Complement C3-Deficiency-Induced Constipation in FVB/N-C3em1Hlee/Korl Knockout Mice Was Significantly Relieved by Uridine and Liriope platyphylla L. Extracts.

Complement component 3 (C3) deficiency has recently been known as a cause of constipation, without studies on the therapeutic efficacy. To evaluate the therapeutic agents against C3-deficiency-induced constipation, improvements in the constipation-related parameters and the associated molecular mechanisms were examined in FVB/N-C3em1Hlee/Korl knockout (C3 KO) mice treated with uridine (Urd) and the aqueous extract of Liriope platyphylla L. (AEtLP) with laxative activity. The stool parameters and gastrointestinal (GI) transit were increased in Urd- and AEtLP-treated C3 KO mice compared with the vehicle (Veh)-treated C3 KO mice. Urd and AEtLP treatment improved the histological structure, junctional complexes of the intestinal epithelial barrier (IEB), mucin secretion ability, and water retention capacity. Also, an improvement in the composition of neuronal cells, the regulation of excitatory function mediated via the 5-hydroxytryptamine (5-HT) receptors and muscarinic acetylcholine receptors (mAChRs), and the regulation of the inhibitory function mediated via the neuronal nitric oxide synthase (nNOS) and inducible NOS (iNOS) were detected in the enteric nervous system (ENS) of Urd- and AEtLP-treated C3 KO mice. Therefore, the results of the present study suggest that C3-deficiency-induced constipation can improve with treatment with Urd and AEtLP via the regulation of the mucin secretion ability, water retention capacity, and ENS function.

Selective ion transport through three-dimensionally interconnected nanopores of quaternized block copolymer membranes for energy harvesting application.

A concentration gradient in an aqueous solution is a promising source of energy that can be converted into electrical energy by an ion-exchange polymer membrane. In concentration-gradient energy harvesters, ion transport through nanoporous channels is an emerging approach to enhance the energy conversion efficiency. Since massive but selective ion transport could be realized through nanochannels, the theoretical calculations predicted that nanoporous membranes can extract significantly larger energy than the conventional non-structured membranes. In this regard, scientists in the field have attempted to produce nanoporous membranes on a macroscopic scale based on 1D, 2D, and 3D materials. However, the fabrication of nanoporous membranes is often accompanied by technical difficulties, which entails high production cost, low throughput, and poor scalability. In this study, we took advantage of the self-segregating properties of block copolymers (BCPs) to address these issues. In particular, the non-solvent-induced phase separation method has been utilized to produce three-dimensionally interconnected nanopores within BCP membranes. In addition, the neutral BCP nanopores' surface was modified with positive charges to allow selective diffusion of anions in concentration-gradient cells. By mounting the porous BCP membranes between two aqueous solutions with different concentrations, we studied the BCP-membrane-mediated energy-harvesting performance.

Comparisons of Extracellular Vesicles from Human Epidural Fat-Derived Mesenchymal Stem Cells and Fibroblast Cells.

Extracellular vesicles (EVs) are generated and secreted by cells into the circulatory system. Stem cell-derived EVs have a therapeutic effect similar to that of stem cells and are considered an alternative method for cell therapy. Accordingly, research on the characteristics of EVs is emerging. EVs were isolated from human epidural fat-derived mesenchymal stem cells (MSCs) and human fibroblast culture media by ultracentrifugation. The characterization of EVs involved the typical evaluation of cluster of differentiation (CD antigens) marker expression by fluorescence-activated cell sorting, size analysis with dynamic laser scattering, and morphology analysis with transmission electron microscopy. Lastly, the secreted levels of cytokines and chemokines in EVs were determined by a cytokine assay. The isolated EVs had a typical size of approximately 30-200 nm, and the surface proteins CD9 and CD81 were expressed on human epidural fat MSCs and human fibroblast cells. The secreted levels of cytokines and chemokines were compared between human epidural fat MSC-derived EVs and human fibroblast-derived EVs. Human epidural fat MSC-derived EVs showed anti-inflammatory effects and promoted macrophage polarization. In this study, we demonstrated for the first time that human epidural fat MSC-derived EVs exhibit inflammatory suppressive potency relative to human fibroblast-derived EVs, which may be useful for the treatment of inflammation-related diseases.

Therapeutic Potential of Mesenchymal Stem Cells (MSCs) and MSC-Derived Extracellular Vesicles for the Treatment of Spinal Cord Injury.

Spinal cord injury (SCI) is a life-threatening condition that leads to permanent disability with partial or complete loss of motor, sensory, and autonomic functions. SCI is usually caused by initial mechanical insult, followed by a cascade of several neuroinflammation and structural changes. For ameliorating the neuroinflammatory cascades, MSC has been regarded as a therapeutic agent. The animal SCI research has demonstrated that MSC can be a valuable therapeutic agent with several growth factors and cytokines that may induce anti-inflammatory and regenerative effects. However, the therapeutic efficacy of MSCs in animal SCI models is inconsistent, and the optimal method of MSCs remains debatable. Moreover, there are several limitations to developing these therapeutic agents for humans. Therefore, identifying novel agents for regenerative medicine is necessary. Extracellular vesicles are a novel source for regenerative medicine; they possess nucleic acids, functional proteins, and bioactive lipids and perform various functions, including damaged tissue repair, immune response regulation, and reduction of inflammation. MSC-derived exosomes have advantages over MSCs, including small dimensions, low immunogenicity, and no need for additional procedures for culture expansion or delivery. Certain studies have demonstrated that MSC-derived extracellular vesicles (EVs), including exosomes, exhibit outstanding chondroprotective and anti-inflammatory effects. Therefore, we reviewed the principles and patho-mechanisms and summarized the research outcomes of MSCs and MSC-derived EVs for SCI, reported to date.

Tunable Chemical Grafting of Three-Dimensional Poly (3, 4-ethylenedioxythiophene)/Poly (4-styrenesulfonate)-Multiwalled Carbon Nanotubes Composite with Faster Charge-Carrier Transport for Enhanced Gas Sensing Performance.

The three-dimensional volumetric application of conductive poly (3,4-ethylenedioxythiophene)/poly (4-styrenesulfonate) (PEDOT:PSS) to multiwalled carbon nanotubes (MWCNTs) has not been widely reported. In this study, the applicability of the 3D PEDOT:PSS-MWCNT composite for a gas sensor was investigated with different PEDOT:PSS concentrations. The gas-sensing performance of the 3D PEDOT:PSS-MWCNT composites was investigated using ethanol and carbon monoxide (CO) gas. Overall, in comparison with the pristine MWCNTs, as the PEDOT:PSS concentration increased, the 3D PEDOT:PSS-MWCNT composites exhibited increased conductivity and enhanced gas sensing performances (fast response and recovery times) to both ethanol and CO gases. Importantly, although the PEDOT:PSS coating layer reduced the number of sites for the adsorption and desorption of gas molecules, the charge-carrier transport between the gas molecules and MWCNTs was significantly enhanced. Thus, PEDOT:PSS can be chemically grafted to MWCNTs to enhance the connectivity and conductivity of a 3D network, leading to possible applications in gas sensors.

Self-Adherent Biodegradable Gelatin-Based Hydrogel Electrodes for Electrocardiography Monitoring.

Patch-type hydrogel electrodes have received increasing attention in biomedical applications due to their high biocompatibility and conformal adherence. However, their poor mechanical properties and non-uniform electrical performance in a large area of the hydrogel electrode should be improved for use in wearable devices for biosignal monitoring. Here, we developed self-adherent, biocompatible hydrogel electrodes composed of biodegradable gelatin and conductive polymers for electrocardiography (ECG) measurement. After incorporating conductive poly(3,4-ethylenedioxythiophene):poly(4-styrenesulfonate) (PEDOT:PSS) into gelatin hydrogels crosslinked by natural crosslinkers (genipin), the mechanical properties and electrical conductivity of the hydrogel electrodes were improved and additionally optimized by adjusting the amounts of crosslinker and PEDOT:PSS, respectively. Furthermore, the effect of dimethyl sulfoxide, as a dopant, on the conductivity of hydrogels was investigated. The gelatin-based, conductive hydrogel patch displayed self-adherence to human skin with an adhesive strength of 0.85 N and achieved conformal contact with less skin irritation compared to conventional electrodes with a chemical adhesive layer. Eyelet-type hydrogel electrodes, which were compatible with conventional ECG measurement instruments, exhibited a comparable performance in 12-lead human ECG measurement with commercial ECG clinical electrodes (3M Red Dot). These self-adherent, biocompatible, gelatin-based hydrogel electrodes could be used for monitoring various biosignals, such as in electromyography and electroencephalography.

α-Linolenic Acid-Enriched Cold-Pressed Perilla Oil Suppress High-Fat Diet-Induced Hepatic Steatosis through Amelioration of the ER Stress-Mediated Autophagy.

Perilla oil has been considered to have excellent potential for treating various diseases due to its contents of beneficial fatty acids, such as α-linolenic acid, oleic acid and linoleic acid. The therapeutic effects and molecular mechanism of an α-linolenic acid-enriched cold-pressed perilla oil (LEP) on hepatic steatosis of an obesity model were investigated by analyzing alterations in fat accumulation and endoplasmic reticulum (ER) stress-mediated autophagy, in high-fat diet (HFD)-induced obesity C57BL/6N mice treated with LEP for 16 weeks. Although no significant alterations were detected in body weight and most organ weights, the liver weight and accumulation of lipid droplets in the liver section were significantly lower in HFD + LEP treated group as compared to the HFD + Vehicle treated group. Reduced mRNA expression levels of adipogenesis and lipogenesis regulating factors, including the peroxisome proliferator-activated receptor (PPAR)γ, CCAAT/enhancer-binding protein (C/EBP)α, fatty acid synthase (FAS), and adipocyte fatty acid-binding protein 2 (aP2) were observed after LEP treatment for 16 weeks, while the levels of lipolysis were remarkably increased in the same group. Moreover, the LEP-treated groups showed suppression of ER stress-regulating factors, such as the C/EBP homologous protein (CHOP), eukaryotic translation initiation factor 2α (eIF2α), inositol-requiring protein 1 (IRE1)α, and Jun-N-terminal kinase (JNK) during anti-hepatic steatosis effects. The expression level of the microtubule-associated protein 1A/1B-light chain 3 (LC3) protein and phosphatidylinositol-3-kinase (PI3K)/AKT/ mammalian target of rapamycin (mTOR) pathway for the autophagy response showed a significant decrease in the HFD+LEP-treated group. Furthermore, ER stress-mediated autophagy was accompanied with enhanced phosphorylation of extracellular signal-regulated kinase (ERK), JNK, and p38 protein in the mitogen-activated protein (MAP) kinase signaling pathway. Taken together, the results of the present study indicate that treatment with LEP inhibits hepatic steatosis in the HFD-induced obese model through regulation of adipogenesis and lipolysis. We believe our results are the first to show that the anti-hepatic steatosis activity of α-linolenic acid from cold-pressed perilla oil might be tightly correlated with the amelioration of ER stress-mediated autophagy.

Metal Ion-Mediated Interliposomal Aggregation of Polydiacetylene Liposomes Incorporating a Phenolic Lipid.

Intercolloidal behaviors mediated by metal-ligand coordination have rarely been studied. In this work, such intercolloidal behaviors were demonstrated visibly using blue-colored polydiacetylene liposomes containing a phenolic lipid that acts as a binding ligand toward metal ions. The optimized liposomes were 150-200 nm in diameter and stable in aqueous solution. In incubation tests with various neocortical metal ions, iron(III) ions produced the most obvious colloidal aggregation of the liposomes. As the pH of the incubation medium was increased from acid to basic, stronger aggregation and increased precipitation behavior were observed. The phenolic lipid is believed to contribute to the interliposomal bridging interaction, and the pH dependence of the complexation between iron(III) and the phenolic lipid inserted in the liposomes were verified.

Pumpless Microflow Cytometry Enabled by Viscosity Modulation and Immunobead Labeling.

Major challenges of miniaturizing flow cytometry include obviating the need for bulky, expensive, and complex pump-based fluidic and laser-based optical systems while retaining the ability to detect target cells based on their unique surface receptors. We addressed these critical challenges by (i) using a viscous liquid additive to control flow rate passively, without external pumping equipment, and (ii) adopting an immunobead assay that can be quantified with a portable fluorescence cell counter based on a blue light-emitting diode. Such novel features enable pumpless microflow cytometry (pFC) analysis by simply dropping a sample solution onto the inlet reservoir of a disposable cell-counting chamber. With our pFC platform, we achieved reliable cell counting over a dynamic range of 9-298 cells/µL. We demonstrated the practical utility of the platform by identifying a type of cancer cell based on CD326, the epithelial cell adhesion molecule. This portable microflow cytometry platform can be applied generally to a range of cell types using immunobeads labeled with specific antibodies, thus making it valuable for cell-based and point-of-care diagnostics.

Listeners' identification and evaluation of Korean idiomatic utterances produced by persons with left- or right-hemisphere damage.

This study investigates the effects of left- (LHD) or right-hemisphere damage (RHD) on the production of matched idiomatic or literal expressions by examining healthy listeners' abilities to identify, evaluate and perceptually characterize the utterances. Native speakers of Korean with LHD or RHD and healthy controls (HCs) produced six ditropically ambiguous (idiomatic or literal) sentences in an elicitation and a repetition task. Healthy listeners identified the sentence types and indicated how well each utterance represented the intended meaning. Perceptual ratings of voice quality were performed by expert listeners. The results indicate a negative effect of RHD on listeners' identification and goodness ratings of utterance type. Repetition yielded better speech exemplars than elicitation. Sentence type was associated with selected voice qualities. These findings support previous reports of prosodic information serving to signal idiomatic versus literal meanings as well as a right-hemisphere involvement in formulaic language and the dual process model of language.

Hyaluronate-Epidermal Growth Factor Conjugate for Skin Wound Healing and Regeneration.

Epidermal growth factor (EGF) has been recognized as an excellent wound healing agent due to its therapeutic function stimulating skin cell growth, proliferation and differentiation. However, the transdermal delivery of EGF poses a significant challenge due to its short half-life and lack of efficient formulation. Here, to improve the transdermal delivery efficiency, EGF was conjugated to hyaluronate (HA), which was formulated into a patch-type film for skin wound healing. HA-EGF conjugate was synthesized by coupling reaction between aldehyde-modified HA and N-terminal amine group of EGF to minimize the loss of biological activities. The HA-EGF conjugates exhibited similar biological activities with native EGF as confirmed by ELISA and proliferation tests using murine and human fibroblasts. For the efficient topical delivery, HA-EGF conjugates were incorporated into a matrix film of high molecular weight HA. Two-photon microscopy clearly visualized more efficient transdermal delivery of HA-EGF conjugates to both normal skin and peripheral tissues around the wound area rather than that of EGF. Optical imaging and ELISA after in vivo transdermal delivery showed that the conjugation of EGF to HA retarded its degradation and extended its residence time in the wound area. Furthermore, in vivo transdermal delivery of HA-EGF conjugate in the patch-type HA film resulted in significantly improved regeneration of skin tissues even into hypodermis.

Sub-100 nm gold nanohole-enhanced Raman scattering on flexible PDMS sheets.

Surface-enhanced Raman spectroscopy (SERS) is a highly sensitive vibrational spectroscopy technique enabling detection of multiple analytes at the molecular level in a nondestructive and rapid manner. In this work, we introduce a new approach to fabricate deep subwavelength-scaled (sub-100 nm) metallic nanohole arrays (quasi-3D metallic nanoholes) on flexible and highly efficient SERS substrates. Target structures have been fabricated using a two-step process consisting of (i) direct pattern transfer of spin-coated polymer films onto polydimethylsiloxane (PDMS) substrates by plasma etching with transferred anodic aluminum oxide masks, and (ii) producing SERS-active substrates by functionalization of the etched polymeric films followed by Au deposition. Such an all-dry, top-down lithographic approach enables on-demand patterning of SERS-active metallic nanoholes with high structural fidelity even onto flexible and stretchable substrates, thus making possible multiple sensing modes in a versatile fashion. For example, metallic nanoholes on flexible PDMS substrates are highly amenable to their integration with curved glass sticks, which can be used in optical fiber-integrated SERS systems. Au surfaces immobilized by probe DNA molecules show a selective enhancement of Raman scattering with Cy5-labeled complementary DNA (as compared to flat Au surfaces), demonstrating the potential of using the quasi-3D Au nanohole arrays for bio-sensing applications.

Microstructured barbs on the North American porcupine quill enable easy tissue penetration and difficult removal.

North American porcupines are well known for their specialized hairs, or quills that feature microscopic backward-facing deployable barbs that are used in self-defense. Herein we show that the natural quill's geometry enables easy penetration and high tissue adhesion where the barbs specifically contribute to adhesion and unexpectedly, dramatically reduce the force required to penetrate tissue. Reduced penetration force is achieved by topography that appears to create stress concentrations along regions of the quill where the cross sectional diameter grows rapidly, facilitating cutting of the tissue. Barbs located near the first geometrical transition zone exhibit the most substantial impact on minimizing the force required for penetration. Barbs at the tip of the quill independently exhibit the greatest impact on tissue adhesion force and the cooperation between barbs in the 0-2 mm and 2-4 mm regions appears critical to enhance tissue adhesion force. The dual functions of barbs were reproduced with replica molded synthetic polyurethane quills. These findings should serve as the basis for the development of bio-inspired devices such as tissue adhesives or needles, trocars, and vascular tunnelers where minimizing the penetration force is important to prevent collateral damage.

Cerebral processing of proper and common nouns: Perception and production following left hemisphere damage.

The goal of this study was to further investigate hemispheric specialization for proper and common nouns by examining the ability of individuals with left hemisphere damage (LHD) to perceive and verbally reproduce famous names and matched common names compared with the performance of matched healthy controls (HC). Ten individuals with LHD due to stroke and 16 age- and education-matched HC completed recognition and production tasks of famous proper and common nouns. All tasks were designed as split-visual field experiments, modelled after the study done by Ohnesorge and Van Lancker. Results contribute to a better understanding of hemispheric roles in perception and production of famous proper nouns, suggesting that (1) both hemispheres can recognize famous proper nouns, possibly due to a right hemisphere role in personal relevance and (2) production of proper nouns as well as common nouns is associated with left hemisphere.

Enhanced Dural Repair Using Biodegradable Sealants Based on Photocurable Hyaluronic Acid.

Cerebrospinal fluid (CSF) leakage is a common complication of intradural surgery or incidental durotomy in neurosurgery. Dural suturing is a common method for durotomy repair, but this technique requires a long operation time and includes the risk of CSF leakage by incomplete sealing. Glue-type sealants are effective for watertight dural closure. However, unresolved shortcomings include insufficient sealing performance, poor biocompatibility, and excessive swelling. Here, a dural sealant using light-activated hyaluronic acid (HA) with multi-networks (HA photosealant) that provides fast sealing performance and high biocompatibility is reported. The HA photosealants form a watertight hydrogel barrier with multilength networks under low-energy visible light exposure (405 nm, <1 J cm-2) for 5 s and allow firm tissue adhesion on the wet dural surface. In a rabbit model of craniectomy and durotomy, HA photosealants exhibit the faster sealing performance of dural tears and enhance dural repair with accelerated bone formation compared to commercial surgical glues, with no degenerative changes, such as inflammation or necrosis, in histopathological evaluation. This biocompatible HA photosealant can be applied in a variety of clinical settings that require fast wound closure as a promising potential.

3D bioprinting of stromal cells-laden artificial cornea based on visible light-crosslinkable bioinks forming multilength networks.

3D bioprinting has the potential for the rapid and precise engineering of hydrogel constructs that can mimic the structural and optical complexity of a healthy cornea. However, the use of existing light-activated bioinks for corneal printing is limited by their poor cytocompatibility, use of cytotoxic photoinitiators (PIs), low photo-crosslinking efficiency, and opaque/colored surface of the printed material. Herein, we report a fast-curable, non-cytotoxic, optically transparent bioprinting system using a new water-soluble benzoyl phosphinate-based PI and photocrosslinkable methacrylated hyaluronic acid (HAMA). Compared with commercially available PIs, the newly developed PI, lithium benzoyl (phenyl) phosphinate (BP), demonstrated increased photoinitiation efficiency under visible light and low cytotoxicity. Using a catalytic amount of BP, the HA-based bioinks quickly formed 3D hydrogel constructs under low-energy visible-light irradiation (405 nm, <1 J cm-2). The mechanical properties and printability of photocurable bioinks were further improved by blending low (10 kDa) and high (100 kDa) molecular weight (MW) HAMA by forming multilength networks. For potential applications as corneal scaffolds, stromal cell-laden dome-shaped constructs were fabricated using MW-blended HAMA/BP bioink and a digital light processing printer. The HA-based photocurable bioinks exhibited good cytocompatibility (80%-95%), fast curing kinetics (<5 s), and excellent optical transparency (>90% in the visible range), potentially making them suitable for corneal tissue engineering.

Antiadhesive Hyaluronic Acid-Based Wound Dressings Promote Wound Healing by Preventing Re-Injury: An In Vivo Investigation.

Wound dressings are widely used to protect wounds and promote healing. The water absorption and antifriction properties of dressings are important for regulating the moisture balance and reducing secondary damages during dressing changes. Herein, we developed a hyaluronic acid (HA)-based foam dressing prepared via the lyophilization of photocrosslinked HA hydrogels with high water absorption and antiadhesion properties. To fabricate the HA-based foam dressing (HA foam), the hydroxyl groups of the HA were modified with methacrylate groups, enabling rapid photocuring. The resulting photocured HA solution was freeze-dried to form a porous structure, enhancing its exudate absorption capacity. Compared with conventional biopolymer-based foam dressings, this HA foam exhibited superior water absorption and antifriction properties. To assess the wound-healing potential of HA foam, animal experiments involving SD rats were conducted. Full-thickness defects measuring 2 × 2 cm2 were created on the skin of 36 rats, divided into four groups with 9 individuals each. The groups were treated with gauze, HA foam, CollaDerm®, and CollaHeal® Plus, respectively. The rats were closely monitored for a period of 24 days. In vivo testing demonstrated that the HA foam facilitated wound healing without causing inflammatory reactions and minimized secondary damages during dressing changes. This research presents a promising biocompatible foam wound dressing based on modified HA, which offers enhanced wound-healing capabilities and improved patient comfort and addresses the challenges associated with conventional dressings.

Nanoporous electroporation needle for localized intracellular delivery in deep tissues.

The exogenous control of intracellular drug delivery has been shown to improve the overall efficacy of therapies by reducing nonspecific off-target toxicity. However, achieving a precise on-demand dosage of a drug in deep tissues with minimal damage is still a challenge. In this study, we report an electric-pulse-driven nanopore-electroporation (nEP) system for the localized intracellular delivery of a model agent in deep tissues. Compared with conventional bulk electroporation, in vitro nEP achieved better transfection efficiency (>60%) with a high cell recovery rate (>95%) under a nontoxic low electroporation condition (40 V). Furthermore, in vivo nEP using a nanopore needle electrode with a side drug-releasing compartment offered better control over the dosage release, time, and location of propidium iodide, which was used as a model agent for intracellular delivery. In a pilot study using experimental animals, the nEP system exhibited two times higher transfection efficiency of propidium iodide in the thigh muscle tissue, while minimizing tissue damage (<20%) compared to that of bulk electroporation. This tissue-penetrating nEP platform can provide localized, safe, and effective intracellular delivery of diverse therapeutics into deep tissues in a controlled manner.

Fast-Embeddable Grooved Microneedles by Shear Actuation for Accurate Transdermal Drug Delivery.

Percutaneous drug delivery using microneedles (MNs) has been extensively exploited to increase the transdermal permeability of therapeutic drugs. However, it is difficult to control the precise dosage with existing MNs and they need to be attached for a long time, so a more simple and scalable method is required for accurate transdermal drug delivery. In this study, we developed grooved MNs that can be embedded into the skin by mechanical fracture following simple shear actuation. Grooved MNs are prepared from hyaluronic acid (HA), which is a highly biocompatible and biodegradable biopolymer. By adjusting the aspect ratio (length:diameter) of the MN and the position of the groove, the MN tip inserted into the skin can be easily broken by shear force. In addition, it was demonstrated that it is possible to deliver the desired amount of triamcinolone acetonide (TCA) for alopecia areata by controlling the position of the groove structure and the concentration of TCA loaded in the MN. It was also confirmed that the tip of the TCA MN can be accurately delivered into the skin with a high probability (98% or more) by fabricating an easy-to-operate applicator to provide adequate shear force. The grooved MN platform has proven to be able to load the desired amount of a drug and deliver it at the correct dose.

Electrically actuatable smart nanoporous membrane for pulsatile drug release.

We report on the fabrication of electrically responsive nanoporous membrane based on polypyrrole doped with dodecylbenzenesulfonate anion (PPy/DBS) that was electropolymerized on the upper part of anodized aluminum oxide membrane. The membrane has regular pore size and very high pore density. Utilizing a large volume change of PPy/DBS depending on electrochemical state, the pore size was acutated electrically. The actuation of the pores was experimentally confirmed by in situ atomic force microscopy and in situ flux measurement. We also demonstrated successfully pulsatile (or on-demand) drug release by using fluorescently labeled protein as a model drug. Because of a fast switching time (less than 10 s) and high flux of the drugs, this membrane could be used for emergency therapy of angina pectoris and migraine, which requires acute and on-demand drug delivery, and hormone-related disease and metabolic syndrome.