ABSTRACT
Diabetic wounds are serious clinical complications which manifest wet condition due to the mass exudate, along with disturbed regulation of inflammation, severe oxidative stress and repetitive bacterial infection. Existing treatments for diabetic wounds remain unsatisfactory due to the lack of ideal dressings that encompass mechanical performance, adherence to moist tissue surfaces, quick repair, and diverse therapeutic benefits. Herein, we fabricated a wet adhesive, self-healing, glucose-responsive drug releasing hydrogel with efficient antimicrobial and pro-healing properties for diabetic wound treatment. PAE hydrogel was constructed with poly(acrylic acid-co-acrylamide) (AA-Am) integrated with a dynamic E-F crosslinker, which consisted of epigallocatechin gallate (EGCG) and 4-(2-acrylamidoethylcarbamoyl)-3-fluorophenylboronic acid (AFPBA). Due to the dynamic crosslinking nature of boronate esters, abundant catechol groups and hydrogen bonding, PAE hydrogel demonstrated excellent mechanical properties with about 1000 % elongation, robust adhesion to moist tissues, fast self-healing, and absorption of biofluids of 10 times of its own weight. Importantly, PAE hydrogel exhibited sustained and glucose-responsive release of EGCG. Together, the bioactive PAE hydrogel had effective antibacterial, antioxidative, and anti-inflammatory properties in vitro, and accelerated diabetic wound healing in rats via reducing tissue-inflammatory response, enhancing angiogenesis, and reprogramming of macrophages. Overall, this versatile hydrogel provides a straightforward solution for the treatment of diabetic wound, and shows potential for other wound-related application scenarios.
ABSTRACT
The olivine-based gallate CaYGaO4 (CYG) with unique cationic ordering, rich lattice sites, and self-photoluminescence (PL) is suitable for application as a host of phosphor. However, research in this area is still in its early stages, especially in high-quality full-spectrum white lighting. Herein, novel CYG: Bi3+/Eu3+ with a controllable PL property is designed based on energy transfer and superposition of emissions from blue self-PL, blue PL of Bi3+, and red-PL of Eu3+. Intriguingly, PL intensity and quantum efficiency could be enhanced via codoping Li+/Zn2+ separately/simultaneously because of their two intentional functions as both charge balancer and flux. Unlike self- and Eu3+ PL, Bi3+ PL is quite sensitive to the lattice environment owing to its exposed 6s2 electronic configuration and is tuned via codoping Sr2+ to regulate the nephelauxetic effect and crystal field splitting concurrently around Bi3+. Meanwhile, for further regulating the PL of Bi3+ and obtaining "warm" white light, La3+ is codoped into the phosphor via crystallographic site engineering to control the substitution trends of Bi3+ at distinct lattice sites. Finally, as a proof-of-concept, a full-spectrum phosphor-converted white-light-emitting diode device under nUV pumping with remarkable color rendering index (Ra), high luminous efficiency, and chemical/thermal stability is achieved by utilizing the individual CYG:Bi/Eu/Li/Zn/Sr/La phosphor via a remote "capping" packaging method.
ABSTRACT
Thrombosis and infection are two major complications associated with central venous catheters (CVCs), which significantly contribute to morbidity and mortality. Antifouling coating strategies currently represent an efficient approach for addressing such complications. However, existing antifouling coatings have limitations in terms of both duration and effectiveness. Herein, we propose a durable zwitterionic polymer armor for catheters. This armor is realized by pre-coating with a robust phenol-polyamine film inspired by insect sclerotization, followed by grafting of poly-2-methacryloyloxyethyl phosphorylcholine (pMPC) via in-situ radical polymerization. The resulting pMPC coating armor exhibits super-hydrophilicity, thereby forming a highly hydrated shell that effectively prevents bacterial adhesion and inhibits the adsorption and activation of fibrinogen and platelets in vitro. In practical applications, the armored catheters significantly reduced inflammation and prevented biofilm formation in a rat subcutaneous infection model, as well as inhibited thrombus formation in a rabbit jugular vein model. Overall, our robust zwitterionic polymer coating presents a promising solution for reducing infections and thrombosis associated with vascular catheters.
ABSTRACT
The gradient modulus in beetle setae plays a critical role in allowing it to stand and walk on natural surfaces. Mimicking beetle setae to create a modulus gradient in microscale, especially in the direction of setae radius, can achieve reliable contact and thus strong adhesion. However, it remains highly challenging to achieve modulus gradient along radial directions in setae-like structures. Here, polydimethylsiloxane (PDMS) micropillar with radial gradient modulus, (termed GM), is successfully constructed by making use of the polymerization inhibitor in the photosensitive resin template. GM gains adhesion up to 84 kPa, which is 2.3 and 4.7 times of soft homogeneous micropillars (SH) and hard homogeneous micropillars (HH), respectively. The radial gradient modulus facilitates contact formation on various surfaces and shifts stress concentration from contact perimeter to the center, resulting in adhesion enhancement. Meanwhile, GM achieves strong friction of 8.1 mN, which is 1.2 and 2.6 times of SH and HH, respectively. Moreover, GM possesses high robustness, maintaining strong adhesion and friction after 400 cycles of tests. The work here not only provides a robust structure for strong adhesion and friction, but also establishes a strategy to create modulus gradient at micron-scale.
ABSTRACT
Blood glucose (BG) monitoring is critical for diabetes management. In recent years, microneedle (MN)-based technology has attracted emerging attention in glucose sensing and detection. In this review, we summarized MN-based sampling for glucose collection and glucose analysis in detail. First, different principles of MN-based biofluid extraction were elaborated, including external negative pressure, capillary force, swelling force and iontophoresis, which would guide the shape design and material optimization of MNs. Second, MNs coupled with different analysis approaches, including Raman methods, colorimetry, fluorescence, and electrochemical sensing, were emphasized to exhibit the trend towards highly integrated wearable sensors. Finally, the future development prospects of MN-based devices were discussed.
Subject(s)
Biosensing Techniques , Wearable Electronic Devices , Glucose , NeedlesABSTRACT
High-quality postoperative rehabilitation is the focus of most patients currently, and hypertrophic scar (HS) greatly reduces the patient's quality of life due to the symptom of severe itching. Traditional HS therapies are associated with limitations, such as poor drug delivery efficiency for topical administration and severe pain for intralesional injection. In this study, we developed a personalized microneedle patch system for minimally invasive and effective treatment of HSs. The microneedle patches were personalized designed and fabricated with 3D printing in order to adapt to individual HS. The optimized microneedle patches were composed of dissolving gelatin and starch and loaded with losartan. Losartan, as a drug class of angiotensin II receptor blockers (ARBs), can effectively inhibit the proliferation and migration of hypertrophic scar fibroblasts (HSFs) and downregulate the gene expression related to scar formation in HSFs. The dissolving microneedle patches exhibited strong mechanical strength, effectively penetrated the stratum corneum of HSs and increased the losartan delivery into HSs upon dissolution of gelatin and starch. Together, the losartan-loaded microneedle patches effectively inhibited the formation of HSs in rabbit ears with reduced scar elevation index (SEI), and decreased fibrosis and collagen deposition in HSs. This personalized microneedle patch system increases the drug delivery efficiency into HSs with minimal invasion, and opens a new window for personalized management and treatment of skin diseases.
Subject(s)
Cicatrix, Hypertrophic , Animals , Rabbits , Cicatrix, Hypertrophic/drug therapy , Angiotensin Receptor Antagonists , Losartan , Gelatin , Quality of Life , Angiotensin-Converting Enzyme Inhibitors , Drug Delivery SystemsABSTRACT
Bioinspired surfaces with special wettabilities attract increasing attention due to their extensive applications in many fields. However, the characterizations of surface wettability by contact angle (CA) and sliding angle (SA) have clear drawbacks. Here, by using an array of triangular micropillars (ATM) prepared by soft lithography, the merits of measuring the friction force of a water droplet on ATM over measurements of CA and SA in characterizing the surface wettability are demonstrated. The CA and SA measurements show ignorable differences in the wettabilities of ATM in opposite directions (1.13%) and that with different periodic parameters under the elongation ranging from 0 to 70%. In contrast, the friction measurement reveals a difference of > 10% in opposite directions. Moreover, the friction force shows a strong dependence on the periodic parameters which is regulated by mechanical stretching. Increasing the elongation from 0 to 50% increases the static and kinetic friction force up to 23.0% and 22.9%, respectively. Moreover, the stick-slip pattern during kinetic friction can reveal the periodic features of the measured surface. The friction force measurement is a sensitive technique that could find applications in the characterization of surface wettabilities.
ABSTRACT
Structural colors from photonic crystals (PCs) have attracted emerging attention in the research area of wearable sensors. Conventional self-assembly of PC takes days to weeks. Here, a fast self-assembly method of PC with horizontal precipitation of silica nanoparticles (NPs) in a polydimethylsiloxane fence, which can be completed within 1-4 h depending on the fence parameters, is introduced. The resultant PC exhibits tunable structural colors in the entire visible spectrum. With infiltration of composite hydrogels containing acrylic acid, acrylamide, chitosan, and carbon nanotubes (CNTs) into the gaps of NPs to form an inverse opal PC, a structural color hydrogel that can quickly respond to different stimuli, including strain and temperature, is obtained. Moreover, with the addition of CNTs, the composite PC hydrogel can also output an electronic signal together with optical color changes. Based on these extraordinary responsive behaviors, the PC hydrogel sensor for quantitative feedback to external stimuli of stretching, bending, pressing, and thermal stimuli, with brilliant color change and electronic signal outputs simultaneously, is demonstrated. This fast-assembled PC hydrogel with excellent responsive properties has great potential for applications in wearable devices, mechanical sensors, temperature sensors, and colorimetric displays.
Subject(s)
Nanotubes, Carbon , Wearable Electronic Devices , Hydrogels/chemistry , Photons , TemperatureABSTRACT
The adhesion behaviors of droplets on surfaces are attracting increasing attention due to their various applications. Many bioinspired superhydrophobic surfaces with different adhesion states have been constructed in order to mimic the functions of natural surfaces such as a lotus leaf, a rose petal, butterfly wings, etc. In this review, we first present a brief introduction to the fundamental theories of the adhesion behaviors of droplets on various surfaces, including low adhesion, high adhesion and anisotropic adhesion states. Then, different techniques to characterize droplet adhesion on these surfaces, including the rotating disk technique, the atomic force microscope cantilever technique, and capillary sensor-based techniques, are described. Wetting behaviors, and the switching between different adhesion states on bioinspired surfaces, are also summarized and discussed. Subsequently, the diverse applications of bioinspired surfaces, including water collection, liquid transport, drag reduction, and oil/water separation, are discussed. Finally, the challenges of using liquid adhesion behaviors on various surfaces, and future applications of these surfaces, are discussed.
Subject(s)
Rosa , Animals , Hydrophobic and Hydrophilic Interactions , Plant Leaves/chemistry , Surface Properties , WettabilityABSTRACT
The design of porous structure in wearable sensors is very important for the detection of mechanical signals. However, it remains challenging to construct a porous structure capable of detecting all kinds of mechanical signals. Here, round wire with long-range orientated micropores (RW-LOM) is fabricated by a newly established freeze printing technique and constructed into a wearable sensor by the incorporation of carbon nanotubes and polydimethylsiloxane. The Sabal leaf-like lamellar structure in RW-LOM is realized and can be tuned by the proper coordination of slurry concentration and the printing parameters. The fine structures in RW-LOM allow the wearable sensor to detect compression, stretching, twisting, and bending with a high sensitivity, stability, and broad detecting range. This work not only provides a wearable sensor with high stability and high sensitivity but also establishes a technique to construct porous wires that could find applications in the fields like intelligent industry and healthcare.
Subject(s)
Nanotubes, Carbon , Wearable Electronic Devices , Nanotubes, Carbon/chemistry , Porosity , Printing, Three-Dimensional , SerenoaABSTRACT
Wound healing is a critical challenge in diabetic patients, mainly due to long-term dysglycemia and its related pathological complications. Subcutaneous insulin injection represents a typical clinical solution, while the low controllability of insulin administration commonly leads to a result far from the optimal therapeutic effect. In this work, we developed a glucose-responsive insulin-releasing hydrogel for microneedle dressing fabrication and then investigated its effects on diabetic wound healing. The hydrogel system was composed of biocompatible gelatin methacrylate (GelMa), glucose-responsive monomer 4-(2-acrylamidoethylcarbamoyl)-3-fluorophenylboronic acid (AFPBA) and gluconic insulin (G-insulin), and the Gel-AFPBA-ins hydrogel-based microneedle dressing was developed by replicating PDMS molds. The resultant hydrogel microneedle dressing exhibited adequate mechanical properties, high biocompatibility, glucose-responsive insulin release behavior upon exposure to different glucose solutions, and potent adhesion to the skin compared to hydrogels without microstructures. The microneedle dressing could accelerate the diabetic wound healing process with decreased inflammatory reaction, enhanced collagen deposition on the regenerated tissue sites, and improved blood glucose control in animals. Therefore, the glucose-responsive insulin-releasing hydrogel microneedle dressing is effective in diabetic wound management and has potential for treatment of other chronic skin injuries.
Subject(s)
Diabetes Mellitus , Hydrogels , Animals , Bandages , Diabetes Mellitus/drug therapy , Glucose , Humans , Hydrogels/chemistry , Hydrogels/pharmacology , Insulin/pharmacology , Insulin/therapeutic use , Wound HealingABSTRACT
The broad applications of 3D-printed poly-ether-ether-ketone (3D-PEEK) structures are largely hampered by their inadequate mechanical properties that can be improved by post treatments. At present, thermal annealing is generally used to improve the mechanical properties of 3D-PEEK. However, it cannot simultaneously improve strength and ductility. Here, a cost-effective postprocessing method is developed to improve the mechanical properties of 3D-PEEK, based on annealing in nonsolvent vapor at room temperature. The annealing in nonsolvent vapor at room temperature simultaneously improves the strength, ductility, and fracture energy of as-printed 3D-PEEK by 22.6%, 151.3%, and 109.1%, respectively. The improved mechanical properties are attributed to enhanced interfacial bonding, increased crystallinity, decreased pinhole defects, and stress relaxation in the 3D-PEEK. Moreover, the annealing in both polar solvents (such as acetone and chloroform) and nonpolar solvents (such as n-hexane) are demonstrated to be effective for improving the mechanical properties of 3D-PEEK. The nonsolvent vapor-annealed 3D-PEEK can thus have potential applications in the fields of medical implants, automotive, aerospace, and more.
Subject(s)
Polyethylene Glycols , Printing, Three-Dimensional , Benzophenones , Ketones/chemistry , Polyethylene Glycols/chemistry , PolymersABSTRACT
Drug delivery with customized combinations of drugs, controllable drug dosage, and on-demand release kinetics is critical for personalized medicine. In this study, inspired by successive opening of layered structures and compartmentalized structures in plants, we designed a multiple compartmentalized capsular structure for controlled drug delivery. The structure was designed as a series of compartments, defined by the gradient thickness of their external walls and internal divisions. Based on the careful choice and optimization of bioinks composed of gelatin, starch, and alginate, the capsular structures were successfully manufactured by fused deposition modeling three-dimensional (3D) printing. The capsules showed fusion and firm contact between printed layers, forming complete structures without significant defects on the external walls and internal joints. Internal cavities with different volumes were achieved for different drug loading as designed. In vitro swelling demonstrated a successive dissolving and opening of external walls of different capsule compartments, allowing successive drug pulses from the capsules, resulting in the sustained release for about 410 min. The drug release was significantly prolonged compared to a single burst release from a traditional capsular design. The bioinspired design and manufacture of multiple compartmentalized capsules enable customized drug release in a controllable fashion with combinations of different drugs, drug doses, and release kinetics, and have potential for use in personalized medicine.
Subject(s)
Capsules , Delayed-Action Preparations , Drug Liberation , Printing, Three-DimensionalABSTRACT
Assessment of lung and heart states is of critical importance for patients with pneumonia. In this study, we present a small-sized and ultrasensitive accelerometer for continuous monitoring of lung and heart sounds to evaluate the lung and heart states of patients. Based on two-stage amplification, which consists of an asymmetric gapped cantilever and a charge amplifier, our accelerometer exhibited an extremely high ratio of sensitivity to noise compared with conventional structures. Our sensor achieves a high sensitivity of 9.2 V/g at frequencies less than 1000 Hz, making it suitable to use to monitor weak physiological signals, including heart and lung sounds. For the first time, lung injury, heart injury, and both lung and heart injuries in discharged pneumonia patients were revealed by our sensor device. Our sound sensor also successfully tracked the recovery course of the discharged pneumonia patients. Over time, the lung and heart states of the patients gradually improved after discharge. Our observations were in good agreement with clinical reports. Compared with conventional medical instruments, our sensor device provides rapid and highly sensitive detection of lung and heart sounds, which greatly helps in the evaluation of lung and heart states of pneumonia patients. This sensor provides a cost-effective alternative approach to the diagnosis and prognosis of pneumonia and has the potential for clinical and home-use health monitoring.
ABSTRACT
Anisotropic topographies and biological cues can simulate the regenerative microenvironment of nerve from physical and biological aspects, which show promising application in nerve regeneration. However, their synergetic influence on injured peripheral nerve is rarely reported. In the present study, we constructed a bionic microenvironment-inspired scaffold integrated with both anisotropic micro-nanocomposite topographies and IKVAV peptide. The results showed that both the topographies and peptide displayed good stability. The scaffolds could effectively induce the orientation growth of Schwann cells and up-regulate the genes and proteins relevant to myelination. Last, three signal pathways including the Wnt/ß-catenin pathway, the extracellular signal-regulated kinase/mitogen-activated protein pathway, and the transforming growth factor-ß pathway were put forward, revealing the main path of synergistic effects of anisotropic micro-nanocomposite topographies and biological cues on neuroregeneration. The present study may supply an important strategy for developing functional of artificial nerve implants.
ABSTRACT
Activation of pro-inflammatory microglia is an important mechanism of the cerebral ischemia-reperfusion (I/R)-induced neuronal injury and dysfunction. Mesenchymal stem cells (MSCs) together with their paracrine factors demonstrated curative potential in immune disorders and inflammatory diseases, as well as in ischemic diseases. However, it remains unclear whether conditioned medium from MSCs could effectively regulate the activation and polarization of microglia exposed to I/R stimulation. In this study, we investigated the effects of conditioned medium from bone marrow MSCs (BMSCs-CM) on I/R-stimulated microglia and the potential mechanism involved, as well as the way to obtain more effective BMSCs-CM. First, cell model of oxygen-glucose deprivation/reoxygenation (OGD/R) was established in microglia to mimic the I/R. BMSCs-CM from different culture conditions (normoxic: 21% O2; hypoxic: 1% O2; hypoxia preconditioning: preconditioning with 1% O2 for 24 h) was used to treat the microglia. Our results showed that BMSCs-CM effectively promoted the survival and alleviated the injury of microglia. Moreover, in microglia exposed to OGD/R, BMSCs-CM inhibited significantly the expression of pro-inflammatory cytokines (TNF-α, IL-1ß, and IL-6), CD86 and inducible nitric oxide synthase, whereas upregulated the levels of anti-inflammatory cytokine (IL-10), CD206 and Arginase-1. These results suggested that BMSCs-CM promoted the polarization of anti-inflammatory microglia. In particular, BMSCs-CM from cultures with hypoxia preconditioning was more effective in alleviating cell injury and promoting anti-inflammatory microglia polarization than BMSCs-CM from normoxic cultures and from hypoxic cultures. Furthermore, inhibition of exosomes secretion could largely mitigate these effects of BMSCs-CM. In conclusion, our results suggested that hypoxia preconditioning of BMSCs could enhance the efficacy of BMSCs-CM in alleviating OGD/R-induced injury and in promoting the anti-inflammatory polarization of microglia, and these beneficial effects of BMSCs-CM owed substantially to exosomes.
Subject(s)
Anti-Inflammatory Agents/metabolism , Cell Polarity , Culture Media, Conditioned/pharmacology , Mesenchymal Stem Cells/pathology , Microglia/pathology , Reperfusion Injury/pathology , Animals , Cell Hypoxia/drug effects , Cell Line , Cell Polarity/drug effects , Cell Survival/drug effects , Exosomes/drug effects , Exosomes/metabolism , Exosomes/ultrastructure , Glucose/deficiency , Male , Mesenchymal Stem Cells/drug effects , Mice , Microglia/drug effects , Mitochondria/drug effects , Mitochondria/pathology , Models, Biological , Neuroprotective Agents/metabolism , Oxygen , Rats, Sprague-Dawley , Reactive Oxygen Species/metabolismABSTRACT
Diabetes and its complications have become crucial public health challenges worldwide. In this study, we aim to develop a dissolving and glucose-responsive insulin-releasing microneedle (MN) patch system, for minimally invasive and glucose-responsive insulin delivery for type 1 diabetes therapy. The MNs were composed of dissolving and biodegradable gelatin and starch materials, which encapsulated glucose-responsive insulin-releasing gold nanocluster (AuNC) nanocarriers. The fabricated MNs had a complete and uniform structure, consisting of an array of 11 × 11 conical needles, with a needle height of 756 µm, a bottom diameter of 356 µm, a tip diameter of 10 µm, and a tip-to-tip distance of 591 µm. The encapsulated AuNC nanocarriers as additives in the MNs enhanced the mechanical strength of the MNs, and facilitated the penetration of the MNs into the skins of mice. Moreover, the AuNC nanocarrier drugs in the MNs enabled MN patches with a glucose-responsive insulin releasing behavior. With one transdermal application of MN patches on the dorsal skin of mice, the MN patches effectively regulated the BG levels of mice in normoglycemic ranges for 1 to 2 days, and effectively alleviated the diabetic symptoms in type 1 diabetic mice. This dissolving and glucose-responsive insulin-releasing MN patch system realized a closed-loop administration of insulin with minimal invasion, providing great potential applications for type 1 diabetes therapy.
Subject(s)
Diabetes Mellitus, Experimental/drug therapy , Diabetes Mellitus, Type 1/drug therapy , Glucose/metabolism , Hypoglycemic Agents/therapeutic use , Insulin/therapeutic use , Administration, Cutaneous , Animals , Diabetes Mellitus, Experimental/chemically induced , Diabetes Mellitus, Experimental/metabolism , Diabetes Mellitus, Type 1/chemically induced , Diabetes Mellitus, Type 1/metabolism , Drug Carriers/chemistry , Gold/chemistry , Hypoglycemic Agents/administration & dosage , Hypoglycemic Agents/chemistry , Insulin/administration & dosage , Metal Nanoparticles/chemistry , Mice , Mice, Inbred C57BL , Needles , Particle Size , Streptozocin , Surface PropertiesABSTRACT
Biosensing is a rising analytical field for detection of biological indicators using transducing systems. Smart materials can response to external stimuli, and translate the stimuli from biological domains into signals that are readable and quantifiable. Smart materials, such as nanomaterials, photonic crystals and hydrogels have been widely used for biosensing purpose. In this review, we illustrate the incorporation of smart materials in biosensing systems, including the design of responsive materials, their responsive mechanism of biosensing, and their applications in detection of four types of common biomolecules (including glucose, nucleic acids, proteins, and enzymes). In the end, we also illustrate the current challenges and prospective of using smart materials in biosensing research fields.
ABSTRACT
Surfaces with tunable liquid adhesion have aroused great attention in past years. However, it remains challenging to endow a surface with the capability of droplet recognition and transportation. Here, a bioinspired surface, termed as TMAS, is presented that is inspired by isotropic lotus leaves and anisotropic butterfly wings. The surface is prepared by simply growing a triangular micropillar array on the pre-stretched thin poly(dimethylsiloxane) (PDMS) film. The regulation of mechanical stress in the PDMS film allows the fine tuning of structural parameters of the micropillar array reversibly, which results in the instantaneous, in situ switching between isotropic and various degrees of anisotropic droplet adhesions, and between strong adhesion and directional sliding of water droplets. TMAS can thus be used for robust droplet transportation and recognition of acids, bases, and their pH strengths. The results here could inspire the design of robust sensor techniques.
ABSTRACT
Recently, microneedle systems have become an attractive solution for drug delivery. Traditionally, microneedle systems were fabricated via template molding methods. In this study, we present a novel method for the fabrication of a microneedle patch system. We used extrusion-based 3D printing and post stretching to fabricate a microneedle patch system for minimally invasive and glucose-responsive insulin delivery for diabetes treatment. First, we investigated the printability of various bioinks composed of alginate with hydroxyapatite as an additive. After printing the substrate and a cylindrical array of the patch, we stretched the top surface of the cylindrical array to form needle-like tips. The prepared microneedle patch contained 6 × 6 microneedles, and only the microneedles performed glucose-responsive release of insulin. Each microneedle was conical in shape, with a base diameter of 601 µm, a tip diameter of 24 µm, and a height of 643 µm. The fabricated microneedles exhibited sufficient mechanical strength to penetrate the skin of mice and responsively released insulin according to the glucose levels both in glucose solution and in type 1 diabetic mice. When transdermal application was performed only once on the skin of mice, the microneedle patches regulated the blood glucose levels of diabetic mice in normoglycemic ranges for up to 40 h and alleviated the diabetic symptoms of the mice. Our study proposed a method for the fabrication of microneedle patch systems, which can be potentially applied for transdermal drug delivery.