SEA Anemone-inspired Conducting Polymer Sensing Platform for Integrated Detection of Tumor Protein Marker and Circulating Tumor Cell.

Combining the detection of tumor protein markers with the capture of circulating tumor cells (CTCs) represents an ultra-promising approach for early tumor detection. However, current methodologies have not yet achieved the necessary low detection limits and efficient capture. Here, we introduced a novel polypyrrole nanotentacles sensing platform featuring anemone-like structures capable of simultaneously detecting protein biomarkers and capturing CTCs. The incorporation of nanotentacles significantly enhanced the electrode surface area, providing abundant active sites for antibody binding. This enhancement allowed detecting nucleus matrix protein22 (NMP22) and bladder tumor antigen (BTA) with 2.39 and 3.12 pg/mL detection limit, respectively. Furthermore, our developed sensing platform effectively captured MCF-7 cells in blood samples with a detection limit of fewer than 10 cells/mL, attributed to the synergistic multivalent binding facilitated by the specific recognition antibodies and the positive charge on the nanotentacles surface. This sensing platform demonstrated excellent detection capabilities and outstanding capture efficiency, offering a simple, accurate, and efficient strategy for early tumor detection. This article is protected by copyright. All rights reserved.

Hydrogel Coatings of Implants for Pathological Bone Repair.

Hydrogels are well-suited for biomedical applications due to their numerous advantages, such as excellent bioactivity, versatile physical and chemical properties, and effective drug delivery capabilities. Recently, hydrogel coatings have developed to functionalize bone implants which are biologically inert and cannot withstand the complex bone tissue repair microenvironment. These coatings have shown promise in addressing unique and pressing medical needs. This review begins with the major functionalized performance and interfacial bonding strategy of hydrogel coatings, with a focus on the novel external field response properties of the hydrogel. Recent advances in the fabrication strategies of hydrogel coatings and their use in the treatment of pathologic bone regeneration are highlighted. Finally, challenges and emerging trends in the evolution and application of physiological environment-responsive and external electric field-responsive hydrogel coatings for bone implants are discussed.

Localized Surface Plasmon Resonance-Enhanced Photocatalytic Antibacterial of In-situ Sprayed 0D/2D Heterojunction Composite Hydrogel for Treating Diabetic Wound.

Chronic diabetic wounds pose significant challenges due to uncontrolled bacterial infections, prolonged inflammation, and impaired angiogenesis. The rapid advancement of photo-responsive antibacterial therapy showed promise in addressing these complex issues, particularly utilizing 2D heterojunction materials, which offer unique properties. Herein, we designed an in situ sprayed Bi/BiOCl 0D/2D heterojunction composite fibrin gel with the characteristics of rapid formation and effective near-infrared activation for the treatment of non-healing diabetes-infected wounds. The sprayed composite gel can provide protective shielding for skin tissues and promote endothelial cell proliferation, vascularization, and angiogenesis. The Bi/BiOCl 0D/2D heterojunction, with its localized surface plasmon resonance (LSPR), can overcome the wide bandgap limitation of BiOCl, enhancing the generation of local heat and reactive oxygen species under near-infrared irradiation. This facilitated bacterial elimination and reduced inflammation, supporting the accelerated healing of diabetes-infected wounds. Our study underscores the potential of LSPR-enhanced heterojunctions as advanced wound therapies for chronic diabetic wounds. This article is protected by copyright. All rights reserved.

Piezo-enhanced near infrared photocatalytic nanoheterojunction integrated injectable biopolymer hydrogel for anti-osteosarcoma and osteogenesis combination therapy.

Preventing local tumor recurrence while promoting bone tissue regeneration is an urgent need for osteosarcoma treatment. However, the therapeutic efficacy of traditional photosensitizers is limited, and they lack the ability to regenerate bone. Here, a piezo-photo nanoheterostructure is developed based on ultrasmall bismuth/strontium titanate nanocubes (denoted as Bi/SrTiO3), which achieve piezoelectric field-driven fast charge separation coupling with surface plasmon resonance to efficiently generate reactive oxygen species. These hybrid nanotherapeutics are integrated into injectable biopolymer hydrogels, which exhibit outstanding anticancer effects under the combined irradiation of NIR and ultrasound. In vivo studies using patient-derived xenograft models and tibial osteosarcoma models demonstrate that the hydrogels achieve tumor suppression with efficacy rates of 98.6 % and 67.6 % in the respective models. Furthermore, the hydrogel had good filling and retention capabilities in the bone defect region, which exerted bone repair therapeutic efficacy by polarizing and conveying electrical stimuli to the cells under mild ultrasound radiation. This study provides a comprehensive and clinically feasible strategy for the overall treatment and tissue regeneration of osteosarcoma.

Zwitterion modified cochlear implants resist postoperative infection and inflammation.

The cochlear implant (CI), an advanced electronic device replacing the entire cochlear function, is the ultimate treatment for over 466 million people with disabling hearing loss. Infection after cochlear implantation is a common and worrisome complication despite the routine administration of the antibiotic. The bacterial biofilms formed on the surface of CI are the main cause of antibiotic failure. To solve this problem, we developed a copper-containing zwitterionic coating consisting of anti-adherent poly sulfobetaine methacrylate (PSB) and steadfast polydopamine (PDA). CuSO4/H2O2. was added to accelerate this co-deposition reaction and enhance the anti-bacterial property. The preparation method was simple, rapid, and suitable for clinical use. In our in vitro and in vivo studies, the PSB/PDA(Cu) coating showed high biocompatibility, and conferred CI implants excellent anti-inflammatory, strong anti-bacterial effects, and great anti-biofilm properties to representative Gram-positive and Gram-negative bacteria. These findings implied that the PSB/PDA(Cu) coating was a unique anti-bacterial strategy for enhancing CI performance.

Circulating sNinj1 as a novel predictor of prognosis and severity in hepatocellular carcinoma.

BACKGROUND: The occurrence and development of HCC are closely associated with cell death. Recently, researchers found that Ninj1 plays a pivotal role in PMR during different types of cell death. However, the importance of Ninj1 in HCC has not been extensively investigated. METHODS: This study included 102 newly diagnosed HCC patients and 102 sex and age-matched NCs. Circulating sNinj1 was assessed by ELISA. Serum LDH and IL-1ß were detected through a chemiluminescence assay. The correlations of these biomarkers with disease severity and their potential as prognostic predictors for HCC were evaluated. The dynamic changes of sNinj1, LDH, and IL-1ß levels before and after treatment were recorded. RESULTS: Serum levels of sNinj1, IL-1ß, and LDH were significantly higher in HCC patients. Our study found that the sNinj1 level was positively correlated with tumor size, metastasis, and staging. ROC analysis indicated that the AUC of sNinj1 in differentiating HCC from NCs was 0.85. As a result of tumor thrombosis and invasion of the hepatic vein, sNinj1's AUCs were 0.71 and 0.73, respectively. After partial resection and TACE treatment, serum sNinj1 and LDH exhibited similar change trends. A one-year follow-up analysis also demonstrated that HCC patients with high sNinj1 had significantly poorer survival than those with low sNinj1. CONCLUSIONS: The serum sNinj1 is another diagnostic biomarker supporting the HCC diagnosis. More importantly, it has been shown that circulating sNinj1 reveals potential as a novel predictor of HCC severity and prognosis.

Electro-mechanical coupling directs endothelial activities through intracellular calcium ion deployment.

Conversion between mechanical and electrical cues is usually considered unidirectional in cells with cardiomyocytes being an exception. Here, we discover a material-induced external electric field (Eex) triggers an electro-mechanical coupling feedback loop in cells other than cardiomyocytes, human umbilical vein endothelial cells (HUVECs), by opening their mechanosensitive Piezo1 channels. When HUVECs are cultured on patterned piezoelectric materials, the materials generate Eex (confined at the cellular scale) to polarize intracellular calcium ions ([Ca2+]i), forming a built-in electric field (Ein) opposing Eex. Furthermore, the [Ca2+]i polarization stimulates HUVECs to shrink their cytoskeletons, activating Piezo1 channels to induce influx of extracellular Ca2+ that gradually increases Ein to balance Eex. Such an electro-mechanical coupling feedback loop directs pre-angiogenic activities such as alignment, elongation, and migration of HUVECs. Activated calcium dynamics during the coupling further modulate the downstream angiogenesis-inducing eNOS/NO pathway. These findings lay a foundation for developing new ways of electrical stimulation-based disease treatment.

One-Dimensional Ferroelectric Nanoarrays with Wireless Switchable Static and Dynamic Electrical Stimulation for Selective Regulating Osteogenesis and Antiosteosarcoma.

Preventing local tumor recurrence and simultaneously improving bone-tissue regeneration are in great demand for osteosarcoma therapy. However, the current therapeutic implants fail to selectively suppress tumor growth and enhance osteogenesis, and antitumor therapy may compromise osseointegration of the bone implant. Here, based on the different responses of bone tumor cells and osteoblasts to different electric stimulations, we constructed ferroelectric BaTiO3 nanorod arrays (NBTO) on the surface of titanium implants with switchable dynamic and static electrical stimulation for selective bone-tumor therapy and bone tissue regeneration. Polarized NBTO (PNBTO) generated a sustained dynamic electrical stimulus in response to wireless ultrasonic irradiation ("switch-on"), which disrupted the orientation of the spindle filaments of the tumor cell, blocked the G2/M phase of mitosis, and ultimately led to tumor cell death, whereas it had almost no cytotoxic effect on normal bone cells. Under the switch-off state, PNBTO with a high surface potential provided static electrical stimulation, accelerating osteogenic differentiation of mesenchymal stem cells and enhancing the quality of bone regeneration both in vitro and in vivo. This study broadens the biomedical potential of electrical stimulation therapy and provides a comprehensive and clinically feasible strategy for the overall treatment and tissue regeneration in osteosarcoma.

Space-Confined Synthesis of Thin Polypyrrole Nanosheets in Layered Bismuth Oxychloride for a Photoresponse Antibacterial within the Near-Infrared Window and Accelerated Wound Healing.

Bacterial infection greatly affects the rate of wound healing. Both photothermal and photodynamic antibacterial therapies activated by near-infrared (NIR) light with semiconductor nanomedicine are two effective approaches to address bacterial infections, but they cannot coexist synergistically to kill bacteria more efficiently because of the limitation of the band structure. Here, inspired by the natural core-shell structure and photosynthesis simultaneously, polypyrrole (PPy) is synthesized in the two-dimensional restricted area of the layered bismuth oxychloride (BiOCl) nanosheets through the in situ ultrasonic recombination method. The atomic-level interface contact and bonding formed in the PPy-BiOCl intercalated nanosheets not only improve the light-to-heat conversion capabilities of PPy but also promote the transmission of PPy photogenerated charge carriers to the BiOCl semiconductor. The nanocomposites take advantage of the deeper tissue penetration under NIR light irradiation and exhibit excellent photothermal and photodynamic synergistic antibacterial activity. In addition, PPy-BiOCl intercalated nanosheets have good biocompatibility and accelerate wound healing through their antimicrobial activity and skin repair function. The space-confined synthesis of thin PPy nanosheets in layered structures offers an efficient NIR photoresponsive nanomedicine for the treatment of pathogen infection, with promising applications in infected wound healing.

Plasmon-Enhanced Electrocatalysis of Conductive Polymer-Based Nano-Heterojunction for Small Molecule Metabolites Diagnostics.

Conductive polymers are promising electrode candidates in the nonenzymatic catalytic detection of small molecule metabolites, due to the tunable electronic conductivity and versatile modifiability. However, the complex catalytic reaction pathway of conductive polymers results in lower detection sensitivity and a narrower linear range compared with clinical metal-based and carbon-based electrodes. Localized surface plasmon resonance (LSPR), characterized by deep strong light-matter coupling, has great potential in driving surface catalytic reactions at an ultrafast rate. Here, we constructed a salix argyracea-like polypyrrole nanowires/silver nanoparticles (PPy/AgNPs) heterojunction electrode using polydopamine as a dopant and chelator. Through cyclic voltammetry, the Mott-Schottky curve, and COMSOL simulation, we demonstrated that the LSPR-excited photocarriers enhanced PPy/AgNPs electrode electrocatalysis. Thus, the detection current response and linear range were significantly improved under the LSPR excitation when taking glucose and hydrogen peroxide as models of small molecule metabolites. Furthermore, we discussed the LSPR-enhanced detection mechanism of PPy/AgNPs electrode from the aspects of the Tafel slope, the apparent electron diffusion coefficient, and the charge transfer resistance. This strategy opens a new avenue toward the design of LSPR-enhanced conductive polymer electrodes.

Piezoelectric Hydrogel for Prophylaxis and Early Treatment of Pressure Injuries/Pressure Ulcers.

Pressure injuries/pressure ulcers (PIs/PUs) are a critical global healthcare issue and represent a considerable burden on healthcare resources. Prevention of PIs/PUs is the least costly approach and minimizes the patient suffering compared with treatment. Besides, sustained tissue load alleviation and microenvironment management are the most crucial properties for dressings in PI/PU prevention. Hydrogel dressings have attracted a lot of attention to prevent PIs/PUs because of their unique mechanical properties and ability to manage the microenvironment of skin. However, auxiliary prophylaxis and early treatment of PIs/PUs remain a challenge and an acute clinical demand. Here, we report on an electroactive hydrogel with large stretchability (∼380%) and skinlike ductility, and Young's modulus (0.48 ± 0.03 MPa) matches that of human skin (0.5-1.95 MPa). The hydrogel displayed piezoelectric properties and mechanical-electric response stability and sensitivity. Our results indicated that the hydrogel was able to promote in vitro angiogenesis under piezoelectric stimulation and exhibited biocompatibility, which has the potential for forming fine vessels at the damaged sites of PIs/PUs. Furthermore, finite element analysis and pressure dispersion experiments demonstrated that the hydrogel was suitable for preventing PIs/PUs by redistributing force, reducing tissue distortion, and maintaining the microenvironment for skin. This work offers a new strategy for designing and evaluating the dressing for prophylaxis and the early treatment of PIs/PUs.

Programmable biological state-switching photoelectric nanosheets for the treatment of infected wounds.

Recurrent bacterial infection is a major problem that threatens the tissue repair process. However, most current therapeutic strategies fail to deal with management of the overlap dynamics of bacterial killing and tissue repair. Here, in accord with the different responses of eukaryotic and prokaryotic cells to electric potential, we developed high performance photoelectric BiOCl nanosheets that dynamically switch between conditions that favor either tissue regrowth or antibacterial microenvironments due to light stimulated and bi-modal switching of their surface electrical polarization. In vitro assays demonstrate that, under light illumination, the mannitol modified BiOCl nanosheets show high relative surface potential and achieve robust antibacterial performance. Conversely, under dark conditions, the nanosheets exhibit relatively low surface potential and promote Bone Marrow Stem Cell (BMSCs) proliferation. In vivo studies indicate that BiOCl nanosheets with light switch capabilities promote the significant regeneration of infected skin wounds. This work offers a new insight into treating recurrent bacterial infections with photoelectric biomaterials for light controlled selection of alternative electrical microenvironments, thereby benefiting the capability for either antisepsis or repair of damaged tissues.

Wireless electrical stimulation at the nanoscale interface induces tumor vascular normalization.

Pathological angiogenesis frequently occurs in tumor tissue, limiting the efficiency of chemotherapeutic drug delivery and accelerating tumor progression. However, traditional vascular normalization strategies are not fully effective and limited by the development of resistance. Herein, inspired by the intervention of endogenous bioelectricity in vessel formation, we propose a wireless electrical stimulation therapeutic strategy, capable of breaking bioelectric homeostasis within cells, to achieve tumor vascular normalization. Polarized barium titanate nanoparticles with high mechano-electrical conversion performance were developed, which could generate pulsed open-circuit voltage under low-intensity pulsed ultrasound. We demonstrated that wireless electrical stimulation significantly inhibited endothelial cell migration and differentiation in vitro. Interestingly, we found that the angiogenesis-related eNOS/NO pathway was inhibited, which could be attributed to the destruction of the intracellular calcium ion gradient by wireless electrical stimulation. In vivo tumor-bearing mouse model indicated that wireless electrical stimulation normalized tumor vasculature by optimizing vascular structure, enhancing blood perfusion, reducing vascular leakage, and restoring local oxygenation. Ultimately, the anti-tumor efficacy of combination treatment was 1.8 times that of the single chemotherapeutic drug doxorubicin group. This work provides a wireless electrical stimulation strategy based on the mechano-electrical conversion performance of piezoelectric nanoparticles, which is expected to achieve safe and effective clinical adjuvant treatment of malignant tumors.

Tough and Highly Efficient Underwater Self-Repairing Hydrogels for Soft Electronics.

The vulnerability of hydrogel electronic materials to mechanical damage due to their soft nature has necessitated the development of self-repairing hydrogel electronics. However, the development of such material with underwater self-repairing capability as well as excellent mechanical properties for application in aquatic environments is highly challenging and has not yet been fully realized. This study designs a tough and highly efficient underwater self-repairing supramolecular hydrogel by synergistically combining weak hydrogen bonds (H-bonds) and strong dipole-dipole interactions. The resultant hydrogel has high stretchability (up to 700%) and toughness (4.45 MJ m-3 ), and an almost 100% fast strain self-recovery (10 min). The underwater healing process is rapid and autonomous (98% self-repair efficiency after 1 h of healing). Supramolecular hydrogels can be developed as soft electronic sensors for physiological signal detection (gestures, breathing, microexpression, and vocalization) and real-time underwater communication (Morse code). Importantly, the hydrogel sensor can function underwater after mechanical damage because of its highly efficient underwater self-repairing capability.

Wireless Electrochemotherapy by Selenium-Doped Piezoelectric Biomaterials to Enhance Cancer Cell Apoptosis.

Cancer residues around the surgical site remain a significant cause of treatment failure with cancer recurrence. To prevent cancer recurrence and simultaneously repair surgery-caused defects, it is urgent to develop implantable biomaterials with anticancer ability and good biological activity. In this work, a functionalized implant is successfully fabricated by doping the effective anticancer element selenium (Se) into the potassium-sodium niobate piezoceramic, which realizes the wireless combination of electrotherapy and chemotherapy. Herein, we demonstrate that the Se-doped piezoelectric implant can cause mitochondrial damage by increasing intracellular reactive oxygen species levels and then trigger the caspase-3 pathway to significantly promote apoptosis of osteosarcoma cells in vitro. Meanwhile, its good biocompatibility has been verified. These results are of great importance for future deployment of wireless electro- and chemostimulation to modulate biological process around the defective tissue.

Ultrafast and On-Demand Oil/Water Separation Membrane System Based on Conducting Polymer Nanotip Arrays.

Ultrafast oil/water separation based on tunable superwettability switch remains a big challenge. Here, inspired by the ultrafast water transport mechanism in sarracenia, we develop a micro/nanostructured porous membrane with conducting polymer nanotip arrays through the surface-initiated polymerizations. By modulating the height (ranging from 49-529 nm) and redox states of nanotips, a smart reversible superwettability switch is facile to obtain with contact angles of water/oil arranging from 161° to about 0°. Besides, liquid transport speed was accelerated more than 1.5 times by increasing the nanotip length. The water flux could reach up to 50326 L m-2 h-1 (1000 times that of a typical industrial ultrafiltration membrane). This is attributed to the stable and continuous water film along the nanotips, which provide a lubrication layer, leading to an increase of permeability. This work provides significant insights into macro/nanostructured membrane design for smart separation, blood lipid filtration, and smart nanoreactors with high permeability.

Elastomeric conductive hybrid hydrogels with continuous conductive networks.

Elastomeric conductive hybrid hydrogels (ECHs) combining conducting polymers with elastomeric hydrogels have recently attracted interest due to their wide range of applications in bioelectronics such as wearable or implantable sensing devices. However, the conductivity of ECHs is typically compromised when conductive polymers are used as fillers in hydrogel networks because the inherent limitations of ECHs severely restrict their applicability. Here, we significantly improved the electrical conductivity of ECHs by using a bioinspired catechol derivative, dopamine (DA), as the dopant and mediator for the in situ polymerization of conducting polypyrrole (PPy) within the elastomeric hydrogel dual-networks. In general, ECHs prepared by conventional methods tend to form separate island structures of conductive polymers dispersed within porous hydrogel matrices. We found that a continuous conductive PPy network prepared using the DA mediator facilitated fast electron transfer within the ECHs, which showed good elastomeric mechanical properties, excellent biocompatibility and high force- or strain-responsiveness suitable for implantable strain-sensing applications.

The antibacterial effect of potassium-sodium niobate ceramics based on controlling piezoelectric properties.

The implant infection is one of the most serious postsurgical complications of medical device implantation. Therefore, the development of biocompatible materials with improved antibacterial properties is of great importance. It might be a new insight to apply the intrinsic electrical properties of biomaterials to solve this problem. Here, potassium-sodium niobate piezoceramics (K0.5Na0.5NbO3, KNN) with different piezoelectric constants were prepared, and the microstructures and piezoelectric properties of these piezoceramics were evaluated. Moreover, the antibacterial effect and biocompatibility of these piezoceramics were assayed. Results showed that these piezoceramics were able to decrease the colonies of bacteria staphylococcus aureus (S. aureus), favor the rat bone marrow mesenchymal stem cells (rBMSCs) proliferation and promote the cell adhesion and spreading. The above effects were found closely related to the surface positive charges of the piezoceramics, and the sample bearing the most positive charges on its surface (sample 80KNN) had the best performance in both antibacterial effect and biocompatibility. Based on our work, it is feasible to develop biocompatible antibacterial materials by controlling piezoelectric properties.

A spatially varying charge model for regulating site-selective protein adsorption and cell behaviors.

Implanted materials that enter the body first interact with proteins in body fluids, and cells then perceive and respond to the foreign implant through this layer of adsorbed proteins. Thus, spatially specific regulation of protein adsorption on an implant surface is pivotal for mediating subsequent cellular behaviors. Unlike the surface modulation strategy for traditional biomaterials, in this research, materials with a nonuniform spatial distribution of surface charges were designed to achieve site-selective protein adsorption and further influence cell behavior by charge regulation. Spatially varying microdomains with different levels of piezoelectricity were generated via a focus laser beam-induced phase transition. In addition, after polarization, the zones with different levels of piezoelectricity showed significant differences in surface charge density. The results of scanning Kelvin probe force microscopy (SKPM) showed that the surface charge on the material exhibits a nonuniform spatial distribution after laser irradiation and polarization. Site-specific charge-mediated selective protein adsorption was demonstrated through a protein adsorption experiment. Cell behavior analysis showed that the increase in charge density was conducive to promoting cell adhesion and the formation of filopodia while the nonuniform spatial distribution of charge promoted an oriented arrangement of cells; both features accelerated cell migration. This study provides a new method for spatially regulating protein adsorption through surface charges to further influence cell behaviors.

Soft Conducting Polymer Hydrogels Cross-Linked and Doped by Tannic Acid for Spinal Cord Injury Repair.

Mimicking soft tissue mechanical properties and the high conductivity required for electrical transmission in the native spinal cord is critical in nerve tissue regeneration scaffold designs. However, fabricating scaffolds of high conductivity, tissue-like mechanical properties, and excellent biocompatibility simultaneously remains a great challenge. Here, a soft, highly conductive, biocompatible conducting polymer hydrogel (CPH) based on a plant-derived polyphenol, tannic acid (TA), cross-linking and doping conducting polypyrrole (PPy) chains is developed to explore its therapeutic efficacy after a spinal cord injury (SCI). The developed hydrogels exhibit an excellent electronic conductivity (0.05-0.18 S/cm) and appropriate mechanical properties (0.3-2.2 kPa), which can be achieved by controlling TA concentration. In vitro, a CPH with a higher conductivity accelerated the differentiation of neural stem cells (NSCs) into neurons while suppressing the development of astrocytes. In vivo, with relatively high conductivity, the CPH can activate endogenous NSC neurogenesis in the lesion area, resulting in significant recovery of locomotor function. Overall, our findings evidence that the CPHs without being combined with any other therapeutic agents have stimulated tissue repair following an SCI and thus have important implications for future biomaterial designs for SCI therapy.