Temperature-sensitive Hydrogel Research Articles

Temperature-sensitive semi-IPN composite hydrogels for antibacterial applications

This investigation aims to develop bacterial-resistant temperature-sensitive semi-IPN silver composite hydrogels via a three-step method. Primarily, the temperature-sensitive semi-IPN hydrogels of N-isopropylacrylamide and various concentrations of Pluronic F-127 (PF 127), have been prepared via a free radical polymerization technique. Furthermore, silver ions were encapsulated in the temperature-sensitive semi-IPN hydrogels via the swelling process. Finally, the bacterial-resistant semi-IPN silver composite hydrogels were developed by using an aqueous neem extract as a reducing agent. Semi-IPN hydrogels with higher amount of PF-127 showed a water uptake that was three times better than the pristine poly (N-isopropylacrylamide). The phase transition temperature of the semi-IPN silver composite hydrogels was found to be 34.24 °C, which was confirmed from the swelling and the DSC studies. The resulting hydrogels were characterized by: FTIR, UV–vis, X-ray diffraction, SEM and TEM analyses. The TEM results confirmed the fact that the nanoparticles formed were of spherical shape with a dimension of ˜8 ± 2 nm. The semi-IPN silver-composite hydrogels showed excellent bacteria inhibition against gram-positive bacteria. The results demonstrated that the temperature-sensitive semi-IPN silver-composite hydrogels developed can be employed for clinical applications.

Construction of novel temperature-responsive hydrogel culture system based on the biomimetic method for stem cell sheet harvest

Temperature-responsive hydrogel culture system is considered as an ideal platform for cell sheet harvest, but its complex preparation methods and harsh reaction conditions limit its application. Inspired by the marine mussels, a biomimetic method presented here is to construct a novel temperature-responsive hydrogel culture system for stem cell sheet harvest. The tissue culture polystyrene is first modified with polydopamine coating, and then amine-terminated poly(N-isopropylacrylamide) is grafted onto the coating via the Schiff base or Michael addition reaction to construct the temperature-sensitive hydrogel culture system. Then, bone marrow stromal cells are cultured on the culture system to construct cell sheets. The prepared culture system shows significant temperature-sensitive property with the grafted concentrations of poly(N-isopropylacrylamide) ranging from 0.5 to 1 g/L. Meanwhile, the constructed culture system has low cytotoxicity and facilitates the stem cell adhesion, proliferation, and cell sheet formation at 37°C. When the culture system is placed in a 20°C environment, the cell sheet can be completely detached from the surface of tissue culture polystyrene without being treated with any enzymes. More importantly, the cell morphology, cell sheet thickness, and the fibril structure of the associated proteins are similar to the cells cultured on the tissue culture polystyrene without modification. The biomimetic, simple, inexpensive, and environmentally friendly preparation of the culture system enables it to be used for the harvest of cell sheet and even applied to tissue engineering for tissue regeneration.

Chitosan–Quercetin Bioconjugate as Multi‐Functional Component of Antioxidants and Dual‐Responsive Hydrogel Networks

AbstractMultifunctional hydrogels based on chitosan–quercetin (CHITQ) conjugate are prepared by a thermo‐induced radical procedure in the presence of N‐isopropylacrylamide (NIPAAm), acrylamide (AAm), and N,N′‐methylenebis(acrylamide) (MEBA). At first, quercetin (Q) is grafted onto chitosan backbone with a functionalization degree of 275 mg of Q per gram of conjugate, as calculated by 1H‐NMR analyses to impart antioxidant properties to the polysaccharide. Then, a pH and temperature sensitive hydrogel was obtained by involving CHITQ and NIPAAm in the polymerization reaction. The accessibility of phenolic moieties is modified in response to the hydrogel swelling/deswelling, as confirmed by antioxidant tests performed at different temperatures. Dual stimuli‐responsive hydrogels are proposed for the delivery of caffeine as model drug. The release profiles of caffeine depict a system particularly performing as on/off device at acidic pH with excellent applicability prospects.

Preparation of porous semi-IPN temperature-sensitive hydrogel-supported nZVI and its application in the reduction of nitrophenol

Nanoscale zero-valent iron (nZVI) particles supported on a porous, semi-interpenetrating (semi-IPN), temperature-sensitive composite hydrogel (PNIPAm-PHEMA). nZVI@PNIPAm-PHEMA, was successfully synthesized and characterized by FT-IR, SEM, EDS, XRD and the weighing method. The loading of nZVI was 0.1548 ± 0.0015 g/g and the particle size was 30–100 nm. NZVI was uniformly dispersed on the pore walls inside the PNIPAm-PHEMA. Because of the well-dispersed nZVI, the highly porous structure, and the synergistic effect of PNIPAm-PHEMA, nZVI@PNIPAm-PHEMA showed excellent reductive activity and wide pH applicability. 95% of 4-NP in 100 mL of 400 mg/L 4-NP solution with initial pH 3.0–9.0 could be completely reduced into 4-AP by about 0.0548 g of fresh supported nZVI at 18–25 °C under stirring (110 r/min) within 45 min reaction time. A greater than 99% 4-NP degradation ratio was obtained when the initial pH was 5.0–9.0. The reduction of 4-NP by nZVI@PNIPAm-PHEMA was in agreement with the pseudo-first-order kinetics model with Kobs values of 0.0885–0.101 min−1. NZVI@PNIPAm-PHEMA was able to be recycled, and about 85% degradation ratio of 4-NP was obtained after its sixth reuse cycle. According to the temperature sensitivity of PNIPAm-PHEMA, nZVI@PNIPAm-PHEMA exhibited very good storage stability, and about 88.9% degradation ratio of 4-NP was obtained after its storage for 30 days. The hybrid reducer was highly efficient for the reduction of 2-NP, 3-NP, 2-chloro-4-nitrophenol and 2-chloro-4-nitrophenol. Our results suggest that PNIPAm-PHEMA could be a good potential carrier, with nZVI@PNIPAm-PHEMA having potential value in the application of reductive degradation of nitrophenol pollutants.

Sterilization Procedure for Temperature-Sensitive Hydrogels Loaded with Silver Nanoparticles for Clinical Applications.

Hydrogels (HG) have recognized benefits as drug delivery platforms for biomedical applications. Their high sensitivity to sterilization processes is however one of the greatest challenges regarding their clinical translation. Concerning infection diseases, prevention of post-operatory related infections is crucial to ensure appropriate patient recovery and good clinical outcomes. Silver nanoparticles (AgNPs) have shown good antimicrobial properties but sustained release at the right place is required. Thus, we produced and characterized thermo-sensitive HG based on Pluronic® F127 loaded with AgNPs (HG-AgNPs) and their integrity and functionality after sterilization by dry-heat and autoclave methods were carefully assessed. The quality attributes of HG-AgNPs were seriously affected by dry-heat methods but not by autoclaving methods, which allowed to ensure the required sterility. Also, direct sterilization of the final HG-AgNPs product proved more effective than of the raw material, allowing simpler production procedures in non-sterile conditions. The mechanical properties were assessed in post mortem rat models and the HG-AgNPs were tested for its antimicrobial properties in vitro using extremely drug-resistant (XDR) clinical strains. The produced HG-AgNPs prove to be versatile, easy produced and cost-effective products, with activity against XDR strains and an adequate gelation time and spreadability features and optimal for in situ biomedical applications.

On the blistering of thermo-sensitive hydrogel: the volume phase transition and mechanical instability.

This paper explores the physical mechanisms responsible for the appearance of small blisters on the surface of temperature sensitive hydrogels as they deswell rapidly during their volume phase transition. For this, we develop a numerical model that couples the processes of hydrogel deswelling and blister growth due to the existence of a thin quasi-impermeable layer on its surface. The model points out that blister inflation originates at defects point under the gel's surface, under the effect of the increasing osmotic pressure in the gel as it undergoes its phase transition. Due to their large deformation, these blisters often experience a mechanical instability that triggers a sudden increase in their growth rate at the expense of their closest neighbors. Using a simple computational model, we then show that blisters are able to communicate via internal pressure and that these interactions are mediated by two characteristic time scales related to solvent transport within and between adjacent blisters. Our study finally indicates that these mechanisms can be controlled by temperature and the gel's cross-link density to achieve diversity of blister patterns on the gel's surface. The proposed analysis provides predictions that agree well with experimental observations of NiPAm gels which deswell in various conditions.

Fabrication of Spheroids with Uniform Size by Self-Assembly of a Micro-Scaled Cell Sheet (μCS): The Effect of Cell Contraction on Spheroid Formation.

Cell spheroid culture can be an effective approach for providing an engineered microenvironment similar to an in vivo environment. Our group had recently developed a method for harvesting uniformly sized multicellular spheroids via self-assembly of micro-scaled cell sheets (μCSs) induced by the expansion of temperature-sensitive hydrogels. However, the μCS assembly process was not fully understood. In this study, we investigated the effects of cell number, pattern shape, and contractile force of cells on spheroid formation from micropatterned (width of square pattern from 100-300 μm) hydrogels. We used human dermal fibroblasts (HDFBs) as a model cell type and cultured them for 24 and 72 h. The self-assembly of μCSs cultured on square micropatterns for 72 h rapidly occurred within 4 min after reducing the temperature from 37 to 4 °C. In addition, the size distribution of spheroids was narrower with μCSs from a 72 h culture. Treatment with a ROCK1 inhibitor disrupted cytoskeletal actin fibers and the corresponding μCSs were not detached from the hydrogel. The assembly of the μCS was also affected by the micropattern shape, and the spheroid harvest efficiency was decreased to 60% when using a circular micropattern, which was explained by the stress direction on the circular versus square micropattern upon hydrogel expansion. Therefore, we confirmed that the factors controlling cell-cell interactions are important for spheroid formation using micropatterned hydrogel systems. Finally, the μCSs with dual layers of HDFBs labeled with DiD and DiO dyes resulted in the formation of spheroids with discretely localized colors within the core and shell, respectively, which suggests an outside-in assembly of detached μCSs. In consideration of these complex environmental factors, our system could be utilized in various applications as a three-dimensional culture system to fabricate cell spheroids.

Amino acid functionalized pH- and temperature-sensitive biodegradable injectable hydrogels: synthesis, physicochemical characterization and in vivo degradation kinetics

In recent years, injectable hydrogels that undergo sol-to-gel phase transition in response to the physiological pH- and temperature have attracted increasing attention in therapeutics delivery. In this study, we developed a biodegradable pH- and temperature-sensitive pentablock copolymers by chemical conjugation of L-cysteine oligomer to the backbone of poly(ε-caprolactone-co-lactide)-b-poly(ethylene glycol)-b-poly(ε-caprolactone-co-lactide) (PCLA-PEG-PCLA) copolymers. A series of pentablock copolymers with various chain lengths were prepared by tuning the reaction time and temperature. These copolymers were freely soluble in water at high pH and low temperature; whereas, they could form a stable gel at the physiological condition (pH 7.4, 37 °C). An in vivo injectable study in the back of Sprague-Dawley (SD) rats indicated that the copolymer could form an in situ gel. In addition, an in vivo biodegradation study of the hydrogels showed controlled degradation of the gel matrix without inflammation at the injection site. Overall, our results show that biodegradable pH- and temperature-responsive hydrogel prepared in this study found to be bioresorbable and could be used as a controlled therapeutics delivery vehicle.

Bioinspired sweating with temperature sensitive hydrogel to passively dissipate heat from high-end wearable electronics

Thermal issues limit the application and development of electronic technique. In this work, temperature-sensitive poly (N-isopropylacrylamide) (PNIPA) hydrogel is used to dissipate heat for high-heat-flux thermal management (1555.5 W/m2) of uneven hotspots in virtual reality (VR) device by mimicking the phenomenon of biological sweating. This bioinspired method has an excellent heat dissipation effect, which significantly reduces the temperatures of the VR chips and the external surface. In addition, the heat transfer coefficient produced by hydrogel perspiration is more than twice that of the natural convection and radiation, resulting in a significant increase in cooling effect, and it can operate efficiently even in an environment with a relative humidity of 1. The heat dissipation control mechanism of this cooling method under different heat flux and the key factors under different mechanisms are analyzed. Besides, the hydrogel exhibited excellent stability. After 450 h of high-temperature and high-humidity (90 °C, 85%RH) aging tests and 60 cycles of fatigue tests, hydrogels still maintained a high water content and good swelling properties. The research results suggest that bio-inspired sweat cooling method is an effective and stable thermal management technology for VR devices, which indicates a new approach to address the obstacles of thermal management for development and application of electronic devices and even other heating objects.

Preparation of temperature-sensitive Xanthan/NIPA hydrogel using citric acid as crosslinking agent for bisphenol A adsorption

Hydrogels are emerging materials in pollutant treatment due to their high absorbability and environmental friendliness. Herein, a novel temperature-sensitive hydrogel based on xanthan gum (XG) and N-isopropylacrylamide (NIPA) was successfully synthesized in a water system using low-cost citric acid as crosslinking agent. The lower critical solution temperature of the honeycomb macroporous XG/NIPA hydrogels was 40 °C. Meanwhile, the hydrogels had good water-absorption capacity and the swelling degree reached up to 70.1. Using XG/NIPA hydrogels to absorb bisphenol A (BPA), the maximum adsorption capacity was as high as 458 mg/g. The process was a multilayer adsorption and the rate-controlling step is chemisorption. Thus, the temperature-sensitive XG/NIPA hydrogel had great potential in absorbing BPA from aqueous solutions.

A novel long-sustaining system of apatinib for long-term inhibition of the proliferation of hepatocellular carcinoma cells.

BackgroundApatinib is a newly approved antitumor drug (molecular targeted agent/small molecular kinase inhibitor) for advanced hepatocellular carcinoma (HCC) treatment. However, current oral administration of apatinib could induce the even distribution of drugs in the body and cause the concentration of apatinib in the HCC location to be limited or insufficient. Therefore, it is urgent to develop novel formulations of apatinib to improve its efficiency.Materials and methodsApatinib was prepared to form a stable and even dispersion with cyclodextrin (a clathrate complex/inclusion complex named Apa-Cyc). A temperature-sensitive phase-change hydrogel of apatinib (named Apa-Gel) was prepared using apatinib–cyclodextrin and poloxamer 407. Apa-Gel was injected into HCC tissues in nude mice to examine the long-term antitumor effect.ResultsApa-Gel can transform from liquid to hydrogel at near body temperature and maintain slow release of apatinib in HCC tumor tissues. When injected subcutaneously, one-time administration of Apa-Gel has a long-acting antitumor effect on the subcutaneous growth or epithelial–mesenchymal transition process of HCC cells.ConclusionThis novel slow-releasing system allows apatinib to be released effectively on the long term and facilitates tissue attachment, thereby preserving the efficiency of apatinib over the long term.

Study on the Effect of 1-Butanol Soluble Lignin on Temperature-Sensitive Gel.

A protocol for the fractionation of lignin with 1-butanol as solvent has been proposed in order to improve the utilization of industry alkali lignin. 1-butanol soluble lignin (BSL) was used as a building block for temperature-sensitive hydrogel with N-isopropylacrylamide (NIPAAm) through graft polymerization. The result shows that 1-butanol fractionation is an effective method to improve the molecular weight homogeneity of lignin (PDI, 2.5 to 1.83) and increase the hydroxyl group content (0.585–1.793 mmol/g). The incorporation of BSL into the temperature-sensitive hydrogel can enhance the thermal stability and increase the hydrophobicity of the gel, which leads to a decrease in lower critical solution temperature (LCST). In addition, the compression strength, swelling ratio, and pore size of the gel can be adjusted by the dosage of lignin. This stimuli-responsive gel, with an LCST around 32 °C, is expected to be applied in the agricultural field as a pesticide carrier by stimulating release and absorption properties based on the change in natural environmental temperature.

Hydrogel based biomimetic chameleon fish with super high toughness

Tough hydrogels have unique attributes of high compliance, high toughness, high transparency and excellent biocompatibility. Tough hydrogels have been widely used in the fields of medical devices, flexible electronics, actuators, sensors and soft robotics. This work aims to mimic the function of color change of marine life with extremely soft tissues. PAAM-Alginate tough hydrogel and PNIPAM temperature sensitive hydrogel are synthesized. The composite structures with the two hydrogels are fabricated by 3D printing technique. The designed structure engages with the underwater environment very well and changes color subject to a temperature change. The structure has extremely high toughness and recovers without damage after bending, torsion, impact and indentation. The designed hydrogel composite structure offers new potential to mimic the soft marine livings in the future.

Acousto-thermo-mechanical deformation of hydrogels coupled with chemical diffusion.

We develop an acousto-thermo-mechanical theory for nonlinear (large) deformation of temperature-sensitive hydrogels subjected to temperature and ultrasonic inputs, with diffusion mass transport driven by osmotic pressure accounted for. On the basis of the strain energy due to network stretching, the mixing energy of polymers and small molecules, the Cauchy stress of the deformed hydrogel can be obtained. The acoustic radiation stress generated by the ultrasonic inputs is incorporated into the Cauchy stress to give the constitutive equations of the acousto-thermal-mechanical hydrogel. The mixing energy contains an interaction parameter as a function of temperature and polymer concentration so that hydrogel deformation is temperature dependent. By employing the incompressible condition of polymers and molecules, both the temperature and acoustic radiation stress contribute to osmotic pressure, inducing hydrogel swelling (or shrinking). Specifically, for a temperature-sensitive hydrogel layer immersed in solvent, its acoustic-triggered large deformation is comprehensively analysed under different boundary conditions (e.g. free swelling, uniaxial constraint and biaxial constraint).

Bioinspired pH- and Temperature-Responsive Injectable Adhesive Hydrogels with Polyplexes Promotes Skin Wound Healing.

Despite great potential, the delivery of genetic materials into cells or tissues of interest remains challenging owing to their susceptibility to nuclease degradation, lack of permeability to the cell membrane, and short in vivo half-life, which severely restrict their widespread use in therapeutics. To surmount these shortcomings, we developed a bioinspired in situ-forming pH- and temperature-sensitive injectable hydrogel depot that could control the delivery of DNA-bearing polyplexes for versatile biomedical applications. A series of multiblock copolymer, comprised of water-soluble poly(ethylene glycol) (PEG) and pH- and temperature-responsive poly(sulfamethazine ester urethane) (PSMEU), has been synthesized as in situ-forming injectable hydrogelators. The free-flowing PEG-PSMEU copolymer sols at high pH and room temperature (pH 8.5, 23 °C) were transformed to stable gel at the body condition (pH 7.4, 37 °C). Physical and mechanical properties of hydrogels, including their degradation rate and viscosity, are elegantly controlled by varying the composition of urethane ester units. Subcutaneous administration of free-flowing PEG-PSMEU copolymer sols to the dorsal region of Sprague-Dawley rats instantly formed hydrogel depot. The degradation of the hydrogel depot was slow at the beginning and found to be bioresorbable after two months. Cationic protein or DNA-bearing polyplex-loaded PEG-PSMEU copolymer sols formed stable gel and controlled its release over 10 days in vivo. Owing to the presence of urethane linkages, the PEG-PSMEU possesses excellent adhesion strength to wide range of surfaces including glass, plastic, and fresh organs. More importantly, the hydrogels effectively adhered on human skin and peeled easily without eliciting an inflammatory response. Subcutaneous implantation of PEG-PSMEU copolymer sols effectively sealed the ruptured skin, which accelerated the wound healing process as observed by the skin appendage morphogenesis. The bioinspired in situ-forming pH- and temperature-sensitive injectable adhesive hydrogel may provide a promising platform for myriad biomedical applications as controlled delivery vehicle, adhesive, and tissue regeneration.

Injectable temperature-sensitive hydrogel with VEGF loaded microspheres for vascularization and bone regeneration of femoral head necrosis

The formation of neovascularization inside the bone scaffold could enhance and accelerate the regeneration of large bone defects in femoral head necrosis, the angiogenic growth factors are predominantly expressed during the early phase for a reestablishment of the vascularity. In this paper, the injectable temperature-sensitive star-shaped poly(D,L-lactic-co-glycolic acid)-b-methoxy poly(ethylene glycol) (PLGA-mPEG) block copolymer was developed, during the sol-gel transition process, the vascular endothelial growth factor (VEGF) loaded linear PLGA-mPEG block copolymer microspheres and vascular endothelial cells (VECs) were composited into to form hydrogels. The release of VEGF from hydrogel was delayed compared to that from microspheres. The fluorescent imaging confirmed that VECs had a good proliferation into the hydrogels. The hydrogels were injected into necrosis site of the femoral head, the vessels were observed for 2 weeks, the vessels density and mean vessels diameters increased in next 4–6 weeks, followed by increasing new bone formation. These results suggested that injectable VEGF loaded microspheres/hydrogels composites could be applied for vascularization and bone regeneration of femoral head necrosis.

Subcutaneous Transplantation of MIN6 Beta Cells Embedded in mPEG-Ala Hydrogel

The liver is the current site of choice for clinical islet transplantation, but many intraportal grafts were lost in the early stage of transplantation. Other disadvantages include the difficulty of monitoring the islets and procedure-associated complications. In contrast, the subcutaneous space offers the advantages of a large space, a less invasive procedure and easy graft monitoring and removal. However, islet transplantation into an unmodified subcutaneous site has poor efficacy; possibly due to poor oxygenation and inadequate vascularization of the transplanted tissue. In this study, we tested the feasibility of subcutaneous transplantation of MIN6 beta cells embedded in temperature-sensitive poly(ethylene glycol) methyl ether (mPEG)-Ala hydrogels as scaffolds. After culturing for 14 days, the viability of MIN6 beta cells in mPEG-Ala hydrogel was comparable with those in medium, either assayed by MTT or LIVE/DEAD. Static incubation showed that both had comparable insulin secretion. For in vivo experiments, we infected MIN6 beta cells with luciferase by AAV and then transplanted 5*106 cells embedded in mPEG-Ala hydrogel into the subcutaneous space of each nude mouse’s upper back. Positive In Vivo Imaging System (IVIS) images and positive insulin staining of tissue histology were observed up to 41 days after transplantation. Meanwhile, we incubated MIN6 beta cells with chitosan-coated superparamagnetic iron oxide (CSPIO) overnight and then transplanted 5*106 MIN6 beta cells into the subcutaneous tissue of each nude mouse’s left flank. The graft of CSPIO-labeled MIN6 beta cells was visualized on Magnetic Resonance (MR) scans as distinct hypointense spots on T2-weighted images located at the transplantation site at day 6 and 20. These results indicate that subcutaneous transplantation of MIN6 beta cells embedded in temperature-sensitive mPEG-Ala hydrogels is feasible. Moreover, the IVIS and MR imaging are useful tools for detecting and monitoring beta cells at the subcutaneous site. Disclosure J. Juang: None.H. Lin: None.C. Chen: None.C. Kao: None.S. Wu: None.S. Lin: None.C. Shen: None.J. Wang: None.I. Chu: None.

Fast thermoresponsive optical membrane using hydrogels embedded in macroporous silicon.

We have fabricated a temperature-sensitive hydrogel through copolymerization of N-isopropylacrylamide (NIPAAm) and Acrylamide (AAm) inside a macroporous silicon structure and demonstrated fast thermal response compared to its bulk structure. The presented method allows physical arrangement of micro-sized hydrogels within a predefined arrayed structure. Static and dynamic temperature responses of the fabricated structure are successfully demonstrated through optical transmission measurement. The measured temporal response reveals that presented structure can allow fast response time of the implemented hydrogels. Furthermore, spatial thermo-distribution pattern can be observed through pixel-like, arrayed macropores, which indicates a potential for addressing individual or single-channel hydrogel sensors or actuators through temperature stimulation.

Glow discharge electrolysis plasma initiated synthesis of upconversion luminescent and temperature sensitive multifunctional hydrogel

ABSTRACTIn the present work, a novel multifunctional hydrogel that simultaneously possesses strong upconversion luminescence (UL) and temperature responsibility was fabricated based on the crosslinking of hemicellulose and ricinoleic acid capped NaYF4:Yb/Er in the presence of Poly (N-isopropylacrylamide) (PNIPAM) and polyacrylamide (PAAm) aqueous solution by using glow discharge electrolysis plasma (GDEP) initiated technique. Its structure and properties were characterized by wide angle X-ray diffraction, FT-IR spectra, scanning electron microscopy, transmission electron microscope and fluorescence spectra. The obtained hydrogel exhibited reversibly temperature-dependent UL and highly enhanced sensibility. The luminescence intensity and transmittance of hydrogel showed a sharp decrease in the range of 32–35°C. Furthermore, the luminescence intensity of hydrogel was almost not weakened after five heating-cooling cycles, which may allow their use in remote control thermosensitive switch.

Fabrication of High-Sensitivity Skin-Attachable Temperature Sensors with Bioinspired Microstructured Adhesive.

In this study, we demonstrate the fabrication of a highly sensitive flexible temperature sensor with a bioinspired octopus-mimicking adhesive. A resistor-type temperature sensor consisting of a composite of poly(N-isopropylacrylamide) (pNIPAM)-temperature sensitive hydrogel, poly(3,4-ethylenedioxythiophene) polystyrene sulfonate, and carbon nanotubes exhibits a very high thermal sensitivity of 2.6%·°C-1 between 25 and 40 °C so that the change in skin temperature of 0.5 °C can be accurately detected. At the same time, the polydimethylsiloxane adhesive layer of octopus-mimicking rim structure coated with pNIPAM is fabricated through the formation of a single mold by utilizing undercut phenomenon in photolithography. The fabricated sensor shows stable and reproducible detection of skin temperature under repeated attachment/detachment cycles onto skin without any skin irritation for a long time. This work suggests a high potential application of our skin-attachable temperature sensor to wearable devices for medical and health-care monitoring.