Microbially Inspired Calcium Carbonate Precipitation Pathway Integrated Polyelectrolyte Capsules (MICPC) for Biomolecules Release.

Complexation between oppositely charged polyelectrolytes offers a facile single-step strategy for assembling functional micro-nano carriers for efficient drug and vaccine delivery. However, the stability of the delivery system within the physiological environment is compromised due to the swelling of the polyelectrolyte complex, driven by the charge shielding effect, and consequently leads to uncontrollable burst release, thereby limiting its potential applications. In a pioneering approach, cellular pathway-inspired calcium carbonate precipitation pathways are developed that are integrated into polyelectrolyte capsules (MICPC). These innovative capsules are fabricated at the interface of all-aqueous microfluidic droplets, resulting in a precisely controllable and sustained release profile in physiological conditions. Unlike single-step polyelectrolyte assembly capsules which always perform rapid burst release, the MICPC exhibits a sustainable and tunable release pattern, releasing biomolecules at an average rate of 3-10% per day. Remarkably, the degree of control over MICPC's release kinetics can be finely tuned by adjusting the quantity of synthesized calcium carbonate particles within the polyelectrolyte complex. This groundbreaking work not only deepens the insights into polyelectrolyte complexation but also significantly enhances the overall stability of these complexes, opening up new avenues for expanding the range of applications involving polyelectrolyte complex-related materials.

Intracellular tracking of drug release from pH-sensitive polymeric nanoparticles via FRET for synergistic chemo-photodynamic therapy.

BACKGROUND: Synergistic therapy of tumor is a promising way in curing cancer and in order to achieve effective tumor therapy with real-time drug release monitoring, dynamic cellular imaging and antitumor activity. RESULTS: In this work, a polymeric nanoparticle with Forster resonance energy transfer (FRET) effect and chemo-photodynamic properties was fabricated as the drug vehicle. An amphiphilic polymer of cyclo(RGDfCSH) (cRGD)-poly(ethylene glycol) (PEG)-Poly(L-histidine) (PH)-poly(ε-caprolactone) (PCL)-Protoporphyrin (Por)-acting as both a photosensitizer for photodynamic therapy (PDT) and absorption of acceptor in FRET was synthesized and self-assembled into polymeric nanoparticles with epirubicin (EPI)-acting as an antitumor drug for chemotherapy and fluorescence of donor in FRET. Spherical EPI-loaded nanoparticles with the average size of 150 ± 2.4 nm was procured with negatively charged surface, pH sensitivity and high drug loading content (14.9 ± 1.5%). The cellular uptake of EPI-loaded cRGD-PEG-PH-PCL-Por was monitored in real time by the FRET effect between EPI and cRGD-PEG-PH-PCL-Por. The polymeric nanoparticles combined PDT and chemotherapy showed significant anticancer activity both in vitro (IC50 = 0.47 µg/mL) and better therapeutic efficacy than that of free EPI in vivo. CONCLUSIONS: This work provided a versatile strategy to fabricate nanoassemblies for intracellular tracking of drug release and synergistic chemo-photodynamic therapy.

Emergence of Droplets at the Nonequilibrium All-Aqueous Interface in a Vertical Hele-Shaw Cell.

The interfacial phenomena at liquid-liquid interfaces remain the subject of constant fascination in science and technology. Here, we show that fingers forming at the interface of nonequilibrium all-aqueous systems can spontaneously break into an array of droplets. The dynamic formation of droplets at the water-water (w/w) interface is observed when a less dense aqueous phase, for instance, the dextran solution, is placed on a denser aqueous phase, the polyethylene glycol solution, in a vertical Hele-Shaw cell. Because of the gradual diffusion of water from the upper phase into the lower phase, a dense layer appears at the nonequilibrium w/w interface. As a result, a periodic array of fingers emerge and sink. Remarkably, these fingers break up and an array of droplets are emitted from the interface. We characterize the wavelength of fingering by measuring the average distance between the dominant fingers. By varying the initial concentrations of the two nonequilibrium aqueous phases, we identify experimentally a phase diagram with a wide parameter space in which finger breaking occurs. Finally, plenty of droplets, spontaneously formed when one phase is continuously deposited onto another aqueous phase, further confirm the robustness of our experimental results. Our work suggests a simple yet efficient approach with a potential upscalability to generate all-aqueous droplets.

Partitioning-dependent conversion of polyelectrolyte assemblies in an aqueous two-phase system.

Partitioning refers to the distribution of solute molecules in the two immiscible phases of a mixture of two solutions, such as an aqueous two-phase system (ATPS). The partitioning of RNA and peptide has been adjusted in situ to facilitate their assembly into intracellular membraneless organelles. Despite the immense potential of this approach in artificial systems, a partitioning-dependent assembly of macromolecules has been limited, due to the sophisticated processing associated with their in situ modification. Here we demonstrate an approach to direct the assembly of polyelectrolytes in an ATPS through varying their partitioning via pH changes. Microcapsules can be converted to microgel particles as the polyelectrolytes selectively partition to different emulsion phases when changing pH. Such partitioning-dependence can also be equally applied for complexing hydrophilic nanoparticles with polyelectrolytes in an ATPS. By enabling access of hydrophilic materials across the aqueous interface freely, the ATPS allows modification of their intrinsic properties in situ; this advantage will inspire more versatile control over the partitioning of hydrophilic materials and will create new multi-functional biomaterials.

Microfluidic-based cardiovascular systems for advanced study of atherosclerosis.

Atherosclerosis (AS) is a significant global health concern due to its high morbidity and mortality rates. Extensive efforts have been made to replicate the cardiovascular system and explore the pathogenesis, diagnosis, and treatment of AS. Microfluidics has emerged as a valuable technology for modeling the cardiovascular system and studying AS. Here a brief review of the advances of microfluidic-based cardiovascular systems for AS research is presented. The critical pathogenetic mechanisms of AS investigated by microfluidic-based cardiovascular systems are categorized and reviewed, with a detailed summary of accurate diagnostic methods for detecting biomarkers using microfluidics represented. Furthermore, the review covers the evaluation and screening of AS drugs assisted by microfluidic systems, along with the fabrication of novel drug delivery carriers. Finally, the challenges and future prospects for advancing microfluidic-based cardiovascular systems in AS research are discussed and proposed, particularly regarding new opportunities in multi-disciplinary fundamental research and therapeutic applications for a broader range of disease treatments.

Robust and Wet Adhesive Self-Gelling Powders for Rapid Hemostasis and Efficient Wound Healing.

Healing traumatic wounds is arduous, leaving miscellaneous demands for ideal wound dressings, such as rapid hemostasis, superior wet tissue adhesion, strong mechanical properties, and excellent antibacterial activity. Herein, we report a self-gelling, wet adhesive, stretchable (polyethylenimine/poly(dimethylammonium chloride)/(poly(acrylic acid)/poly(sodium styrenesulfonate)/alkylated chitosan)) ((PEI/PDDA)/(PAA/PSS)/ACS) powder as a new option. The self-gel utilizes noncovalent interactions among in situ formed PDDA/PSS nanoparticles and PEI/PAA polymetric matrices to earn sensational mechanical properties and tensile strength while incorporating ACS to obtain fast hemostasis and therapeutic capacities. The powder can form a hydrogel patch in situ within 3 s upon liquid absorption, capable of resisting pressure higher than twice the blood pressure. Deposition of the self-gelling powders on various wounds, such as rat liver and femoral artery wounds, can stop bleeding in 10 s and lessen the amount of bleeding 6-fold plus in corresponding models. Furthermore, the self-gelling powders can significantly advance the chronic wound healing process by displaying a high wound healing rate and a low inflammatory response and promoting the formation of new blood vessels and tissue regeneration. The satisfactory mechanical properties, strong wet adhesion, sufficient antibacterial properties, ease of usage, adaptability to complex wounds, rapid hemostasis, and superior therapeutic capacities of (PEI/PDDA)/(PAA/PSS)/ACS self-gelling powders render them as a profound wound dressing biomaterial.

All-aqueous microfluidic printing of multifunctional bioactive microfibers promote whole-stage wound healing.

Wound healing involves multi-stages of physiological responses, including hemostasis, inflammation, cell proliferation, and tissue remodeling. Satisfying all demands throughout different stages remains a rarely addressed challenge. Here we introduce an innovative all-aqueous microfluidic printing technique for fabricating multifunctional bioactive microfibers, effectively contributing to all four phases of the healing process. The distinctive feature of the developed microfibers lies in their capacity to be printed in a free-form manner in the aqueous-two phase system (ATPS). This is achieved through interfacial coacervation between alkyl-chitosan and alginate, with enhanced structural integrity facilitated by simultaneous crosslinking with calcium ions and alginate. The all-aqueous printed microfibers exhibit exceptional performance in terms of cell recruitment, blood cell coagulation, and hemostasis. The inclusion of a dodecyl carbon chain and amino groups in alkyl-chitosan imparts remarkable antimicrobial properties by anchoring to bacteria, complemented by potent antibacterial effects of encapsulated silver nanoparticles. Moreover, microfibers can load bioactive drugs like epidermal growth factor (EGF), preserving their activity and enhancing therapeutic effects during cell proliferation and tissue remodeling. With these sequential functions to guide the whole-stage wound healing, this work offers a versatile and robust paradigm for comprehensive wound treatment, holding great potential for optimal healing outcomes.

Thermo-responsive aqueous two-phase system for two-level compartmentalization.

Hierarchical compartmentalization responding to changes in intracellular and extracellular environments is ubiquitous in living eukaryotic cells but remains a formidable task in synthetic systems. Here we report a two-level compartmentalization approach based on a thermo-responsive aqueous two-phase system (TR-ATPS) comprising poly(N-isopropylacrylamide) (PNIPAM) and dextran (DEX). Liquid membraneless compartments enriched in PNIPAM are phase-separated from the continuous DEX solution via liquid-liquid phase separation at 25 °C and shrink dramatically with small second-level compartments generated at the interface, resembling the structure of colloidosome, by increasing the temperature to 35 °C. The TR-ATPS can store biomolecules, program the spatial distribution of enzymes, and accelerate the overall biochemical reaction efficiency by nearly 7-fold. The TR-ATPS inspires on-demand, stimulus-triggered spatiotemporal enrichment of biomolecules via two-level compartmentalization, creating opportunities in synthetic biology and biochemical engineering.

Aqueous-Aqueous Triboelectric Nanogenerators Empowered Multifunctional Wound Healing System with Intensified Current Output for Accelerating Infected Wound Repair.

Triboelectric nanogenerators (TENGs) have emerged as promising devices for generating self-powered therapeutic electrical stimulation over multiple aspects of wound healing. However, the challenge of achieving full 100% contact in conventional TENGs presents a substantial hurdle in the quest for higher current output, which is crucial for further improving healing efficacy. Here, a novel multifunctional wound healing system is presented by integrating the aqueous-aqueous triboelectric nanogenerators (A-A TENGs) with a functionalized conductive hydrogel, aimed at advancing infected wound therapy. The A-A TENGs are founded on a principle of 100% contact interface and efficient post-contact separation of the immiscible interface within the aqueous two-phase system (ATPS), enhancing charge transfer and subsequently increasing current performance. Leveraging this intensified current output, this system demonstrates efficient therapeutic efficacies over infected wounds both in vitro and in vivo, including stimulating fibroblast migration and proliferation, boosting angiogenesis, enhancing collagen deposition, eradicating bacteria, and reducing inflammatory cells. Moreover, the conductive hydrogel ensures the uniformity and integrity of the electric field covering the wound site, and exhibits multiple synergistic therapeutic effects. With the capability to realize accelerated wound healing, the developed "A-A TENGs empowered multifunctional wound healing system" presenting an excellent prospect in clinical wound therapy.

Triboelectric Nanogenerators-Based Therapeutic Electrical Stimulation on Skin: from Fundamentals to Advanced Applications.

Discovery of the amazing and vital therapeutic roles of electrical stimulation (ES) on skin has sparked tremendous efforts to investigate ES suppliers. Among them, triboelectric nanogenerators (TENGs), as a self-sustainable bioelectronic system, can generate self-powered and biocompatible ES for achieving superior therapeutic effects on skin applications. Here, a brief review of the application of TENGs-based ES on skin is presented, with specific discussions of the fundamentals of TENGs-based ES and its feasibility to be applied for adjusting physiological and pathological processes of skin. Then, a comprehensive and in-depth depiction of emerging representative skin applications of TENGs-based ES is categorized and reviewed, with particular descriptions about its therapeutic effects on achieving antibacterial therapy, promoting wound healing, and facilitating transdermal drug delivery. Finally, the challenges and perspectives for further advancing TENGs-based ES toward a more powerful and versatile therapeutic strategy are discussed, particularly regarding opportunities in fundamental multidisciplinary research and biomedical applications.

AIEgen-Conjugated Phase-Separating Peptides Illuminate Intracellular RNA through Coacervation-Induced Emission.

Intrinsically disordered peptides drive dynamic liquid-liquid phase separation (LLPS) in membraneless organelles and encode cellular functions in response to environmental stimuli. Engineering design on phase-separating peptides (PSPs) holds great promise for bioimaging, vaccine delivery, and disease theranostics. However, recombinant PSPs are devoid of robust luminogen or suitable cell permeability required for intracellular applications. Here, we synthesize a peptide-based RNA sensor by covalently connecting tetraphenylethylene (TPE), an aggregation-induced emission luminogen (AIEgens), to tandem peptide repeats of (RRASL)n (n = 1, 2, 3). Interestingly, the conjugation of TPE luminogen promotes liquid-liquid phase separation of the peptide repeats, and the minimum coacervation concentration (MCC) of TPE-(RRASL)n is decreased by an order of magnitude, compared to that of the untagged, TPE-free counterparts. Moreover, the luminescence of TPE-(RRASL)n is enhanced by up to 700-fold with increasing RNA concentration, which is attributed to the constricted rotation of the TPE moiety as a result of peptide/RNA coacervates within the droplet phase. Besides, at concentrations above MCC, TPE-(RRASL)n can efficiently penetrate through human gallbladder carcinoma cells (SGC-996), translocate into the cell nucleus, and colocalize with intracellular RNA. These observations suggest that AIEgen-conjugated PSPs can be used as droplet-based biosensors for intracellular RNA imaging through a regime of coacervation-induced emission.

Zeolitic Imidazolate Framework (ZIF-8) Decorated Iron Oxide Nanoparticles Loaded Doxorubicin Hydrochloride for Osteosarcoma Treatment - in vitro and in vivo Preclinical Studies.

Background: As a broad-spectrum antitumorigenic agent, doxorubicin (DOX) is commonly used as a chemotherapeutic drug for treating osteosarcoma (OS). Still, it is associated with significant cell toxicity and ineffective drug delivery, whereas the zeolite imidazolate framework is extensively applied in the biomedical field as a carrier owing to its favorable biocompatibility, high porosity, and pH-responsiveness. Therefore, we need to develop a drug delivery platform that can effectively increase the antitumorigenic effect of the loaded drug and concurrently minimize drug toxicity. Methods: In this study, a Fe3O4@ZIF-8 nanocomposite carrier was prepared with ZIF-8 as the shell and encapsulated with Fe3O4 by loading DOX to form DOX- Fe3O4@ZIF-8 (DFZ) drug-loaded magnetic nanoparticles. Then, we characterized and analyzed the morphology, particle size, and characteristics of Fe3O4@ZIF-8 and DFZ by TEM, SEM, and Malvern. Moreover, we examined the inhibitory effects of DFZ in vitro and in vivo. Meanwhile, we established a tumor-bearing mouse model, evaluating its tumor-targeting by external magnetic field guidance. Results: DFZ nanoparticles possessed have a size of ~110 nm, with an encapsulation rate of 21% and pH responsiveness. DFZ exerted a superior cytostatic effect and apoptosis rate on K7M2 cells in vitro compared to DOX(p<0.01). In animal experiments, DFZ offers up to 67% tumor inhibition and has shown a superior ability to induce apoptosis than DOX alone in TUNEL results(p<0.01). Tumor-targeting experiments have validated that DFZ can be effectively accumulated in the tumor tissue and enhance anticancer performance. Conclusion: In summary, the DFZ nano-delivery system exhibited a more substantial anti-tumorigenic effect as well as superior active tumor targeting of DOX- Fe3O4@ZIF-8 compared to that of DOX alone in terms of biocompatibility, drug loading capacity, pH-responsiveness, tumor-targeting, and anti-tumorigenic effect, indicating its chemotherapeutic application potential.

Functional nano-systems for transdermal drug delivery and skin therapy.

Transdermal drug delivery is one of the least intrusive and patient-friendly ways for therapeutic agent administration. Recently, functional nano-systems have been demonstrated as one of the most promising strategies to treat skin diseases by improving drug penetration across the skin barrier and achieving therapeutically effective drug concentrations in the target cutaneous tissues. Here, a brief review of functional nano-systems for promoting transdermal drug delivery is presented. The fundamentals of transdermal delivery, including skin biology and penetration routes, are introduced. The characteristics of functional nano-systems for facilitating transdermal drug delivery are elucidated. Moreover, the fabrication of various types of functional transdermal nano-systems is systematically presented. Multiple techniques for evaluating the transdermal capacities of nano-systems are illustrated. Finally, the advances in the applications of functional transdermal nano-systems for treating different skin diseases are summarized.

Bacterial infection microenvironment-responsive porous microspheres by microfluidics for promoting anti-infective therapy.

The overuse of antibiotics for treating bacterial infection has caused severe bacterial resistance and become a public health threat worldwide. It is desired to develop novel antibiotic delivery systems as efficient antibacterial strategies for promoting anti-infective therapy. Herein, the AgNPs-loaded N-[(2-hydroxy-3-trimethyl ammonium) propyl] chitosan (HTCC)/hyaluronic acid (HA) porous microspheres (HHPMs) by microfluidics have been developed as novel bacterial infection microenvironment (IME)-responsive antibiotic delivery systems for promoting antimicrobial therapy. The release of AgNPs can respond explicitly to the IME with acidic pH values and relatively high hyaluronidase concentration. The unique porous structures of HHPMs can effectively facilitate the capture and enrichment of bacteria, thus exerting synergistic antibacterial effects, which can be more efficient in instant bacteria inhibiting and killing. The excellent biocompatibility of HHPMs is revealed by investigating their hemolytic activity and cytotoxicity. In vivo assays demonstrate that the fabricated AgNPs-loaded HHPMs can effectively resist bacterial infection and promote wound healing and tissue regeneration at infected wound sites by inhibition of the bacterial survival. This work indicates that fabricated HHPMs are ideal bacterial infection microenvironment-responsive materials for antibiotic delivery and show great promises for promoting anti-infective therapy in clinics.

Microfluidic-based functional materials: new prospects for wound healing and beyond.

As a popular clinical research topic, the use of functional materials to promote wound healing has attracted significant attention. Microfluidics has been demonstrated as one of the most promising and versatile technologies to fabricate high-performance functional materials contributing to all physiological stages of wound healing. In this respect, we review the state-of-the-art advances in the development of microfluidics for functional material preparation with key applications in wound healing. We first elaborate on the physiological principle of wound healing and the fundamentals of microfluidics. Then we categorize and depict a variety of microfluidic approaches to fabricate functional materials with well-tailored internal structures and integrated functions for wound treatment. We also summarize recent representative microfluidic-based functional materials to facilitate different stages of wound healing. This review concludes with our perspectives on the future directions and challenges in microfluidic investigation of functional wound healing materials, with an emphasize on its versatility in the clinic.

Microfluidic generation of multifunctional core-shell microfibers promote wound healing.

Wound healing is a complex physiological process involving four coordinated stages, including hemostasis, anti-inflammatory, repair, and epithelial formation. Herein, multifunctional core-shell alkylated chitosan/calcium alginate microfibers are fabricated as a novel strategy for promoting wound healing by contributing to each four stages in the entire healing process. Taking advantages of the microfluidic technology, the core-shell microfibers can be generated in a continuous and convenient manner through the interfacial assembly between alkylated chitosan and Na-alginate, as well as the simultaneous crosslink between calcium and the alginate. Generated microfibers possess unique internal structure which can effectively promote the absorption of blood and exudate produced during trauma. Moreover, the dodecyl carbon chain and abundant amino groups of alkylated chitosan provide microfibers with excellent hemostatic and antibacterial properties, which can repair acute hemorrhage and destroy bacteria rapidly. Further, the chronic wound healing process of a skin injury model can be significantly promoted by applying the fabricated microfibers. With these sequential functions to guide the whole-stage wound healing, the presented multifunctional core-shell microfibers create a versatile and robust paradigm for comprehensive wound treatment.

Iodinated cyanine dye-based nanosystem for synergistic phototherapy and hypoxia-activated bioreductive therapy.

Photodynamic therapy (PDT) has been applied in cancer treatment by utilizing reactive oxygen species (ROS) to kill cancer cells. However, the effectiveness of PDT is greatly reduced due to local hypoxia. Hypoxic activated chemotherapy combined with PDT is expected to be a novel strategy to enhance anti-cancer therapy. Herein, a novel liposome (LCT) incorporated with photosensitizer (PS) and bioreductive prodrugs was developed for PDT-activated chemotherapy. In the design, CyI, an iodinated cyanine dye, which could simultaneously generate enhanced ROS and heat than other commonly used cyanine dyes, was loaded into the lipid bilayer; while tirapazamine (TPZ), a hypoxia-activated prodrug was encapsulated in the hydrophilic nucleus. Upon appropriate near-infrared (NIR) irradiation, CyI could simultaneously produce ROS and heat for synergistic PDT and photothermal therapy (PTT), as well as provide fluorescence signals for precise real-time imaging. Meanwhile, the continuous consumption of oxygen would result in a hypoxia microenvironment, further activating TPZ free radicals for chemotherapy, which could induce DNA double-strand breakage and chromosome aberration. Moreover, the prepared LCT could stimulate acute immune response through PDT activation, leading to synergistic PDT/PTT/chemo/immunotherapy to kill cancer cells and reduce tumor metastasis. Both in vitro and in vivo results demonstrated improved anticancer efficacy of LCT compared with traditional PDT or chemotherapy. It is expected that these iodinated cyanine dyes-based liposomes will provide a powerful and versatile theranostic strategy for tumor target phototherapy and PDT-induced chemotherapy.

Efficient epidermal delivery of antibiotics by self-assembled lecithin/chitosan nanoparticles for enhanced therapy on epidermal bacterial infections.

The treatment for epidermal bacterial infections has become a primary healthy concern, producing a significant therapeutic challenge. Here we present a facile strategy to fabricate lecithin/chitosan nanoparticles (LCNPs) for efficient epidermal drug delivery over epidermal bacterial infections. The central rotatable composite design method was used for the optimization of the preparation, and that the optimal size (212.63 ± 1.95 nm) was obtained via analysis of variance (ANOVA). The prepared CIP-LCNPs show an average diameter of 325.9 ± 7.4 nm and a zeta potential of 26.6 ± 1.2 mV. Antibiotics can be well encapsulated in LCNPs and its release kinetics is studied with cumulative release of 93.81 ± 2.05 % for 48 h. The hemolytic activity, cytotoxicity, and skin irritation are further investigated. The zones of inhibition are 2.16 ± 0.04 cm and 2.92 ± 0.03 cm for Escherichia coli and Staphylococcus aureus, respectively. Moreover, in vitro permeation studies demonstrate that LCNPs can increase the accumulation of antibiotics in the epidermis with retention ratio 2-3 fold higher than commercial formulations. The in vivo result over epidermal-infected wound demonstrates the superior therapeutic effects of LCNPs. The developed LCNPs represent an important advance in fabricating therapeutic materials for enhanced therapy over epidermal bacterial infections.

All-Aqueous Microfluidics Fabrication of Multifunctional Bioactive Microcapsules Promotes Wound Healing.

Wound healing involves multiple stages of body responses, including hemostasis, inflammation, cell proliferation, and tissue remodeling. New material design satisfying all demands throughout different stages of wound healing is cherished but rarely discussed. Here we introduce all-aqueous multiphase microfluidics as a novel strategy to fabricate self-assembled, multifunctional alkylated chitosan/alginate microcapsules (SAAMs) as novel therapeutic materials for rapid blood coagulation and wound healing. SAAMs are structurally distinguished by their ultrathin shells with polycationic surface for rapid activation of clotting cascade and their internal porous dextran-rich cores for fast absorption of blood and exudate. These features endow SAAMs with excellent hemostatic properties for acute hemorrhage. Moreover, the alkylated chitosan within the microcapsules exhibits persistent antimicrobial activities against bactericidal infections due to their amphiphilic and cationic surfaces. Besides, cytokines can be safely loaded into the organic-solvent-free microcapsules and released precisely to promote the proliferation of epidermal cells, supporting the subsequent development of granulation tissue and suppression of inflammation in the last stages of wound healing. With the ability to fabricate size-tailored soft microcapsules and to realize time-sequential functions for tissue repairing, the presented "all-aqueous microfluidics generation of multifunctional bioactive SAAMs" create a versatile and robust paradigm for wound treatment.

Liquid-liquid triboelectric nanogenerator based on the immiscible interface of an aqueous two-phase system.

Solid nanogenerators often have limited charge transfer due to their low contact area. Liquid-liquid nanogenerators can transfer a charge better than the solid-solid and solid-liquid counterparts. However, the precise manipulation of the liquid morphology remains a challenge because of the fluidity limits of the liquid. In this work, using the surface tension of a droplet to fix its shape, a liquid-liquid triboelectric nanogenerator in Contact-Separation mode is designed using an immiscible aqueous-aqueous interface, achieving a contact surface charge transfer of 129 nC for a single droplet. The configuration is proven to be applicable in humid environments, and the two-phase materials have good biocompatibility and can be used as an effective drug carrier. Therefore, this nanogenerator is useful for designing future implantable devices. Meanwhile, this design also establishes the foundation of aqueous electronics, and additional applications can be achieved using this route.