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Keywords = N-isopropylacrylamide

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30 pages, 1761 KB  
Review
Harnessing Optical Energy for Thermal Applications: Innovations and Integrations in Nanoparticle-Mediated Energy Conversion
by José Rubén Morones-Ramírez
Processes 2026, 14(2), 236; https://doi.org/10.3390/pr14020236 - 9 Jan 2026
Viewed by 232
Abstract
Nanoparticle-mediated photothermal conversion exploits the unique light-to-heat transduction properties of engineered nanomaterials to address challenges in energy, water, and healthcare. This review first examines fundamental mechanisms—localized surface plasmon resonance (LSPR) in plasmonic metals and broadband interband transitions in semiconductors—demonstrating how tailored nanoparticle compositions [...] Read more.
Nanoparticle-mediated photothermal conversion exploits the unique light-to-heat transduction properties of engineered nanomaterials to address challenges in energy, water, and healthcare. This review first examines fundamental mechanisms—localized surface plasmon resonance (LSPR) in plasmonic metals and broadband interband transitions in semiconductors—demonstrating how tailored nanoparticle compositions can achieve >96% absorption across 250–2500 nm and photothermal efficiencies exceeding 98% under one-sun illumination (1000 W·m−2, AM 1.5G). Next, we highlight advances in solar steam generation and desalination: floating photothermal receivers on carbonized wood or hydrogels reach >95% efficiency in solar-to-vapor conversion and >2 kg·m−2·h−1 evaporation rates; three-dimensional architectures recapture diffuse flux and ambient heat; and full-spectrum nanofluids (LaB6, Au colloids) extend photothermal harvesting into portable, scalable designs. We then survey photothermal-enhanced thermal energy storage: metal-oxide–paraffin composites, core–shell phase-change material (PCM) nanocapsules, and MXene– polyethylene glycol—PEG—aerogels deliver >85% solar charging efficiencies, reduce supercooling, and improve thermal conductivity. In biomedicine, gold nanoshells, nanorods, and transition-metal dichalcogenide (TMDC) nanosheets enable deep-tissue photothermal therapy (PTT) with imaging guidance, achieving >94% tumor ablation in preclinical and pilot clinical studies. Multifunctional constructs combine PTT with chemotherapy, immunotherapy, or gene regulation, yielding synergistic tumor eradication and durable immune responses. Finally, we explore emerging opto-thermal nanobiosystems—light-triggered gene silencing in microalgae and poly(N-isopropylacrylamide) (PNIPAM)–gold nanoparticle (AuNP) membranes for microfluidic photothermal filtration and control—demonstrating how nanoscale heating enables remote, reversible biological and fluidic functions. We conclude by discussing challenges in scalable nanoparticle synthesis, stability, and integration, and outline future directions: multicomponent high-entropy alloys, modular photothermal–PCM devices, and opto-thermal control in synthetic biology. These interdisciplinary innovations promise sustainable solutions for global energy, water, and healthcare demands. Full article
(This article belongs to the Special Issue Transport and Energy Conversion at the Nanoscale and Molecular Scale)
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18 pages, 3178 KB  
Article
Temperature-Sensitive Properties and Drug Release Processes of Chemically Cross-Linked Poly(N-isopropylacrylamide) Hydrogel: A Molecular Dynamics Simulation
by Guanjie Zeng, Hong Lu, Wenying Zhang, Shuai Yuan and Yusheng Dou
Processes 2026, 14(2), 185; https://doi.org/10.3390/pr14020185 - 6 Jan 2026
Viewed by 220
Abstract
This study utilized a dynamic cross-linking algorithm to formulate a chemical cross-linked hydrogel model of poly(N-isopropylacrylamide) (PNIPAM) with N, N’-methylenebisacrylamide (BIS). Molecular dynamics (MD) simulations were conducted to investigate the temperature sensitivity and ibuprofen release mechanism of this hydrogel under varying cross-linking degrees [...] Read more.
This study utilized a dynamic cross-linking algorithm to formulate a chemical cross-linked hydrogel model of poly(N-isopropylacrylamide) (PNIPAM) with N, N’-methylenebisacrylamide (BIS). Molecular dynamics (MD) simulations were conducted to investigate the temperature sensitivity and ibuprofen release mechanism of this hydrogel under varying cross-linking degrees and water contents. The low critical solution temperature (LCST) of the hydrogel was determined based on changes in solvent-accessible surface area (SASA) and hydrogen bond count. The LCST was found to be between 300 and 310 K. As the temperature increased, both SASA and hydrogen bond counts generally exhibited a gradual decrease. However, near the LCST, polymer chain collapse temporarily exposed the hydrophilic groups of the PNIPAM, forming hydrophilic regions that increased the contact area with water. This led to a transient increase in SASA (8% higher than that before 300 K) and hydrogen bond counts (6.25% higher than that at 290 K). Concurrently, Young’s modulus of the PNIPAM hydrogel was found to decrease with increasing water content (from 3.11 GPa to 2.59 GPa, representing a 16.7% decrease when water content increased from 0% to 50% for 80% cross-linking degree) and increase with rising cross-linking density (from 2.02 GPa to 2.94 GPa, representing a 45.5% increase when the cross-linking degree increased from 0% to 80% for 20% water content). These findings indicate that enhancing cross-linking density is an effective strategy for improving the hydrogel’s mechanical properties. A PNIPAM–ibuprofen delivery model was constructed and molecular dynamics (MD) simulations were conducted, revealing temperature dependence release behavior. Below the LCST, the PNIPAM hydrogel remains in a highly swollen state (PNIPAM single-chain radius of gyration, Rg = 0.64 nm at 290 K), with ibuprofen molecules adsorbed within the PNIPAM polymer chain network. Conversely, above the LCST, PNIPAM undergoes phase separation (Rg decreases to 0.56 nm at 320 K, representing a 12.5% decrease), resulting in volume contraction (cavity volume reduced by 35%) and disruption of the hydrogen bond network. This process results in the release of ibuprofen molecules, accompanied by an increase in their diffusion coefficient from 1.3817 × 10−9 (280 K) to 4.2847 × 10−9 m2/s (320 K). Concurrently, the interaction energy with PNIPAM experiences a decline, from −126.72 kcal/mol to −108.69 kcal/mol. The findings of this study provide insights into the optimization of the structural stability of ibuprofen delivery carriers. Full article
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30 pages, 5119 KB  
Review
Thermo-Responsive Smart Hydrogels: Molecular Engineering, Dynamic Cross-Linking Strategies, and Therapeutics Applications
by Jiten Yadav, Surjeet Chahal, Prashant Kumar and Chandra Kumar
Gels 2026, 12(1), 12; https://doi.org/10.3390/gels12010012 - 23 Dec 2025
Viewed by 550
Abstract
Temperature-responsive hydrogels are sophisticated stimuli-responsive biomaterials that undergo rapid, reversible sol–gel phase transitions in response to subtle thermal stimuli, most notably around physiological temperature. This inherent thermosensitivity enables non-invasive, precise spatiotemporal control of material properties and bioactive payload release, rendering them highly promising [...] Read more.
Temperature-responsive hydrogels are sophisticated stimuli-responsive biomaterials that undergo rapid, reversible sol–gel phase transitions in response to subtle thermal stimuli, most notably around physiological temperature. This inherent thermosensitivity enables non-invasive, precise spatiotemporal control of material properties and bioactive payload release, rendering them highly promising for advanced biomedical applications. This review critically surveys recent advances in the design, synthesis, and translational potential of thermo-responsive hydrogels, emphasizing nanoscale and hybrid architectures optimized for superior tunability and biological performance. Foundational systems remain dominated by poly(N-isopropylacrylamide) (PNIPAAm), which exhibits a sharp lower critical solution temperature near 32 °C, alongside Pluronic/Poloxamer triblock copolymers and thermosensitive cellulose derivatives. Contemporary developments increasingly exploit biohybrid and nanocomposite strategies that incorporate natural polymers such as chitosan, gelatin, or hyaluronic acid with synthetic thermo-responsive segments, yielding materials with markedly enhanced mechanical robustness, biocompatibility, and physiologically relevant transition behavior. Cross-linking methodologies—encompassing covalent chemical approaches, dynamic physical interactions, and radiation-induced polymerization are rigorously assessed for their effects on network topology, swelling/deswelling kinetics, pore structure, and degradation characteristics. Prominent applications include on-demand drug and gene delivery, injectable in situ gelling systems, three-dimensional matrices for cell encapsulation and organoid culture, tissue engineering scaffolds, self-healing wound dressings, and responsive biosensing platforms. The integration of multi-stimuli orthogonality, nanotechnology, and artificial intelligence-guided materials discovery is anticipated to deliver fully programmable, patient-specific hydrogels, establishing them as pivotal enabling technologies in precision and regenerative medicine. Full article
(This article belongs to the Special Issue Characterization Techniques for Hydrogels and Their Applications)
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15 pages, 1819 KB  
Article
Development of a High-Sensitivity Humidity Sensor Using Fiber Bragg Grating Coated with LiCl@UIO-66-Doped Hydrogel
by Binxiaojun Liu, Zelin Gao, Runqi Yao, Liyun Ding and Xusheng Xia
Materials 2025, 18(24), 5587; https://doi.org/10.3390/ma18245587 - 12 Dec 2025
Viewed by 411
Abstract
Humidity monitoring is essential in industrial and scientific scenarios, yet remains challenging for compact EMI (electromagnetic interference)-immune sensors with high sensitivity and robust stability. A novel fiber Bragg grating (FBG) humidity sensor was developed, which incorporated LiCl@UIO-66 microfillers within a poly(N-isopropylacrylamide) (PNIPAM) hydrogel [...] Read more.
Humidity monitoring is essential in industrial and scientific scenarios, yet remains challenging for compact EMI (electromagnetic interference)-immune sensors with high sensitivity and robust stability. A novel fiber Bragg grating (FBG) humidity sensor was developed, which incorporated LiCl@UIO-66 microfillers within a poly(N-isopropylacrylamide) (PNIPAM) hydrogel matrix. Structural characterization using X-ray diffraction (XRD), scanning electron microscopy (SEM), energy-dispersive X-ray spectroscopy (EDS), and Fourier-transform infrared (FTIR) spectroscopy confirms that LiCl is confined or nanodispersed within intact UIO-66, and that interfacial ion–dipole/hydrogen-bonding exists between the composite and water. Systematic variation in coating time (30–720 min) reveals monotonic growth of the total wavelength shift with diminishing returns. A coating time of 4 h was found to yield a wavelength shift of approximately 0.38–0.40 nm, representing about 82% of the maximum shift observed at 12 h, while maintaining good quasi-linearity and favorable kinetics. Calibration demonstrates sensitivities of 6.7 pm/%RH for LiCl@UIO-66_33 and 10.6 pm/%RH for LiCl@UIO-66_51 over ~0–95%RH. Stepwise tests show response times t90 of ≈14 min for both composites, versus ≈30 min for UIO-66 and ≈55 min for neat PNIPAM. Long-term measurements on the 51 wt.% device are stable over the first ~20 days, with only slow drift thereafter, and repeated humidity cycling is reversible. The wavelength decreases monotonically during drying while settling time increases toward low RH. The synergy of hydrogel–MOF–salt underpins high sensitivity, accelerated transport, and practical stability, offering a scalable route to high-performance optical humidity sensing. Full article
(This article belongs to the Special Issue Reinforced Polymer Composites with Natural and Nano Fillers)
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13 pages, 3057 KB  
Article
Injectable Hydrogels with Tissue-Adaptive Gelation and Mechanical Properties: Enhancing Softness and Stability
by Jessica Garcia, Foad Vashahi, Akmal Z. Umarov, Evgeniy V. Dubrovin, Apollinariya Yu. Konyakhina, Elena N. Subcheva, Dimitri A. Ivanov, Andrey V. Dobrynin and Sergei S. Sheiko
Gels 2025, 11(12), 996; https://doi.org/10.3390/gels11120996 - 11 Dec 2025
Viewed by 375
Abstract
Ultra-soft injectable hydrogels are paramount in biomedical applications such as tissue fillers, drug depots, and tissue regeneration scaffolds. Synthetic approaches relying on linear polymers are confronted by the necessity for significant dilution of polymer solutions to reduce chain entanglements. Bottlebrush polymers offer an [...] Read more.
Ultra-soft injectable hydrogels are paramount in biomedical applications such as tissue fillers, drug depots, and tissue regeneration scaffolds. Synthetic approaches relying on linear polymers are confronted by the necessity for significant dilution of polymer solutions to reduce chain entanglements. Bottlebrush polymers offer an alternative approach due to suppressed chain overlap and entanglements, which facilitates lower solution viscosities and increased gel softness. Leveraging the bottlebrush architecture in linear-bottlebrush-linear (LBL) block copolymer systems, where L is a thermosensitive linear poly(N-isopropylacrylamide) block, and B is a hydrophilic polyethylene glycol brush block, injectable hydrogels were designed to mimic tissues as soft as the extracellular matrix at high polymer concentrations. Compared to an analogous system with shorter brush side chains, increasing the side chain length enables a decrease in modulus by up to two orders of magnitude within 1–100 Pa at 20 wt% polymer concentrations, near to the physiological water content of ~70%. This system further exhibits thermal hysteresis, enabling stability with inherent body temperature fluctuations. The observed features are ascribed to kinetically hindered network formation by bulky macromolecules. Full article
(This article belongs to the Section Gel Chemistry and Physics)
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18 pages, 3119 KB  
Article
Physics-Informed Neural Networks for Thermo-Responsive Hydrogel Swelling: Integrating Constitutive Models with Sparse Experimental Data
by Seyed Amirmasoud Takmili, Eunsoo Choi, Alireza Ostadrahimi and Mostafa Baghani
Materials 2025, 18(23), 5401; https://doi.org/10.3390/ma18235401 - 30 Nov 2025
Viewed by 611
Abstract
Poly(N-isopropylacrylamide) (PNIPAM) hydrogels are temperature-sensitive materials whose swelling is difficult to predict near the gel collapse temperature (GCT). A physics-informed neural network (PINN) was developed in which a stabilized free-energy model is embedded and sparse data for free and uniaxially constrained swelling are [...] Read more.
Poly(N-isopropylacrylamide) (PNIPAM) hydrogels are temperature-sensitive materials whose swelling is difficult to predict near the gel collapse temperature (GCT). A physics-informed neural network (PINN) was developed in which a stabilized free-energy model is embedded and sparse data for free and uniaxially constrained swelling are assimilated. Across datasets, the PINN reduces test RMSE by 44% at low crosslink density (Nν = 0.0035) and by 65% at higher density (Nν = 0.02), with coverage inside ±RMSE bands improving from 61.9% to 76.2% for free swelling at Nν = 0.0035. Under constraint, test relative error decreases from 19.95% to 11.86% (n = 1) and from 9.19% to 5.90% (n = 3), while preserving thermodynamic stability. The method sharpens the transition slope near the gel-collapse temperature and narrows prediction intervals without overfitting, capturing cold-regime plateaus and hot-side tails more faithfully. The framework integrates governing equations with data to deliver accurate swelling and stress predictions using only eight anchors and thirteen held-out points per case. These results position PINNs as a reliable surrogate for designing thermo-responsive hydrogels in soft actuators and biomedical systems. Full article
(This article belongs to the Special Issue Modelling of Deformation Characteristics of Materials or Structures)
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16 pages, 7506 KB  
Article
Non-Enzymatic Cell Expansion and Harvesting Using a Smart Thermo-Responsive Gel
by Zhiyu Yan, Nuno Honrado, Naiwen Tan, Md Anirban Jyoti and Linh Nguyen
Gels 2025, 11(12), 962; https://doi.org/10.3390/gels11120962 - 28 Nov 2025
Viewed by 328
Abstract
Advanced cell-based therapies, including immunotherapy, regenerative medicine, and other biotechnological applications, require large quantities of viable mammalian cells for research and clinical use. Conventional enzymatic harvesting methods, such as trypsini-zation, can compromise cell integrity and reduce viability. This study investigates an al-ternative temperature-responsive [...] Read more.
Advanced cell-based therapies, including immunotherapy, regenerative medicine, and other biotechnological applications, require large quantities of viable mammalian cells for research and clinical use. Conventional enzymatic harvesting methods, such as trypsini-zation, can compromise cell integrity and reduce viability. This study investigates an al-ternative temperature-responsive approach using alginate beads incorporated with poly(N-isopropylacrylamide) (PNIPAAm), a polymer exhibiting a lower critical solution temperature (LCST) of approximately 32 °C. This system enables temperature-controlled cell detachment while preserving cellular structure and extracellular matrix components, thereby potentially improving post-harvest viability compared to trypsin treatment. Ho-mogeneous alginate hydrogel beads were synthesized using a standard infusion pump and ionically crosslinked with calcium cations. The beads were characterized by scanning electron microscopy (SEM) for morphology and by Fourier-transform infrared spectroscopy (FTIR), differential scanning calorimetry (DSC), and micro-computed tomography (µ-CT) for compositional and thermal analysis. Mouse fibroblast cells (L929 cell line) were cultured on the beads, and their proliferation and viability were assessed using CCK-8 and Live/Dead assays, demonstrating significant cell growth over seven days. The results suggest that PNIPAAm-modified alginate beads provide a promising, enzyme-free platform for efficient mammalian cell harvesting and delivery, with potential applications across advanced cell manufacturing and therapeutic technologies. Full article
(This article belongs to the Special Issue Biobased Gels for Drugs and Cells)
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14 pages, 7047 KB  
Article
The Potential of Dosimetry and the Visualization of Microbeam Arrays in NIPAM Gel at the PETRA III Synchrotron
by Thomas Breslin, Malin Kügele, Vincent de Rover, Stefan Fiedler, Tobias Lindner, Johannes Klingenberg, Guilherme Abreu Faria, Bernd Frerker, Frank Nuesken, Sofie Ceberg, Crister Ceberg, Michael Lerch, Guido Hildebrandt and Elisabeth Schültke
Gels 2025, 11(10), 814; https://doi.org/10.3390/gels11100814 - 10 Oct 2025
Viewed by 594
Abstract
Spatially fractionated radiotherapy (SFRT) is emerging as a powerful tool in cancer therapy for patients who are ineligible for treatment with clinically established irradiation techniques. Microbeam radiotherapy (MRT) is characterized by spatial dose fractionation in the micrometre range. This presents challenges in both [...] Read more.
Spatially fractionated radiotherapy (SFRT) is emerging as a powerful tool in cancer therapy for patients who are ineligible for treatment with clinically established irradiation techniques. Microbeam radiotherapy (MRT) is characterized by spatial dose fractionation in the micrometre range. This presents challenges in both treatment planning and dosimetry. While a dosimetry system with a spatial resolution of 10 µm and an option for real-time readout already exists, this system can only record dose in a very small volume. Thus, we are exploring dosimetry in an N-isopropylacrylamide (NIPAM) gel as an option for 3D dose visualization and, potentially, also three-dimensional dosimetry in larger volumes. In the current study, we have recorded the geometric patterns of single- and multiport irradiation with microbeam arrays in NIPAM gel. Data for 3D dose distribution was acquired in a 7T small animal MRI scanner. We found that the resolution of the gel is well suited for a detailed 3D visualization of microbeam patterns even in complex multiport geometries, similar to that of radiochromic film, which is well established for recording 2D dose distribution in MRT. The results suggest that a dose–response calibration is required for reliable quantitative dosimetry. Full article
(This article belongs to the Special Issue Application of Gel Dosimetry)
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14 pages, 3103 KB  
Article
Engineering Thermo-Responsive Hydrogels with Tailored Mechanics for Biomedical Integration
by Sungmo Choi, Minkyeong Pyo, Sangmin Lee, Yunseo Jeong, Yuri Nam, Seonghyeon Park, Yoon-A Jang, Kisung Kim and Chan Ho Park
Polymers 2025, 17(17), 2424; https://doi.org/10.3390/polym17172424 - 8 Sep 2025
Cited by 1 | Viewed by 1328
Abstract
Poly(N-isopropylacrylamide) (PNIPAAm) hydrogels exhibit temperature-responsive volume changes near physiological temperature, but their low mechanical strength in the swollen state limits use in structurally demanding biomedical applications. In this study, we systematically investigated poly(NIPAAm-co-acrylamide), P(NIPAAm-co-AAm), hydrogels with varying AAm-to-NIPAAm ratios to explore the compositional [...] Read more.
Poly(N-isopropylacrylamide) (PNIPAAm) hydrogels exhibit temperature-responsive volume changes near physiological temperature, but their low mechanical strength in the swollen state limits use in structurally demanding biomedical applications. In this study, we systematically investigated poly(NIPAAm-co-acrylamide), P(NIPAAm-co-AAm), hydrogels with varying AAm-to-NIPAAm ratios to explore the compositional trade-offs between thermal responsiveness and mechanical performance. Hydrogels were synthesized under fixed crosslinker and water content conditions, and evaluated through compressive mechanical testing, thermal swelling analysis, and crosslinking density estimation. Our results show that increasing AAm content enhances mechanical strength and stiffness but reduces the magnitude of temperature-induced volumetric shrinkage. An intermediate comonomer formulation demonstrated an optimal balance, maintaining both sufficient mechanical integrity for transdermal microneedle insertion and a reversible volume transition. This study highlights the potential of compositional tuning in hydrogel systems to meet the competing demands of responsiveness and durability in advanced biomedical applications. Full article
(This article belongs to the Special Issue Smart Polymeric Materials for Biomedical Applications)
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15 pages, 9602 KB  
Article
Photothermal and Magnetic Actuation of Multimodal PNIPAM Hydrogel-Based Soft Robots
by Xiangyu Teng, Zhizheng Gao, Xuehao Feng, Shuliang Zhu and Wenguang Yang
Gels 2025, 11(9), 692; https://doi.org/10.3390/gels11090692 - 1 Sep 2025
Viewed by 1250
Abstract
Soft robot motion performance has long been a core focus in scientific research. This study investigates the motion capabilities of soft robots constructed using poly(N-isopropylacrylamide) (PNIPAM) hydrogels, with key innovations in material design and functional enhancement. By optimizing the hydrogel formulation and incorporating [...] Read more.
Soft robot motion performance has long been a core focus in scientific research. This study investigates the motion capabilities of soft robots constructed using poly(N-isopropylacrylamide) (PNIPAM) hydrogels, with key innovations in material design and functional enhancement. By optimizing the hydrogel formulation and incorporating molybdenum disulfide (MoS2) to endow it with photothermal response properties, the material achieves muscle-like controllable contraction and expansion deformation—a critical breakthrough in mimicking biological motion mechanics. Building on this material advancement, the research team developed a series of soft robotic prototypes to systematically explore the hydrogel’s motion characteristics. A flytrap-inspired soft robot demonstrates rapid opening–closing movements, replicating the swift responsiveness of natural carnivorous plants. For terrestrial locomotion, a hexapod crawling robot utilizes the photo-induced stretch-recovery mechanism of both horizontally configured and pre-bent feet to achieve stable directional propulsion. Most notably, a magnetically driven rolling robot integrates magnetic units to realize versatile multimodal movement: it achieves a stable rolling speed of 1.8 cm/s across flat surfaces and can surmount obstacles up to 1.5 times its own body size. This work not only validates the strong potential of PNIPAM hydrogel-based soft robots in executing complex motion tasks but also provides valuable new insights for the development of multimodal soft robotic systems, paving the way for future innovations in adaptive and bio-inspired robotics. Full article
(This article belongs to the Special Issue Functional Hydrogels for Soft Electronics and Robotic Applications)
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12 pages, 1561 KB  
Article
Effect of Performance and Fouling Mechanisms of Thermo-Responsive Membranes on Treating Secondary Effluent Containing Added Sulfamethoxazole
by Lian Yang, Haoran Qiu, Yingjie Yang, Lijun Zhao, Ping Xiao, Guoliang Liu, Jiang Chang, Shaoxia Yang and Feng Xiao
Separations 2025, 12(8), 218; https://doi.org/10.3390/separations12080218 - 16 Aug 2025
Viewed by 649
Abstract
Wastewater treatment plants generally lack a specialized design for the efficient removal of sulfamethoxazole (SMX), a toxic and bio-resistant compound. In this study, secondary effluent from a Beijing wastewater reclamation treatment plant was spiked with SMX and used to investigate the filtration performance [...] Read more.
Wastewater treatment plants generally lack a specialized design for the efficient removal of sulfamethoxazole (SMX), a toxic and bio-resistant compound. In this study, secondary effluent from a Beijing wastewater reclamation treatment plant was spiked with SMX and used to investigate the filtration performance and fouling mechanisms of thermo-responsive membranes. Thermo-responsive materials were prepared using polyvinylidene fluoride, N-isopropylacrylamide (NIPAM), and graphene oxide through Ce (IV)-induced redox radical polymerization. The results showed that the removal of SMX and COD reached 42% and 92%, respectively, with a NIPAM dosage of 1 g, and the removal of UV254 reached its highest value at 57.9%. Additionally, the filtration flux was higher at a temperature of 35 °C with a NIPAM dosage of 1 g. The fluorescence intensity of the organic matter from the secondary effluent spiked with SMX and decreased after the thermo-responsive membranes were implemented, and filtration with the membrane containing 1 g of NIPAM achieved a lower intensity at a value of 3074.6, according to the analysis of three-dimensional fluorescence excitation–emission spectroscopy. According to the extended Derjaguin–Laudau–Verwey–Overbeek theory analysis, the interfacial free energies of the thermo-responsive membrane with a 1 g dose of NIPAM were higher than the others during filtration. Full article
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27 pages, 3312 KB  
Review
Influence of Structure–Property Relationships of Polymeric Biomaterials for Engineering Multicellular Spheroids
by Sheetal Chowdhury and Amol V. Janorkar
Bioengineering 2025, 12(8), 857; https://doi.org/10.3390/bioengineering12080857 - 9 Aug 2025
Cited by 3 | Viewed by 1623
Abstract
Two-dimensional cell culture systems lack the ability to replicate the complex, three-dimensional (3D) architecture and cellular microenvironments found in vivo. Multicellular spheroids (MCSs) present a promising alternative, with the ability to mimic native cell–cell and cell–matrix interactions and provide 3D architectures similar to [...] Read more.
Two-dimensional cell culture systems lack the ability to replicate the complex, three-dimensional (3D) architecture and cellular microenvironments found in vivo. Multicellular spheroids (MCSs) present a promising alternative, with the ability to mimic native cell–cell and cell–matrix interactions and provide 3D architectures similar to in vivo conditions. These factors are critical for various biomedical applications, including cancer research, tissue engineering, and drug discovery and development. Polymeric materials such as hydrogels, solid scaffolds, and ultra-low attachment surfaces serve as versatile platforms for 3D cell culture, offering tailored biochemical and mechanical cues to support cellular organization. This review article focuses on the structure–property relationships of polymeric biomaterials that influence MCS formation, growth, and functionality. Specifically, we highlight their physicochemical properties and their influence on spheroid formation using key natural polymers, including collagen, hyaluronic acid, chitosan, and synthetic polymers like poly(lactic-co-glycolic acid) and poly(N-isopropylacrylamide) as examples. Despite recent advances, several challenges persist, including spheroid loss during media changes, limited viability or function in long-term cultures, and difficulties in scaling for high-throughput applications. Importantly, the development of MCS platforms also supports the 3R principle (Replacement, Reduction, and Refinement) by offering ethical and physiologically relevant alternatives to animal testing. This review emphasizes the need for innovative biomaterials and methodologies to overcome these limitations, ultimately advancing the utility of MCSs in biomedical research. Full article
(This article belongs to the Special Issue 3D Cell Culture Systems: Current Technologies and Applications)
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24 pages, 6999 KB  
Article
Plasmid DNA Delivery to Cancer Cells with Poly(L-lysine)-Based Copolymers Bearing Thermally Sensitive Segments: Balancing Polyplex Tightness, Transfection Efficiency, and Biocompatibility
by Mustafa Kotmakci, Natalia Toncheva-Moncheva, Sahar Tarkavannezhad, Bilge Debelec Butuner, Ivaylo Dimitrov and Stanislav Rangelov
Pharmaceutics 2025, 17(8), 1012; https://doi.org/10.3390/pharmaceutics17081012 - 2 Aug 2025
Viewed by 1579
Abstract
Background/Objectives. Efficient nucleic acid delivery into target cells remains a critical challenge in gene therapy. Due to its advantages in biocompatibility and safety, recent research has increasingly focused on non-viral gene delivery. Methods. A series of copolymers—synthesized by integrating thermally sensitive poly(N-isopropylacrylamide) [...] Read more.
Background/Objectives. Efficient nucleic acid delivery into target cells remains a critical challenge in gene therapy. Due to its advantages in biocompatibility and safety, recent research has increasingly focused on non-viral gene delivery. Methods. A series of copolymers—synthesized by integrating thermally sensitive poly(N-isopropylacrylamide) (PNIPAm), hydrophilic poly(ethylene glycol) (PEG) grafts, and a polycationic poly(L-lysine) (PLL) block of varying lengths ((PNIPAm)77-graft-(PEG)9-block-(PLL)z, z = 10–65)—were investigated. Plasmid DNA complexation with the copolymers was achieved through temperature-modulated methods. The resulting polyplexes were characterized by evaluating complex strength, particle size, zeta potential, plasmid DNA loading capacity, resistance to anionic stress, stability in serum, and lysosomal membrane destabilization assay. The copolymers’ potential for plasmid DNA delivery was assessed through cytotoxicity and transfection studies in cancer cell lines. Results. Across all complexation methods, the copolymers effectively condensed plasmid DNA into stable polyplexes. Particle sizes (60–90 nm) ranged with no apparent correlation to copolymer type, complexation method, or N/P ratio, whereas zeta potentials (+10–+20 mV) and resistance to polyanionic stress were dependent on the PLL length and N/P ratio. Cytotoxicity analysis revealed a direct correlation between PLL chain length and cell viability, with all copolymers demonstrating minimal cytotoxicity at concentrations required for efficient transfection. PNL-20 ((PNIPAm)77-graft-(PEG)9-block-(PLL)20) exhibited the highest transfection efficiency among the tested formulations while maintaining low cytotoxicity. Conclusions. The study highlights the promising potential of (PNIPAm)77-graft-(PEG)9-block-(PLL)z copolymers for effective plasmid DNA delivery to cancer cells. It reveals the importance of attaining the right balance between polyplex tightness and plasmid release to achieve improved biocompatibility and transfection efficiency. Full article
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15 pages, 2741 KB  
Article
Development of a Curcumin-Loaded Hyaluronic Acid Nanogel Formulation Using Wet Granulation Method for Enhanced Dissolution and Stability
by Natkhanang Mookkie Boonpetcharat, May Thu Thu Kyaw, Veerakiet Boonkanokwong and Jittima Amie Luckanagul
Gels 2025, 11(8), 585; https://doi.org/10.3390/gels11080585 - 29 Jul 2025
Cited by 1 | Viewed by 2219
Abstract
Curcumin is widely recognized for its various pharmacological properties, including antioxidant, anti-inflammatory, and anti-tumor activities. Nevertheless, the development of curcumin as a therapeutic agent is impeded by its limited oral bioavailability, which stems from its chemical instability, poor aqueous solubility, and rapid degradation. [...] Read more.
Curcumin is widely recognized for its various pharmacological properties, including antioxidant, anti-inflammatory, and anti-tumor activities. Nevertheless, the development of curcumin as a therapeutic agent is impeded by its limited oral bioavailability, which stems from its chemical instability, poor aqueous solubility, and rapid degradation. This study aimed to develop granule formulations incorporating poly(N-isopropylacrylamide)-grafted hyaluronic acid or HA-g-pNIPAM to enhance dissolution and protect curcumin from degradation. Three formulations were developed: F10 (HA-g-pNIPAM physically mixed with curcumin), F10 Encap (curcumin encapsulated within HA-g-pNIPAM), and F11 (curcumin granules without HA-g-pNIPAM). The stability results showed that F10 Encap effectively maintained curcumin content throughout the study period, retaining approximately 94% of its initial concentration by day 30, compared to 70% from F11 (p < 0.05) at 30 °C and 75% relative humidity. All dried curcumin granules exhibited excellent flowability, as determined by the angle of repose measurements. All three formulations exhibited a consistent particle size distribution across replicates, with a peak in the 150–180 μm size range. The sustained release observed for F10 Encap and F10 after the initial burst suggested that the HA-g-pNIPAM provided a controlled release mechanism, ensuring continuous curcumin dissolution over 240 min in gastric and intestinal conditions. These findings suggested that HA-g-pNIPAM improved dissolution and stability of curcumin. Full article
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19 pages, 4349 KB  
Article
Thermoresponsive Behavior, Degradation, and Bioactivity of Nanohydroxyapatite on Graphene Oxide Nanoscroll-Enhanced Poly(N-isopropylacrylamide)-Based Scaffolds
by Lillian Tsitsi Mambiri, Riley Guillory and Dilip Depan
Polymers 2025, 17(15), 2014; https://doi.org/10.3390/polym17152014 - 23 Jul 2025
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Abstract
Osteoarthritis and metastatic bone cancers create pathological oxidative environments characterized by elevated reactive oxygen species (ROS). ROS impair bone regeneration by degrading the scaffold and suppressing mineralization. To address these challenges, we fabricated thermoresponsive scaffolds based on poly(N-isopropylacrylamide) (PNIPAAm) incorporating in situ-grown nanohydroxyapatite [...] Read more.
Osteoarthritis and metastatic bone cancers create pathological oxidative environments characterized by elevated reactive oxygen species (ROS). ROS impair bone regeneration by degrading the scaffold and suppressing mineralization. To address these challenges, we fabricated thermoresponsive scaffolds based on poly(N-isopropylacrylamide) (PNIPAAm) incorporating in situ-grown nanohydroxyapatite on graphene oxide nanoscrolls (nHA-GONS) using stereolithography (SLA). Three scaffold formulations were studied: pure PNIPAAm (PNP), PNIPAAm with 5 wt.% nHA-GONS (P5G), and PNIPAAm with 5 wt.% nHA-GONS reinforced with polycaprolactone (PCL) microspheres (PN5GP). Each scaffold was evaluated for (i) swelling and lower critical solution temperature (LCST) using differential scanning calorimetry (DSC); (ii) oxidative degradation assessed using Fourier-transform infrared spectroscopy (FTIR), mass loss, and antioxidant assays; and (iii) mineralization and morphology via immersion in simulated body fluid followed by microscopy. The PN5GP and P5G scaffolds demonstrated reversible swelling, sustained antioxidant activity, and enhanced calcium deposition, which enable redox stability and mineralization under oxidative environments, critical for scaffold functionality in bone repair. PNP scaffolds exhibited copper accumulation, while PN5GP suffered from accelerated mass loss driven by the PCL phase. These findings identify the P5G formulation as a promising scaffold. This study introduces a quantitative framework that enables the predictive design of oxidation-resilient scaffolds. Full article
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