PNIPAM Hydrogel Research Articles

Plasmonic Hydrogel Actuators for Octopus-Inspired Photo/Thermoresponsive Smart Adhesive Patch.

Octopuses are notable creatures that can dynamically adhere to a variety of substrates owing to the efficient pressure control within their suction cups. An octopus' suckers are sealed at the rim and function by reducing the pressure inside the cavity, thereby creating a pressure difference between the ambient environment and the inner cavity. Inspired by this mechanism, we developed a plasmonic smart adhesive patch (Plasmonic AdPatch) with switchable adhesion in response to both temperature changes and near-infrared (NIR) light. The AdPatch incorporates an elastic, nanohole-patterned elastomer that mimics the structure of octopus suckers. Additionally, a monolayer of gold nanostars (GNSs) is coated on the patch, facilitating a NIR light-responsive photothermal effect. A musclelike, thermoresponsive poly(N-isopropylacrylamide) (PNIPAM) hydrogel functions as a volumetric actuator to regulate cavity pressure. When exposed to heat or light, the PNIPAM hydrogel shrinks, enabling the AdPatch to achieve strong suction adhesion (134 kPa at 45 °C, 71 kPa at 85 mW cm-2). Owing to its capability to achieve light-triggered remote adhesion without the need for external pressure, the Plasmonic AdPatch can be employed to transfer ultrathin films and biosensors to fragile organs without causing damage.

Smart wireless flexible bandage containing drug loaded polycaprolactone microparticles for real-time monitoring and treatment of chronic wounds.

The quality of life is negatively impacted by chronic wounds for more than 25 million people in the US. They are quite prone to infection, which may lead to the eventual loss of a limb. By exposing the ulcers to treatment agents at the appropriate time, the healing rate is increased. On-demand drug release in a closed-loop system will aid us in reaching our goal. In this study, we have developed a platform capable of real-time diagnosis of bacterial infection by wirelessly reading wound pH, as well as slow and on-demand local administration of antibiotics. The drug carrier microparticles, an electrical patch, a thermoresponsive hydrogel with an integrated microheater, and a flexible pH sensor comprised the closed-loop patch. Here it is reported that slow and smart release of cefazolin can be addressed by incorporation of drug encapsulated hydrophobic microparticles embedded into a thermo-responsive hydrogel. The utilization of a programmable bandage to provide antibiotic medication highlights the need of not only choosing appropriate therapeutic substances but also the controlled release of the medicine and its rate of release within the wound area. The results of our study indicate that the use of cefazolin encapsulated polycaprolactone (PCL) microparticles can effectively regulate the application of antibiotic treatment for chronic skin wounds. The results also showed a substantial gradual release of cefazolin from the thermo-responsive Pnipam hydrogel when the wound dressing was subjected to a temperature of 37°C. We believe that the developed flexible smart bandage can have a significant impact on chronic wound healing.

Colloidal Probe Technique Optimization for Determination of Young's Modulus of Soft Adhesive Hydrogels.

Atomic force microscopy (AFM) is a valuable tool for determining the Young's modulus of a wide range of materials. However, it faces challenges, particularly when assessing adhesive materials like soft poly(N-isopropylacrylamide) (pNIPAM) hydrogels. This study focuses on enhancing the consistency and reliability of AFM measurements by functionally modifying AFM spherical tip cantilevers to address substrate adhesion issues with these hydrogels. Specifically, hydrophobic functionalization with 1H,1H,2H,2H-perfluorooctyltrichlorosilane (PFOCTS) emerged as the most effective approach, yielding consistent and reliable Young's modulus data across various pNIPAM hydrogel samples. This work highlights the importance of optimizing data acquisition in AFM, rather than relying on postprocessing, to reduce inconsistencies in Young's modulus assessment.

Enhancing Temperature Responsiveness of PNIPAM Through 3D‐Printed Hierarchical Porosity

AbstractMaterials with ultra‐fast responsive properties are essential for various applications. Among the responsive materials, poly(N‐isopropylacrylamide) (PNIPAM) stands out due to its well‐studied temperature‐responsive properties. Improving the kinetics of the responsive properties of PNIPAM is, however, still essential for advancing its practical use. Here, the responsive rate of PNIPAM hydrogels is enhanced by first incorporating sub‐micrometer porosity into the material through polymerization‐induced phase separation (PIPS), followed by introducing millimeter scale pores via 3D printing, thereby rendering the material with hierarchical porosity. The 3D‐printed porous PNIPAM structures show accelerated swelling and deswelling, when compared to non‐porous PNIPAM structures, due to enhanced water permeability associated with the continuous network of micrometer to millimeter‐sized pores. Additionally, thinner polymer structures result in faster temperature response rates. At the same time, the mechanical strength of PNIPAM hydrogels with high porosity and thinner polymer walls is not compromised, overcoming the common trade‐off between swelling and mechanical properties.

Mechanical Properties and Material Characterization of Magneto-Thermal Sensitive Hydrogels

When in an alternating magnetic field, magneto-thermal sensitive hydrogels can absorb solvent molecules, causing the gel network to swell several times to its original size. By conducting experiments with magnetic PNIPAm hydrogels (M-PNIPAm), the parameters of the theoretical model for magneto-thermal sensitive hydrogels were experimentally determined. Subsequently, the mechanical behavior of M-PNIPAm hydrogel was studied through finite element analysis and tensile experiments. The numerical calculations based on the thermodynamic model with specific parameters showed consistency with experimental results. The comparison indicated that the proposed theory for magneto-thermal sensitive hydrogels can accurately predict the mechanical property of M-PNIPAm hydrogel, providing theoretical support for investigating large deformation of magneto-thermal sensitive hydrogels. Furthermore, we discovered that the variation of magnetic particle content significantly influence the mechanics properties of hydrogel. Our findings provide valuable insights for the research and application of magneto-thermal sensitive hydrogels.

A light/thermal cascaded-driven equipment for machine recognition inspired by water lilies using as multifunctional soft actuator

Inspired by the natural stimulus–response of plants and animals, a range of soft equipment has been extensively developed and used in intelligent human–computer interaction, editable remote drives, and machine learning. Poly(N-isopropyl acrylamide) (PNIPAM) hydrogels have gained popularity thanks to their low phase transition temperature and excellent flexibility. However, the PNIPAM hydrogels suffer from poor mechanical properties, low electrical conductivity, and lack of self-responsiveness. Herein, a bilayer light/thermal cascaded-driven anisotropic poly acrylamide/poly(N-isopropylacrylamide-co-acrylamide)-polyvinyl alcohol-MXene (P/PP-M) actuator was prepared by a simple two-step polymerization method. The unique bionic light/thermal response mechanism enables rapid conversion of energy forms and the construction of remote editable actuators. Concretely, the mechanical properties of hydrogels (strain: 1014 %, stress: 94 KPa) have been greatly improved by copolymerizing MXene nanosheets and multiplex hydrogels through two-by-two interpenetrating molecular chains. MXene nanosheets formed dynamic networks conferring the hydrogel system with high conductivity and light/thermal conversion efficiency. The P/PP-M soft actuator features high sensitivity (Gauge factor = 3.62), fast response time (400 ms), and cycling durability (>500 cycles). Finally, the energy transfer mechanism from light to thermal energy to kinetic energy was corroborated by preparing a series of bionic equipment. Manual clips were prepared on this basis, which enables the transportation of objects and realizes the real-time reflection of the operating status of remotely driven soft manual clips through changes in electrical signals. Thus, the proposed efficient editable remote-driven machine recognition soft equipment provides new insights for developing intelligent flexible robots and wearable smart devices.

Cartilage-Inspired, High-Strength, and Heat-Tolerant Lubricating Hydrogels by Macrophase Separation.

Hydrogels are considered as a potential cartilage replacement material based on their structure being similar to natural cartilage, which are of great significance in repairing cartilage defects. However, it is difficult for the existing hydrogels to combine the high load bearing and low friction properties (37 °C) of cartilage through sample methods. Herein, we report a facile and new fabrication strategy to construct the PNIPAm/EYL hydrogel by using the macrophase separation of supersaturated N-isopropylacrylamide (NIPAm) monomer solution to promote the formation of liposomes from egg yolk lecithin (EYL) and asymmetric template method. The PNIPAm/EYL hydrogels possess a relatively high compressive strength (more than 12 MPa), fracture energy (9820 J/m2), good fatigue resistance, lubricating properties, and excellent biocompatibility. Compared with the PNIPAm hydrogel, the friction coefficient (COF 0.046) of PNIPAm/EYL hydrogel is reduced by 50%. More importantly, the COF (0.056) of PNIPAm/EYL hydrogel above lower critical solution temperature (LCST) does not increase significantly, exhibiting heat-tolerant lubricity. The finite element analysis further proves that PNIPAm/EYL hydrogel can effectively disperse the applied stress and dissipate energy under load conditions. This work not only provides new insights for the design of high-strength lubricating hydrogels but also lays a foundation for the treatment of cartilage injury as a substitute material.

A ray-inspired flexible robot fish with stable controllability actuated by photo -responsive composite hydrogels with poly(N-isopropylacrylamide) and multi-walled carbon nanotubes

Drawing inspiration from the movement behaviour of rays in nature, we have successfully developed a ray-inspired flexible robot fish driven by visible light. A composite made of poly(N-isopropylacrylamide) (PNIPAM) and multi-walled carbon nanotubes (MWCNTs) has excellent biocompatibility and photo-responsive deformability. The PNIPAM hydrogel flexible material of the robot fish was prepared by light curing printing technology. Under the control of visible light, the robot fish swims in a straight line at an average speed of about 0.42 mm/s. The photoinduced asymmetric deformation mechanism is used to control the deformation of the fins on both sides of the robot fish, so that the robot fish can turn and realize directional swimming control. These findings have important implications for the development of flexible bionic robots and provide valuable insights for the research of bionic robots driven by visible light.

Flexible and thermoresponsive AEMR-pNIPAM/Cs0.33WO3 composite hydrogel film with NIR shielding potential for smart windows and smart curtains

Thermoresponsive flexible smart windows and smart curtains having high near-infrared (NIR) shielding and tuned visible light transmittance are essential for improving the energy efficiency of the buildings. The lower critical solution temperature (LCST) of the cross-linked poly(N-isopropylacrylamide) (pNIPAM) hydrogel film was precisely modified to a desired LCST value at 27.4 °C through the free radical copolymerization with 10 wt% of acrylated epoxidized methyl ricinoleate (AEMR). Cs0.33WO3 as NIR shielding nanoparticles (particle size < 200 nm) were synthesized via high energy ball milling method with AEMR as a surfactant for high NIR shielding efficiency and dispersion—the composite flexible hydrogel films with different wt% (0.3, 0.5,0.7, and 0.9 wt%) of Cs0.33WO3 nanoparticles were fabricated to analyze the NIR shielding efficiency and thermal insulation performance. The copolymeric hydrogel film with 0.7 wt% of Cs0.33WO3 nanoparticles (0.7-CWO) demonstrates a significant reduction in the NIR transmittance (15.0 % to 2.3 %) and variation in visible light transmittance from 73.6 % to 15.7 % while undergoing temperature-induced phase transition. The smart window fabricated with composite hydrogel film exhibits good integral luminous transmittance (Tlum, 380–780 nm, 68.7 %, below LCST) and justifiable solar modulation ability (ΔTsol, 300–2500 nm, 53.6 %). A model house was designed to monitor the indoor temperature difference, and a noticeable variation of 7 °C was observed in the house with and without 0.7-CWO film. Further, the developed composite material showed improvement in flexibility, water resistance, and thermal stability, confirming its usage for energy-saving smart windows or smart curtains.

Adaptable intelligent filters based on nanotextured nonwoven membranes containing water-insoluble hydrogels

The work demonstrates, for the first time, thermo-responsive, water-insoluble, hydrogel-based, nano-fibrous filter media comprised of copolymers of N-isopropylacrylamide (NIPAM) and methyl methacrylate formed by electrospinning. Moreover, a comprehensive novel physical explanation of all aspects responsible for the physical mechanisms resulting in the thermo-responsive regulation of the water flow rate and an enhanced interception of nanoparticles by such filter membranes is given. They are the wettable-non-wettable transition, pore, and fiber-size changes, as well as a diminishing filter thickness at the lower critical solution temperature (LCST) of the copolymers developed here, which interplay with a significant reduction in the water viscosity with temperature. Poly(N-isopropylacrylamide) (PNIPAM) hydrogel is an attractive material because of its thermo-responsive properties. Its wettability changes with water temperature. This characteristic holds great promise for the development of advanced filter media and related responsive materials. In this study, PNIPAM hydrogels were designed and transformed into filter membranes for applications in water filtration in biomedical and other related systems. These thermo-responsive filter membranes offer the potential for enhanced filtration efficiency, selectivity, and the overall system performance. Here, two different procedures were adopted to form water-insoluble thermo-responsive filter media based on PNIPAM hydrogels. The PNIPAM-based hydrogels were electrospun, resulting in the formation of thermo-responsive water-insoluble nanofiber membranes. These membranes underwent a series of comprehensive experiments to assess their performance and characteristics, including mass loss, water droplets for the wettability assessment, filtration tests, shrinkage measurements, and microscopic observations. These diverse experiments yield a full understanding of the PNIPAM-based nanofiber membranes’ properties and their potential applications.

Atomistic insights into the mechanical properties of cross-linked Poly(N-isopropylacrylamide) hydrogel

Poly(N-isopropylacrylamide) (PNIPAM) is a highly versatile thermo-responsive hydrogel with immense potential for applications in biomedicine and tissue engineering. While PNIPAM has been extensively researched, there remains a significant gap in understanding its mechanical behavior at the atomistic scale. To address this challenge, this study employs molecular dynamics (MD) simulations to delve into the mechanical response of cross-linked PNIPAM hydrogels. The uniqueness of this research lies in our emphasis on providing atomic-level insights into the influence of chemical cross-linking and physical entanglements, as well as quantifying their effects during the application of strain. This represents a novel contribution to the study of hydrogels. MD simulations enable us to scrutinize the behavior of individual polymer chains and their intricate interactions in unprecedented detail, shedding light on microscale phenomena that are often inaccessible through experiments alone. To tackle the complexities associated with atomistic simulations of cross-linked hydrogels, we introduce a dynamic cross-linking algorithm. This innovative approach incorporates a nonreactive force field to construct realistic three-dimensional hydrogel microstructures, employing a stepwise bond formation strategy. Our findings underscore the remarkable impact of increasing the Degree of Cross-linking (DoC) and/or the Degree of Polymerization (DoP) on enhancing the robustness and elastic modulus of PNIPAM hydrogels. Additionally, we uncover the stochastic nature of chemical cross-linking, leading to the formation of anisotropic super-fragments when DoC exceeds a critical threshold. Furthermore, this research highlights the pivotal role of low strain rates on the order of 106 s−1 in accurately modeling the mechanical properties of hydrogels using MD simulations. This approach enables us to obtain meaningful quantitative mechanical properties that align with experimental results reported in the existing literature. In summary, this paper offers an unprecedented level of insight into the intricate interplay of chemical cross-linking and physical entanglements, providing a foundation for future research in this domain.

Photothermally responsive and durable polydopamine-modified MXene-PNIPAM hydrogels for smart friction regulation

In this study, a polydopamine (PDA)-modified MXene-PNIPAM (pMP) hydrogel is prepared using a soap-free emulsion polymerization method, which shows enhanced anti-oxidative, photo-thermal, and tribological properties. The introduction of PDA not only inhibits the oxidation of MXene but also enhances the photo-thermal conversion efficiency of the hydrogel. Even after 50 days, it can still maintain good photo-thermal conversion performance. Moreover, compared with PNIPAM hydrogel, the friction coefficient (COF) and wear volume of pMP hydrogel as lubricant were reduced by 33% and 85%, respectively. Interestingly, the control of COF with excellent reversibility and durability is achieved using pMP hydrogel modulated by near-infrared light. The pMP composite hydrogel exhibits promising prospects in the fields of intelligent robots and biomedical devices.

Microgel-Crosslinked Thermo-Responsive Hydrogel Actuators with High Mechanical Properties and Rapid Response.

Smart hydrogels responsive to external stimuli are promising for various applications such as soft robotics and smart devices. High mechanical strength and fast response rate are particularly important for the construction of hydrogel actuators. Herein, tough hydrogels with rapid response rates are synthesized using vinyl-functionalized poly(N-isopropylacrylamide) (PNIPAM) microgels as macro-crosslinkers and N-isopropylacrylamide as monomers. The compression strength of the obtained PNIPAM hydrogels is up to 7.13MPa. The response rate of the microgel-crosslinked hydrogels is significantly enhanced compared with conventional chemically crosslinked PNIPAM hydrogels. The mechanical strength and response rate of hydrogels can be adjusted by varying the proportion of monomers and crosslinkers. The lower critical solution temperature (LCST) of the PNIPAM hydrogels could be tuned by copolymerizing with ionic monomer sodium methacrylate. Thermo-responsive bilayer hydrogels are fabricated using PINPAM hydrogels with different LCSTs via a layer-by-layer method. The thermo-responsive fast swelling and shrinking properties of the two layers endow the bilayer hydrogel with anisotropic structures and asymmetric response characteristics, allowing the hydrogel to respond rapidly. The bilayer hydrogels are fabricated into clamps to grab small objects and flowers that mimicked the closure of petals, and it shows great application prospects in the field of actuators.

A highly conductive, robust, self-healable, and thermally responsive liquid metal-based hydrogel for reversible electrical switches.

This study introduces a thermally responsive smart hydrogel with enhanced electrical properties achieved through volume switching. This advancement was realized by incorporating multiscale liquid metal particles (LMPs) into the PNIPAM hydrogel during polymerization, using their inherent elasticity and conductivity when deswelled. Unlike traditional conductive additives, LMPs endow the PNIPAM hydrogel with a remarkably consistent volume switching ratio, significantly enhancing electrical switching. This is attributed to the minimal nucleation effect of LMPs during polymerization and their liquid-like behavior, like vacancies in the polymeric hydrogel under compression. The PNIPAM/LMP hydrogel exhibits the highest electrical switching, with an unprecedented switch of 6.1 orders of magnitude. Even after repeated swelling/deswelling cycles that merge some LMPs and increase the conductivity when swelled, the hydrogel consistently maintains an electrical switch exceeding 4.5 orders of magnitude, which is still the highest record to date. Comprehensive measurements reveal that the hydrogel possesses robust mechanical properties, a tissue-like compression modulus, biocompatibility, and self-healing capabilities. These features make the PNIPAM/LMP hydrogel an ideal candidate for long-term implantable bioelectronics, offering a solution to the mechanical mismatch with dynamic human tissues.

Bidirectional optical response hydrogel with adjustable human comfort temperature for smart windows.

Smart windows are effective in reducing the energy consumption of air conditioning and lighting systems, while contributing to maintaining the comfort zone of temperature in the indoor environment. Currently used smart windows mainly rely on traditional single-phase thermochromic material in which only one abrupt optical change occurs during temperature changes, and their inherent characteristics may not be suited for a practical balance of energy saving and privacy protection. Here, we developed a novel bidirectional optically responsive smart window (BSW) with unique bidirectional optical response features by introducing sodium dodecyl sulfate (SDS)/potassium tartrate (PTH) micelles into PNIPAM hydrogel to form a composite hydrogel, which was encapsulated in two glass panels. The upper critical solution temperature (UCST) and lowest critical solution temperature (LCST) of the material can be individually adjusted and are capable of matching the human comfort zone of temperature. In addition, the smart window exhibits remarkable transparency (92.5%), visible light transmission ratio (Tlum = 91.31%), and excellent solar modulation (ΔTsol,UCST = 76.34%, ΔTsol,LCST = 76.75%). Moreover, it possesses selectivity in transmitting light in the infrared band of solar radiation and can complete the "transparent-opaque" transition in a very narrow temperature range (<1 °C). When at comfortable temperatures, the highly transparent smart windows facilitate interior light and appreciation of the view. At low temperatures, SDS/PTH micelles aggregate to form large micelles, blocking the transmission of light and protecting customer privacy. At high temperatures, PNIPAM can undergo a "sol-gel" transition, thus blocking incident solar radiation. Taken together, these proposed materials with bidirectional optical response characteristics would be harnessed as a promising platform for building energy conservation, anti-counterfeiting, information encryption, and temperature monitoring.

4D Printing Nanocomposite Hydrogel Based on PNIPAM and Prussian Blue Nanoparticles Using Stereolithography

AbstractThe potential of photoactive Prussian blue nanoparticles dispersed in thermo‐responsive PNIPAM hydrogels in 4D printing using a stereolithography is investigated with digital light processing. The proportion of Prussian blue nanoparticles used in the resin is chosen to deliver a significant photothermal effect providing a heating above the volume phase transition temperature of the final nanocomposite hydrogels; while, giving only a limited effect on light scattering during the 3D printing process. Four formulations with various amounts of Prussian blue nanoparticles are used to print 3D structures with different shapes, such as Aztec pyramids, cylinders, gyroid porous cubes, and porous films. The shrinkage effect triggered by light irradiation at 808 nm on the as‐obtained nanocomposite hydrogels is demonstrated through the delivery of a representative molecule fluorescein and a triggered 4D shape‐morphing effect.

Kinetics of Light-Responsive CNT / PNIPAM Hydrogel Microactuators.

Light-responsive microactuators composed of vertically aligned carbon nanotube (CNT) forests mixed with poly(N-isopropylacrylamide) (PNIPAM) hydrogel composites are studied. The benefit of this composite is that CNTs act as a black absorber to efficiently capture radiative heating and trigger PNIPAM contraction. In addition, CNT forests can be patterned accurately using lithography to span structures ranging from a few micrometers to several millimeters in size, and these CNT-PNIPAM composites can achieve response times as fast as 15ms. The kinetics of these microactuators are investigated through detailed analysis of high-speed videos. These are compared to a theoretical model for the deswelling dynamics, which combines thermal convection and polymer diffusion, and shows that polymer diffusion is the rate-limiting factor in this system. Applications of such CNT/hydrogel actuators as microswimmers are discussed, with light-actuating micro-jellyfish designs exemplified, and >1500 cycles demonstrated.

The thermochromic smart window and thermo-electrochromic device(T-ECD) based on PNIPAm/Ppy composite hydrogel for fast phase transition

Thermochromic smart windows possess great application potential in terms of building energy conservation. Herein, a novel smart window is designed by combining thermochromic poly(N-isopropylacrylamide) (PNIPAm) and polypyrrole (Ppy). The photothermal conversion effect of Ppy could effectively accelerate the phase transition of PNIPAm. The Ppy could provide extra heat for PNIPAm hydrogel, the phase transition time of PNIPAm/Ppy would be reduced to 3 min(12 min for pure PNIPAm hydrogel). The smart window exhibits excellent solar modulation efficiency(53.7 %). Different concentrations of KCl could regulate phase transition temperature of PNIPAm between 20 and 32 °C. Under irradiation of simulated light for 20 min, the water temperature of test tube covered by PNIPAm/Ppy smart window is 3.5 °C lower than that of blank glass. Moreover, T-ECD based on PNIPAm/Ppy could reduce phase transition time to 90 s. The electrochromic property of Ppy could endow T-ECD with more colours, and The T-ECD exhibits high solar modulation efficiency(63.0 %) which could decline transmittance to 0.2 %. PNIPAm/Ppy composite hydrogel provides new ideas for the design of thermochromic smart windows and thermo-electrochromic dual-response devices.

Artificial Skin with Patterned Stripes for Color Camouflage and Thermoregulation.

Chameleons are famous for their quick color changing abilities, and it is commonly assumed that they do this for camouflage. However, recent reports revealed that chameleons also change color for body temperature regulation. Inspired by the structure of the panther chameleon's skin, a stripe-patterned poly(N-isopropylacrylamide) (PNIPAM) and polyacrylamide (PAM) hydrogel film with a laminated structure is fabricated in this work; thus, both camouflage and thermoregulation can be achieved through controlling Vis and NIR light effectively. For the PNIPAM stripe, the upper layer is the native PNIPAM hydrogel and the lower layer is the carbon nanotube-composited PNIPAM hydrogel. Thus, the PNIPAM stripe is capable of reaching 28 °C at a low environmental temperature (12 °C) and a low radiation intensity (20 mW cm-2), while preventing the body temperature from rising by changing to white under a strong radiation intensity (100 mW cm-2). For the PAM stripe, the upper layer combines colloidal photonic crystals and displays a tunable structural color by stretching, and the lower layer is mixed with PNIPAM microgels for thermal regulation. Through the fabrication of multifunctional patterns, the film can achieve both dynamic structural color and thermoregulation by precisely controlling solar radiation absorption, scattering, and reflection. More importantly, in the stripe-patterned system, the shrinkage of the PNIPAM stripes can effectively trigger the elongation of the PAM stripe, which endows the structural color changing process to be self-powered completely. The performances show that the stripe-patterned film may have potential applications in intelligent coatings, especially in areas with large temperature differences during the day such as high plains.

Thermo-Responsive Hydrogels Encapsulating Targeted Core-Shell Nanoparticles as Injectable Drug Delivery Systems.

As therapeutic agents that allow for minimally invasive administration, injectable biomaterials stand out as effective tools with tunable properties. Furthermore, hydrogels with responsive features present potential platforms for delivering therapeutics to desired sites in the body. Herein, temperature-responsive hydrogel scaffolds with embedded targeted nanoparticles were utilized to achieve controlled drug delivery via local drug administration. Poly(N-isopropylacrylamide) (pNIPAM) hydrogels, prepared with an ethylene-glycol-based cross-linker, demonstrated thermo-sensitive gelation ability upon injection into environments at body temperature. This hydrogel network was engineered to provide a slow and controlled drug release profile by being incorporated with curcumin-loaded nanoparticles bearing high encapsulation efficiency. A core (alginate)-shell (chitosan) nanoparticle design was preferred to ensure the stability of the drug molecules encapsulated in the core and to provide slower drug release. Nanoparticle-embedded hydrogels were shown to release curcumin at least four times slower compared to the free nanoparticle itself and to possess high water uptake capacity and more mechanically stable viscoelastic behavior. Moreover, this therapy has the potential to specifically address tumor tissues over-expressing folate receptors like ovaries, as the nanoparticles target the receptors by folic acid conjugation to the periphery. Together with its temperature-driven injectability, it can be concluded that this hydrogel scaffold with drug-loaded and embedded folate-targeting nanoparticles would provide effective therapy for tumor tissues accessible via minimally invasive routes and be beneficial for post-operative drug administration after tumor resection.