted delivery of the nanoparticles to inflamed joints. It is shown that the M-M@I nanoparticles are taken up well by lipopolysaccharide-induced RAW 264.7 macrophages or bone marrow-derived macrophages (BMDMs). In vitro, the M-M@I nanoparticles effectively scavenge ROS, downregulate genes related to inflammation promotion and osteoclast differentiation, and reduce the proinflammatory cytokines and osteoclast-related enzymes. They also reduce the polarization of macrophages to a pro-inflammatory M1 phenotype and inhibit differentiation into osteoclasts. In mice with collagen-induced arthritis, the M-M@I nanoparticles accumulate at arthritic sites and circulate longer, significantly mitigating arthritis symptoms and bone destruction. These results suggest that the pathology-specific biomimetic multifunctional nanoparticles are effective against rheumatoid arthritis, and they validate the approach of developing multifunctional therapies that target various pathological processes simultaneously.

Hydrogel-Based Biosensors for Bacterial Infections.

Hydrogels are known to have the advantages such as good biodegradability, biocompatibility, and easy functionalization, making them ideal candidates for biosensors. Hydrogel-based biosensors that respond to bacteria-induced microenvironmental changes such as pH, enzymes, antigens, etc., or directly interact with bacterial surface receptors, can be applied for early diagnosis of bacterial infections, providing information for timely treatment while avoiding antibiotic abuse. Furthermore, hydrogel biosensors capable of both bacteria diagnosis and treatment will greatly facilitate the development of point-of-care monitoring of bacterial infections. In this review, the recent advancement of hydrogel-based biosensors for bacterial infection is summarized and discussed. First, the biosensors based on pH-sensitive hydrogels, bacterial-specific secretions-sensitive hydrogels, and hydrogels directly in contact with bacterial surfaces are presented. Next, hydrogel biosensors capable of detecting bacterial infection in the early stage followed by immediate on-demand treatment are discussed. Finally, the challenges and future development of hydrogel biosensors for bacterial infections are proposed.

Supramolecular nanoparticles based on elastin-like peptides modified capsid protein as drug delivery platform with enhanced cancer chemotherapy efficacy.

Cancer, a prevalent disease posing significant threats to human health and longevity, necessitates effective therapeutic interventions. Chemotherapy has emerged as a primary strategy following surgical procedures for combating most malignancies. Despite the considerable efficacy of conventional chemotherapeutic agents against cancer cells, their utility is hindered by profound challenges such as multidrug resistance and deleterious toxic side effects, thereby limiting their systemic application. To tackle these challenges, we have devised a promising nanomedicine platform based on a plant virus. Specifically, we have selected the cowpea melanoma mottled virus (CCMV) as our nano-delivery system owing to its monodisperse and homogeneous size, as well as its intrinsic ability for controlled self-assembly. Leveraging the potential of this platform, we have engineered CCMV-based nanoparticles functionalized with elastin-like peptides (ELPs) at their N-terminal region. The target protein, CP-ELP, was expressed via E.coli, enabling encapsulation of the model drug DOX upon structural domain modification of the protein. The resulting nanoparticles exhibit uniform size distribution, facilitating efficient internalization by tumor cells and subsequent intracellular drug release, leading to enhanced antitumor efficacy. In addition, EVLP@DOX nanoparticles were found to activate immune response of tumor microenvironment in vivo, which further inhibiting tumor growth. Our designed nanoparticles have also demonstrated remarkable therapeutic effectiveness and favorable biological safety profiles in both murine melanoma and colorectal cancer models.

A structural color hydrogel for diagnosis of halitosis and screening of periodontitis.

Oral pathogens can produce volatile sulfur compounds (VSCs), which is the main reason for halitosis and indicates the risk of periodontitis. High-sensitivity detection of exhaled VSCs is urgently desired for promoting the point-of-care testing (POCT) of halitosis and screening of periodontitis. However, current detection methods often require bulky and costly instruments, as well as professional training, making them impractical for widespread detection. Here, a structural color hydrogel for naked-eye detection of exhaled VSCs is presented. VSCs can reduce disulfide bonds within the network, leading to expansion of the hydrogel and thus change of the structural color. A linear detection range of 0-1 ppm with a detection limit of 61 ppb can be achieved, covering the typical VSC concentration in the breath of patients with periodontitis. Furthermore, visual and in situ monitoring of Porphyromonas gingivalis responsible for periodontitis can be realized. By integrating the hydrogels into a sensor array, the oral health conditions of patients with halitosis can be evaluated and distinguished, offering risk assessment of periodontitis. Combined with a smartphone capable of color analysis, POCT of VSCs can be achieved, providing an approach for the monitoring of halitosis and screening of periodontitis.

Light and Magnetism Orchestrating Aquatic Pollutant-Degradation Robots in Programmable Trajectories.

Interfacial floating robots have promising applications in carriers, environmental monitoring, water treatment, and so on. Even though, engineering smart robots with both precisely efficient navigation and elimination of water pollutants in long term remains a challenge, as the superhydrophobicity greatly lowers resistance for aquatic motion while sacrificing chemical reactivity of the surface. Here, a pollutant-removing superhydrophobic robot integrated with well-assembled iron oxide-bismuth sulfide heterojunction composite minerals, which provide both light and magnetic propulsion, and the ability of catalytic degradation, is reported. The motion velocity of the robot reaches up to 51.9 mm s-1 within only 300 ms of acceleration under the orchestration of light, and brakes rapidly (≈200-300 ms) once turn off the light. And magnetism extends the robot to work in broad range of surface tensions in any programmable trajectory. Besides, purification of polluted water is efficiently achieved in situ and the degradation efficiency exhibits eightfold enhancements under the effect of light-triggered photothermal behavior coupled with magnetic induction, overcoming the dilemma of efficient motion with catalytic superhydrophobicity. This strategy developed here provides guidelines for the explorations of high-performance smart devices.

A macrophage cell membrane-coated cascade-targeting photothermal nanosystem for combating intracellular bacterial infections.

Current antibacterial interventions encounter formidable challenges when confronting intracellular bacteria, attributable to their clustering within phagocytes, particularly macrophages, evading host immunity and resisting antibiotics. Herein, we have developed an intelligent cell membrane-based nanosystem, denoted as MM@DAu NPs, which seamlessly integrates cascade-targeting capabilities with controllable antibacterial functions for the precise elimination of intracellular bacteria. MM@DAu NPs feature a core comprising D-alanine-functionalized gold nanoparticles (DAu NPs) enveloped by a macrophage cell membrane (MM) coating. Upon administration, MM@DAu NPs harness the intrinsic homologous targeting ability of their macrophage membrane to infiltrate bacteria-infected macrophages. Upon internalization within these host cells, exposed DAu NPs from MM@DAu NPs selectively bind to intracellular bacteria through the bacteria-targeting agent, D-alanine present on DAu NPs. This intricate process establishes a cascade mechanism that efficiently targets intracellular bacteria. Upon exposure to near-infrared irradiation, the accumulated DAu NPs surrounding intracellular bacteria induce local hyperthermia, enabling precise clearance of intracellular bacteria. Further validation in animal models infected with the typical intracellular bacteria, Staphylococcus aureus, substantiates the exceptional cascade-targeting efficacy and photothermal antibacterial potential of MM@DAu NPs in vivo. Therefore, this integrated cell membrane-based cascade-targeting photothermal nanosystem offers a promising approach for conquering persistent intracellular infections without drug resistance risks. STATEMENT OF SIGNIFICANCE: Intracellular bacterial infections lead to treatment failures and relapses because intracellular bacteria could cluster within phagocytes, especially macrophages, evading the host immune system and resisting antibiotics. Herein, we have developed an intelligent cell membrane-based nanosystem MM@DAu NPs, which is designed to precisely eliminate intracellular bacteria through a controllable cascade-targeting photothermal antibacterial approach. MM@DAu NPs combine D-alanine-functionalized gold nanoparticles with a macrophage cell membrane coating. Upon administration, MM@DAu NPs harness the homologous targeting ability of macrophage membrane to infiltrate bacteria-infected macrophages. Upon internalization, exposed DAu NPs from MM@DAu NPs selectively bind to intracellular bacteria through the bacteria-targeting agent, enabling precise clearance of intracellular bacteria through local hyperthermia. This integrated cell membrane-based cascade-targeting photothermal nanosystem offers a promising avenue for conquering persistent intracellular infections without drug resistance risks.

Self-Adhesive, Strong Antifouling, and Mechanically Reinforced Methacrylate Hyaluronic Acid Cross-Linked Carboxybetaine Zwitterionic Hydrogels.

Hyaluronic acid and zwitterionic hydrogels are soft materials with poor mechanical properties. The unique structures and physiological properties make them attractive candidates for ideal hydrogel dressings, but the crux of lacking satisfying mechanical strengths and adhesive properties is still pendent. In this study, the physical cross-linking of dipole-dipole interactions of zwitterionic pairs was utilized to enhance the mechanical properties of hydrogels. The hydrogels have been prepared by copolymerizing methacrylate hyaluronic (HAGMA) with carboxybetaine methacrylamide (CBMAA) (the mass ratio of [HAGMA]/[CBMAA] is 2:5, 1:5, 1:10, or 1:20), obtaining HA-CB2.5, HA-CB5.0, HA-CB10.0, or HA-CB20.0 hydrogel. Therein, the HA-CB20.0 hydrogel with a high CBMAA content can generate a strong dipole-dipole interaction to form internal physical cross-links, exhibit stretchability and low elastic modulus, and withstand 99% compressive deformation and cyclic compression under strain at 90%. Moreover, the HA-CB20.0 hydrogel is adhesive to diverse substrates, including skin, glass, stainless steel, and plastic. The synergistic effect of HAGMA and CBMAA shows strong anti-biofouling, high water absorption, biodegradability under hyaluronidase, and biocompatibility.

A facile strategy to fabricate a skin-like hydrogel with adhesive and highly stretchable attributes through small molecule triggering toward flexible electronics.

Polyacrylamide hydrogel is a promising matrix in biomedical applications due to its biocompatibility, transparency and flexibility. However, its implementation in skin-attachable applications is impeded by its inherent deficiency in surface-adaptive adhesion and inadequate mechanical conformity to skin tissues. Herein, tris, a biocompatible small molecule with a triple hydrogen bonding cluster in its molecule structure, is introduced for the first time into a polyacrylamide hydrogel. This incorporation is achieved via a facile one-pot strategy, resulting in a highly stretchable hydrogel with an impressive strain capacity (2574.75 ± 28.19%), a human dermis tissue-compatible Young's modulus (27.89 ± 2.05 kPa) and an intrinsically universal adhesion capacity (16.66 ± 0.32 N). These superior properties are attributed to the elevated hydrogen bonding density and the plasticizing effect induced by tris, without compromising the hydrogel's excellent transparency (>90% transmittance). Moreover, by incorporating calcium ions into the resulting soft adhesive hydrogel, we demonstrate its utility in skin-like sensors, leading to a substantial enhancement in strain sensitivity and electrical conductivity, in conjunction with the plasticizing influence exerted by tris. This work offers a facile and environmentally friendly solution to fabricate ultra-stretchable adhesive polyacrylamide hydrogel matrixes for dynamic surfaces, even under large deformation, which can broaden their potential applications in integrated bioelectronics.