Cross-linked Hydrophilic Polymers Research Articles

Cross-linked hydrophilic polymers: universal sensors for analyzing solutions containing polar organic compounds

Abstract This study presents a quantitative assessment of cross-linked polyvinyl alcohol (PVA) granules as sensing elements for detecting aliphatic carboxylic acids and their sodium salts in aqueous solutions. Swelling kinetics were measured across solute concentrations ranging from 0.2 N to 1.0 N, with the granule radius varying between 0.31- and 0.43-mm. Results indicated that both carbon chain length and the presence of additional carboxyl groups exert a pronounced effect on the equilibrium swelling degree, thereby highlighting the interplay between hydrophobic interactions and hydrogen-bond formation. To interpret these observations, a heterophase physicomathematical model was employed, yielding three main kinetic coefficients (K1, K2, and K3) that capture solvent flux, polymer network elasticity, and solute transport. The model fits exhibited root-mean-square deviations below 1 %, attesting to its reliability in describing complex swelling - deswelling processes. Additionally, three-dimensional kinetic surfaces were constructed to illustrate how swelling evolves over time and concentration, revealing that initial swelling curves can serve as a rapid indicator of solute concentration. By leveraging the reversible nature of polymer swelling, this method offers a non-invasive, cost-effective approach suitable for monitoring organic acids in diverse fields such as environmental analysis, pharmaceutical processes, and chemical engineering.

The versatility of peptide hydrogels: From self-assembly to drug delivery applications.

Pharmaceuticals often suffer from limitations such as low solubility, low stability, and short half-life. To address these challenges and reduce the need for frequent drug administrations, a more efficient delivery is required. In this context, the development of controlled drug delivery systems, acting as a protective depot for the drug, has expanded significantly over the last decades. Among these, injectable hydrogels have emerged as a promising platform, especially in view of the rise of biologicals as therapeutics. Hydrogels are functional, solid-like biomaterials, composed of cross-linked hydrophilic polymers and high water content. Their physical properties, which closely mimic the extracellular matrix, make them suitable for various biomedical applications. This review discusses the different types of hydrogel systems and their self-assembly process, with an emphasis on peptide-based hydrogels. Due to their structural and functional diversity, biocompatibility, synthetic accessibility, and tunability, peptides are regarded as promising and versatile building blocks. A comprehensive overview of the variety of peptide hydrogels is outlined, with β-sheet forming sequences being highlighted. Key factors to consider when using peptide hydrogels as a controlled drug delivery system are reviewed, along with a discussion of the main drug release mechanisms and the emerging trend towards affinity-based systems to further refine drug release profiles.

Increasing the Economic Value of Hydrogel as an Alternative Planting Media at Madrasah Aliyah Swasta Muhammadiyah Sidomulyo

Hydrogel technology can be used as a solution for indoor growing media. Hydrogel is a three-dimensional polymer network with cross-linked hydrophilic polymers, which are capable of swelling or storing water and physiological solutions up to thousands of times their dry weight, and are not easily soluble. To increase knowledge about ornamental plant cultivation using hydrogel media, a service was carried out by using partners at the Madrasah Aliyah Swasta Muhammadiyah Sidomulyo. This service aims to provide solutions to partners in the form of alternative hydrogel-based planting media made from alginate that are environmentally friendly which can be used as moisture and nutrient control agents. This goal is achieved through outreach activities, training, and the application of alternative planting media on ornamental plants. The target of the results to be achieved is to increase the economic value of hydrogels and to foster the entrepreneurial spirit of the students of Madrasah Aliyah Swasta Muhammadiyah Sidomulyo.

A Wearable Thin-Film Hydrogel Laser for Functional Sensing on Skin.

Flexible photonics offers the possibility of realizing wearable sensors by bridging the advantages of flexible materials and photonic sensing elements. Recently, optical resonators have emerged as a tool to improve their oversensitivity by integrating with flexible photonic sensors. However, direct monitoring of multiple psychological information on human skin remains challenging due to the subtle biological signals and complex tissue interface. To tackle the current challenges, here, we developed a functional thin film laser formed by encapsulating liquid crystal droplet lasers in a flexible hydrogel for monitoring metabolites in human sweat (lactate, glucose, and urea). The three-dimensional cross-linked hydrophilic polymer serves as the adhesive layer to allow small molecules to penetrate from human tissue to generate strong light--matter interactions on the interface of whispering gallery modes resonators. Both the hydrogel and cholesteric liquid crystal microdroplets were modified specifically to achieve high sensitivity and selectivity. As a proof of concept, wavelength-multiplexed sensing and a prototype were demonstrated on human skin to detect human metabolites from perspiration. These results present a significant advance in the fabrication and potential guidance for wearable and functional microlasers in healthcare.

Advances in hydrogel materials applied to pancreatic-related diseases

The pancreas is a glandular organ that maintains internal homeostasis through its endocrine and exocrine functions. These functions are vital for overall well-being. However, environmental and lifestyle changes have led to an increasing incidence of pancreatic diseases, including pancreatic cancer, pancreatitis, and pancreatic neuroendocrine tumors. These conditions profoundly impact the health and quality of life of affected individuals. The existing diagnostic and treatment approaches for pancreatic diseases exhibit limitations and shortcomings, necessitating exploring novel strategies. In recent years, advancements in medicine and bioengineering have fostered multidisciplinary and interdisciplinary innovations, introducing fresh avenues for diagnosing and treating pancreatic diseases. Hydrogels, emerging as a biomaterial, represent highly hydrated cross-linked hydrophilic polymer networks. Their exceptional biodegradability and biocompatibility have rendered them instrumental in various medical applications. Hydrogels, with their macromolecular porous structures, are efficient carriers for drug delivery and controlled release. Hydrogel materials have garnered substantial attention for their unique properties and diverse applications in the context of pancreatic diseases. This article aims to provide an overview of the current limitations in diagnosing and treating pancreatic diseases while highlighting the latest trends and advancements in developing hydrogel carrier materials tailored for these conditions, primarily focusing on strategies for pancreatitis, pancreatic cancer, and pancreatic neuroendocrine tumors. The article endeavors to give researchers and clinicians a comprehensive grasp of this field, offering valuable insights into prospective research directions and emerging trends.

Significant Interfacial Dielectric Relaxation of Covalently Bonded Ice-Hydrogels.

Hydrogels are composed of a three-dimensional network of cross-linked hydrophilic polymer chains and large amounts of water. The physicochemical properties of the polymer-water interface in hydrogels draw our attention. Due to the complex structure of hydrogel systems, it is still a challenge to investigate the interfacial layer properties of hydrogels through experiments. In this work, we investigate the properties of the covalently bonded chitosan-based ice-hydrogels interfacial layer by dielectric relaxation spectroscopy (DRS) techniques in the presence of avoided electrode polarization. The DRS data exhibit that the polymer-water interfacial layer has a strong dielectric signal response, which indicates that a large number of polar electric dipoles or polar molecules may be contained in the interfacial layer. The variable temperature dielectric relaxation behavior of a series of chitosan-base ice-hydrogels showed that the value of dielectric activation energy for different water contents is about 180 kJ/mol, which is much larger than that of the polymer and ice phases, suggesting a strong coupling of polar electric dipoles within the interfacial layer. This work demonstrates the important role of the polymer-water interface in covalently bonded hydrogels, which will provide assistance in the design and application of covalently bonded hydrogels.

Superabsorbent polymer as a supplement substrate of constructed wetland to retain pesticides from agricultural runoff

Surface water runoff can export pesticides from agricultural fields into adjacent aquatic ecosystems, where they may pose adverse effects to organisms. Constructed wetlands (CWs) are widely used to treat agricultural runoff contaminated by pesticides, but the removal of hydrophilic pesticides is usually low. In this study, we suggest superabsorbent polymer (SAP), a cross-linked hydrophilic polymer, as a supplement to substrates of CWs and tested the hypothesis that SAP results in an enhanced removal of hydrophilic pesticides. Therefore, batch experiments were conducted to study the retention capacity of water-saturated SAP (w-SAP) for several hydrophilic pesticides. Retention of the pesticides on w-SAP was related to the ionization state and water solubility of the pesticides. The retention of neutral pesticides, imidacloprid, metalaxyl and propiconazole, was about 20% higher than that measured for anionic pesticides, bentazone, glyphosate and MCPA. The retention of the pesticides by w-SAP mainly resulted from their distribution in the gel-water phase of w-SAP, while less water soluble pesticides might have also been adsorbed on the molecular backbone of SAP. Furthermore, we tested the efficacy of w-SAP for treatment of runoff water contaminated by pesticides in lab-scale horizontal subsurface flow CWs. SAP in CWs improved the removal of the pesticides, including the recalcitrant ones. The removal enhancement was owing to the increase of hydraulic retention time and improvement of biodegradation. The removal of the pesticides in SAP containing CWs was > 93% for MCPA, glyphosate, and propiconazole, 62 – 99% for imidacloprid, 50 – 84% for metalaxyl, and 38 – 73% for bentazone. In the control gravel CWs, the removal was > 98% for glyphosate, generally > 83% for MCPA and propiconazole, 46 – 98% for imidacloprid, 32 – 97% for metalaxyl, and 9 – 96% for bentazone.

Recent Development in the Visualization of Microgels

Hydrogel microspheres (microgels) are water-swollen, soft colloidal particles composed of cross-linked hydrophilic or amphiphilic polymer chains. Due to their fascinating properties such as biocompatibility, colloidal stability, and rapid stimulus responsivity, microgels are expected to find numerous applications in a wide variety of fields. The understanding and development of microgels with colloidal-sized dimensions has been propelled in particular by visualization techniques. Their history and recent progress in microgel evaluation using such visualization techniques are summarized in this review.

In vivo molecular imaging for immunotherapy using ultra-bright near-infrared-IIb rare-earth nanoparticles.

The NIR-IIb (1500–1700 nm) window is ideal for deep-tissue optical imaging in mammals, but lacks bright and biocompatible probes. Here, we developed biocompatible cubic-phase (α-phase) erbium-based rare-earth nanoparticles (ErNPs) exhibiting bright downconversion luminescence at ~ 1600 nm for dynamic imaging of cancer immune-therapy in mice. We used ErNPs functionalized with cross-linked hydrophilic polymer layers attached to anti-PD-L1 antibody for molecular imaging of PD-L1 in a mouse model of colon cancer and achieved tumor to normal tissue signal ratios of ~ 40. The long luminescence lifetime of ErNPs (~ 4.6 ms) enabled simultaneous imaging of ErNPs and lead sulfide quantum dots (PbS QDs) emitting in the same ~ 1600 nm window. In vivo NIR-IIb molecular imaging of PD-L1 and CD8 revealed cytotoxic T lymphocytes in the tumor microenvironment in response to immunotherapy, and altered CD8 signals in tumor and spleen due to immune activation. The novel crosslinked functionalization layer facilitated 90% ErNPs excretion within two weeks without detectable toxicity in mice.

Fast and stable optical pH sensor materials for oceanographic applications

The study reports preparation and detailed comparison of four new pH sensor materials for seawater measurements. The composition of the sensors is optimized in several iterations to ensure optimal dynamic range, fast response time at low temperatures, low cross-sensitivities to temperature (dpKa/dT ∼ -0.013 pH units/K) and negligible cross sensitivity to ionic strength above salinity 15 PSU. The first generation (material “pH-1″) utilizes a pH indicator which is physically entrapped into a polyurethane hydrogel. This material shows satisfactory performance only at comparably high temperatures with response times being extremely long at low temperatures (t95 > 2 h at 5 °C). The three other materials utilize cross-linked hydrophilic polymers based on poly(acryloylmorpholine) with indicator dye covalently coupled to the polymer. They feature fast response times at low temperatures (t90 < 1 min at 5 °C). Moreover, the last two generations (“pH-3″ and “pH-4″) showed no drift over 54 days at 10 °C and only a drift of 0.003 pH units/day at 25 °C. Although the stability and the sensing properties of these materials are rather similar, the synthetic effort varies considerably. The material of the fourth generation “pH-4″ explores a novel approach of covalent coupling via B–O linkage and is characterized by low synthetic effort and the pKa value optimal for seawater measurements (8.05 at 20 °C). Importantly, all new sensor materials are spectrally compatible to a recently presented seawater optode system for combined pH, pO2 and pCO2 measurements which facilitates their application in marine environment.

(Invited) Micro-Manipulation of Hydrogel Sheet through Photoresponsive Polymer Dissolution

Various functional hydrogels have been developed, and their applications to the fields of bioengineering have been examined actively. In these situations, we developed novel technologies to manipulate hydrogel sheet and living cells through photoresponsive polymer dissolution. Firstly, we proposed the fabrication of unique hydrogel microstructures through photolithography. As a photo-acid-generation (PAG) polymer, we synthesized a poly(methylmethacrylate) functionalized with visible- light-responsive PAG group (pPAGMMA), and spin-coated polystyrene surface with the polymer solution. Then we overcoated pregel solution containing hydrophilic polymer (hydroxypropyl cellulose) (HPC) and 1,3,4,6-Tetrakis(methoxymethyl)glycoluril, and carried out micro-patterned light projection. After post-bake and flushing, we obtained crosslinked hydrophilic polymer sheet only in the irradiated area. Due to another property of pPAGMMA getting dissolved in ethanol/water mixture by further irradiation, the cross-linked hydrophilic polymer sheet was lifted from the substrate surface and became swollen in the desired areas by the second micro-patterned projection in ethanol/water mixture. As a result, we obtained various microstructures which were composed of patterned swollen hydrogel sheet partially attached to the substrate in the patterned areas. Secondly, we developed a novel photoresponsive polymer materials by functionalizing poly(N-isopropylacrylamide) with o-nitrobenzaldehyde (pNBANIPAAm) to implement in situ photocontrol in aqueous systems containing bio-compatible environment. We observed that the polymer exhibited sharp aqueous dissolution upon light irradiation in wide pH range including biological conditions. We prepared closs-linked HPC (cHPC) layer on pNBANIPAAm thin layer and carried out micropatterned light projection in PBS. As a result, we observed that the cHPC layer lifted off of the substrate and swelled while nothing happened in unirradiated areas. Also living cells were manipulated by light in a similar manner.

High-Speed AFM Reveals the Detailed Mechanism of Dynamic Protein Adsorption Onto Individual Hydrogel Microspheres

Hydrogel microspheres, i.e., microgels have both colloidal and hydrogel properties, which are composed of cross-linked hydrophilic polymer network. Due to the colloidal size property and biocompatibility, microgels are promising for advanced bio-nanomaterials such as protein drug delivery vehicles [1]. In order to establish the design concept of such protein carrier, understanding the dynamic interaction between the protein and microgels is essential. Up to now, the dynamic interaction between protein and microgels is well characterize by means of scattering, spectroscopy, and sensor [2]. However, to the best of our knowledge, there are no study that direct visualization during protein adsorption to individual microgels at nanoscale in real-time. Against this background, we visualized individual microgels during protein adsorption onto the microgels at nanoscale in real-time for the first time [3]. This approach, which enabled us to monitor the moment of protein adsorption to individual microgels, was realized by high-speed atomic force microscopy (HS-AFM) [4]. This method allows the direct visualization of the dynamics of biological molecules in action, without significantly disturbing the physiological function of the molecules [5]. We have already monitored the dynamic adsorption behavior of microgels onto solid/liquid interface [6]. The microgels were synthesized through aqueous free-radical precipitation polymerization of N-isopropyl acrylamide, the cross-linker N,N'-methylenebis (acrylamide), and acrylic acid with different content. In this presentation, the effect of protein interaction on the microgels’ dynamics will be discussed. Partially reproduced with permission from [6] Copyright (2017) John Wiley and Sons.

Swelling kinetics of cross-linked polymer gels based on polystyrene and poly(vinyl alcohol) in aqueous solutions of electrolytes and sucrose

The swelling kinetics of polymer gels has been studied in water and aqueous solutions by optical micrometry. Cross-linked hydrophilic polymers based on polystyrene and poly(vinyl alcohol) have been used as gel-forming materials. The effects of the natures of the matrices and polar groups of the polymers and their cross-linking densities and granule sizes, as well as the properties of external phase, on the swelling kinetics of the polymer gels have been investigated. The experimental results have been processed in terms of a heterophase kinetic model. The applicability of the model to describing the behavior of all studied systems has been shown.

Preparation of Poly Acrylic Acid-Poly Acrylamide Composite Nanogels by Radiation Technique.

Nanogel, a nanoparticle prepared from a cross-linked hydrophilic polymer network, has many biomedical applications. A radiation technique has recently been introduced as one of the appropriate methods for the preparation of polymeric nanogels due to its additive-free initiation and easy control procedure. We have investigated the formation of nano-sized polymeric gels, based on the radiation-induced inter- and intra-molecular cross-linking of the inter-polymer complex (IPC) of polyacrylamide (PAAm) and polyacrylic acide (PAAc). The results indicated that the prepared polymeric complex composed of PAAm and PAAc was converted into nanogel by irradiation under different doses (1, 3, 5 and 7 kGy). This was due to inter- and intra-molecular cross-linking at the range of 446-930 nm as characterized by the photon correlation spectroscopy method. Increasing the irradiation dose reduced the size of nanoparticles to 3 kGy; however, the higher doses increased the size and size distribution. Scanning electron microscopy images indicated the nanogel formation in the reported size by particle size and showed the microcapsule structure of the prepared nanogels. Biocompatibility of nanogels were assessed and proved by MTT assay. It was concluded that low dose irradiation can be successfully applied for nanometre-ranged hydrogel.

Alginate/polyoxyethylene and alginate/gelatin hydrogels: preparation, characterization, and application in tissue engineering.

Hydrogels are attractive biomaterials for three-dimensional cell culture and tissue engineering applications. The preparation of hydrogels using alginate and gelatin provides cross-linked hydrophilic polymers that can swell but do not dissolve in water. In this work, we first reinforced pure alginate by using polyoxyethylene as a supporting material. In an alginate/PEO sample that contains 20 % polyoxyethylene, we obtained a stable hydrogel for cell culture experiments. We also prepared a stable alginate/gelatin hydrogel by cross-linking a periodate-oxidized alginate with another functional component such as gelatin. The hydrogels were found to have a high fluid uptake. In this work, preparation, characterization, swelling, and surface properties of these scaffold materials were described. Lyophilized scaffolds obtained from hydrogels were used for cell viability experiments, and the results were presented in detail.

Recent Patents on Stimuli Responsive Hydrogel Drug Delivery System

Hydrogels are cross-linked hydrophilic polymer structures that imbibe large quantities of water or biological fluids. Hydrogels are an upcoming class of polymer-based controlled release drug delivery systems, embracing numerous biomedical and pharmaceutical applications. Hydrogels are swellable polymeric materials, and are being widely investigated as a carrier for drug delivery systems. Besides exhibiting swelling-controlled drug release, hydrogels also show stimuli responsive changes in their structural network and hence leading to the drug release. The present manuscript is concerned with the classification, method of preparation; application in drug deliveryand FDA approved market products of hydrogels with the patent review on hydrogel composition and its manufacturing process. It also highlights recent advances in hydrogel drug delivery especially stimuli-responsive hydrogel and its patents. This patent review is useful in the synthesis methods of hydrogel drug delivery and its application.

Responsive DNA-based hydrogels and their applications.

The term hydrogel describes a type of soft and wet material formed by cross-linked hydrophilic polymers. The distinct feature of hydrogels is their ability to absorb a large amount of water and swell. The properties of a hydrogel are usually determined by the chemical properties of their constituent polymer(s). However, a group of hydrogels, called "smart hydrogels," changes properties in response to environmental changes or external stimuli. Recently, DNA or DNA-inspired responsive hydrogels have attracted considerable attention in construction of smart hydrogels because of the intrinsic advantages of DNA. As a biological polymer, DNA is hydrophilic, biocompatible, and highly programmable by Watson-Crick base pairing. DNA can form a hydrogel by itself under certain conditions, and it can also be incorporated into synthetic polymers to form DNA-hybrid hydrogels. Functional DNAs, such as aptamers and DNAzymes, provide additional molecular recognition capabilities and versatility. In this Review, DNA-based hydrogels are discussed in terms of their stimulus response, as well as their applications.

Effects of super-absorbent polymer on dry matter accumulation and nutrient uptake of Pinus pinaster container seedlings

Super-absorbent polymer (SAP) is a widely studied cross-linked hydrophilic polymer used as water absorbent material. However, little information is available concerning the effects of SAPs on the growth and nutrient accumulation in forest container seedlings. The present study was conducted to quantify the effects of SAP applied with or without fertilizer on the dry matter and nutrient uptake of Pinus pinaster container seedlings. SAP addition with fertilizer increased dry matter along with increased seedling emergence time. However, no effect was found without fertilizer. Compared with fertilizer only, rapid accumulation time of nitrogen (N) and potassium (K) was 7 days longer resulting from SAP addition. The maximum daily N and K accumulations in the fertilized seedlings increased by 9.31 and 10.44 %, respectively, whereas those of the unfertilized seedlings did not differ significantly. SAP addition had little effect on phosphorous (P) uptake, except for an increase in the maximum daily P accumulation under fertilized conditions. The shoot and root of P. pinaster with SAP had 8.61 and 13.70 % higher yields, respectively, than those that received fertilizer only. Compared with fertilizer only, SAP addition with fertilizer increased the N and K contents by 7.15 and 10.04 %, respectively, whereas the P content did not differ significantly. Under fertilized conditions, N, P, and K uptake increased by 17.17, 10.13, and 20.33 %, respectively, from SAP addition. Hence, SAP could be used as a nutrient absorption enhancer (mainly N and K) in forest container seedlings, aside from being a water absorbent material.

Influence of the environment on swelling of hydrophilic polymers

The influence of water activity on swelling of cross-linked hydrophilic polymers in electrolyte solutions of various concentrations was studied. A heterophase model was proposed to explain the polymer swelling. It was shown that the change in polymer swelling deals with different water sorption, and is described by water vapour sorption isotherm. At the same time, the volume of external solution taken up by polymer at swelling is constant and independent of concentration of the solution. Three models describing the structure of polymer gels were suggested and discussed on the base of the obtained results.

Mild Oxidation of Thiofunctional Polymers to Cytocompatible and Stimuli‐Sensitive Hydrogels and Nanogels

Nanogels consist of three dimensionally cross-linked hydrophilic polymer chains and can thus be easily modified through functionalization of the polymeric building blocks, for example to yield stimuli-sensitive materials. For drug transport and intracellular release, redox-sensitive systems are especially of interest, as the intracellular space is reductive. In this study, parameters that allow preparation of nanogels with tunable size between 150 and 350 nm are systematically evaluated and identified. Most importantly, a new and mild oxidation catalyst, alloxan, is introduced for the preparation of the nanogels. This broadens the range of possible payloads to more-sensitive molecules. Particle stability, degradation in cytosolic conditions, and cytocompatibility in concentrations up to 10 mg · mL(-1) are demonstrated.