Hydrophobically modified hydrogels containing azoaromatic cross-links: swelling properties, degradation in vivo and application in drug delivery

Hydrogels based on n-alkyl methacrylate esters (n-AMA) of various chain lengths, acrylic acid, and acrylamide cross-linked with 4,4-di(methacryloylamino)azobenzene were synthesized. The equilibrium swelling degree of the hydrogels in buffered solutions at pH 7.4 was shown to be very low in the pH range of the stomach. The entire swelling processes of the gels in the gastrointestinal tract were mainly dependent on those in the small intestine. In the buffered solution of pH 7.4 the diffusion of water into the gel slabs was discussed on the stress relaxation model of polymer chains. The results obtained are in good agreement with Schott's second-order diffusion kinetics. The biodegradability in vivo of their azobenzene cross-linking groups as well as the mechanism of degradation by cecal bacteria was studied. The gels are stable in the stomach but degradable by ananerobes present in the colon. The extent of degradation was considerably related to the equilibrium degree of swelling. The factors influencing the swelling degree were shown to influence the in vivo degradation of the gels. By changing these factors such as the degree of cross-linking, the length and content of the n-AMA side chains, it is possible to control both the degree of swelling and the degradation of the hydrogels.     

Mussel-mimicking sulfobetaine-based copolymer with metal tunable gelation,self-healing and antibacterial capability

In the present study, the sulfobetaine-based copolymer bearing a dopamine functionality showed gel formation adjusted by the application of metal salts for gelation and various values of pH. Normally, the liquid-like solution of the sulfobetaine-based copolymer and metal cross-linkers is transformed to a gel-like state upon increasing the pH values in the presence of Fe³⁺ and Ti³⁺. Metal-induced coordination is reversible by means of the application of EDTA as a chelating agent. In the case of Ag⁺ ions, the gel is formed through a redox process accompanied with the oxidative coupling of the dopamine moieties and Ag⁰ particle formation. Mussel-mimicking and metal-dependent viscoelastic properties were observed for Fe³⁺, Ti³⁺, and Ag⁺ cross-linking agents, with additionally enhanced self-healing behavior in comparison with the covalently cross-linked IO₄⁻ analogues. Antibacterial properties can be achieved both in solution and on the surface using the proper concentration of Ag⁺ ions used for gelation; thus, a tunable amount of the Ag⁰ particles are formed in the hydrogel. The cytotoxicity was elucidated by the both MTT assay on the NIH/3T3 fibroblast cell line and direct contact method using human dermal fibroblast cell (F121) and shows the non-toxic character of the synthesized copolymer.     

The remarkable role of hydrogen bond,halogen, and solvent effect on self-healing supramolecular gel

Self-healing supramolecular gels of low-molecular-weight (LMW) molecules are smart soft materials; however, the development of self-healing LMW gelator is still a challenging task because of the lack of in-depth studies about self-healing mechanisms of LMW gels and the solvent effect on gel properties. Therefore, herein a different perspective was used to study a family of D-gluconic acetal-based gelators with variable structural fragments in 14 different solvents, and a more detailed understanding of self-assembly and self-healing mechanism of supramolecular gels was attained. Based on the critical gelation concentration, phase transition temperature, and rheological data, A8 bearing an amide group in side chain and two chlorine atoms linked to benzene ring was found to be an outstanding gelator, which could form gels with good self-healing ability in a variety of solvents. Interestingly, A8 gel formed in n-BuOH demonstrates high transparency, good mechanical strength, self-supporting behavior, and great self-healing ability from mechanical damage. Based on the Fourier transform infrared spectroscopy, nuclear magnetic resonance spectroscopy, X-ray photoelectron spectroscopy, X-ray diffraction, and theoretical calculation analysis, the self-assembly and self-healing mechanisms of A8 gel were proposed, indicating that a combination of hydrogen bonding and halogen effect was responsible for the efficient self-healing behavior of supramolecular gel. Furthermore, the analysis of solvent parameters indicated that the dispersion force of solvent favored gelators to self-assemble, hydrogen bonding donor ability of solvent mainly affected the formation of one-dimensional assembly, and hydrogen bonding receptor ability and polarity of solvent mainly influenced the supramolecular interactions among assemblies, significantly intervening the self-healing ability of gels. Overall, this study provides a new perspective to the understanding of gelator structure–property correlation in solvents and sheds light for future development of self-healing supramolecular gels.     

Highly stretchable and self-healing hydrogels based on poly(acrylic acid) and functional POSS

Herein, we present a novel way for the production of self-healing hydrogels with stretch beyond 4200% than their initial length and relatively high tensile strength(0.1?0.25 MPa). Furthermore, the hydrogel was insensitive to notch. Even for the samples containing V-notches, a stretch of 2300% was demonstrated. The hydrogels were developed by in situ crosslinking of the self-assembled colloidal poly(acrylic acid)(PAA)/functionalized polyhedral oligomeric silsesquioxane(POSS) micelles. This was achieved by the addition of functionalized polyhedral oligomeric silsesquioxane with tertiary amines and hydroxyls(POSS-AH) into the PAA reaction solution. The POSS-AH led to micellar growth, then the dualcrosslinked network was constructed. One type of crosslink was formed by hydrogen-bonding and ionic interactions between PAA chains and POSS-AH, the other type of crosslink was formed by covalent bonds between PAA and bis(N,N'-methylenebis-acrylamide).     

Selection of healing agents for a vascular self-healing application

To increase the durability and reliability of thermosets, self-healing via a vascular network, is developed. A judicious choice of healing agents proves to be necessary to achieve the best recovery of properties. Four low viscosity two-component epoxy-amine healing systems were compared, to check which glass transition temperature range would be best to recover mechanical properties (T_g ranging from −8 to 68 °C). Interdiffusion experiments show that all systems react sufficiently slowly at room temperature to allow interdiffusion of epoxy and amine over more than 1 mm before the diffusion is stopped by vitrification. Swelling tests revealed that most of the selected healing agents diffuse into the surrounding matrix and swell it. This might be beneficial for crack closure and improved adhesion between healing system and matrix. Flexural tests demonstrated that, the higher the glass transition temperature of the fully cured healing system, the higher the healing capability.     

Preparation and characterization of new hydrogels based on hyaluronic acid and α,β-polyaspartylhydrazide

Hyaluronic acid (HA) has been crosslinked with α,β-polyaspartylhydrazide (PAHy). The crosslinking reaction has been performed in acidic medium in the presence of various amounts of N-ethyl-N′-(3-dimethylaminopropyl)-carbodiimide hydrochloride (EDC). All obtained samples have been characterized by FT-IR analysis and swelling measurements in double distilled water that have confirmed the occurrence of a chemical linkage between two polymers and the affinity towards aqueous medium of HA-PAHy networks, respectively.In vitro degradation assays have been performed in simulated physiological conditions as well as in the presence of hyaluronidase. Experimental data evidenced that HA-PAHy samples undergo a poor chemical and a reduced enzymatic degradation unlike native HA.     

Designing of pH-responsive ketorolac tromethamine loaded hydrogels of alginic acid: Characterization,in-vitro and in-vivo evaluation

pH-responsive hydrogels based on alginic acid grafted with acrylic acid and ethylene glycol dimethylacrylate in the presence of ammonium persulfate were developed for controlled delivery of Ketorolac tromethamine. The alginic acid based hydrogels were prepared by free radical polymerization technique. Increase in gel fraction was observed with the increase in alginic acid, acrylic acid, and ethylene glycol dimethylacrylate content. The dynamic swelling and drug release studies were conducted at two different pH values (pH 1.2 and 7.4). Maximum swelling and drug release were observed at pH 7.4. The characterization of prepared hydrogels was carried out by using Fourier transform infrared spectroscopy, thermogravimetric analysis, differential scanning calorimetry, powder x-ray diffraction, and scanning electron microscopy. Similarly, in-vivo study was performed on rabbits and greater plasma drug concentration was achieved by fabricated hydrogels as compared to drug solution and commercial product Keten. Conclusively, the fabricated hydrogels can be considered as a potential candidate for controlled delivery of Ketorolac tromethamine.     

A combined redox-competition and negative-feedback SECM study of self-healing anticorrosive coatings

In this paper, the long-term anticorrosive efficiency of a damaged self-healing coating is studied for the first time using scanning electrochemical microscopy (SECM). In the study an epoxy-coating with embedded-capsules containing a silyl-ester is employed. The properties of the silyl-ester as a healing-agent for the protection of AA2024-T3 were evaluated by complementary SECM experiments operating in negative-feedback and redox-competition modes. The experimental approach here presented allowed for monitoring the early-stages of corrosion activity and subsequent healing mechanisms offered by the release of silyl-ester into a relatively large coating defect. This result was observed by detecting the transition of the oxygen reduction response from a redox-competition mode to a negative-feedback behavior. These measurements demonstrated that the silyl-ester is released efficiently after capsules break upon coating damage, covering relatively large areas and gradually healing the damaged-site hindering the corrosion processes and providing an effective protection for at least one month of immersion in chloride solution.     

Synthesis and release profile analysis of thermo-sensitive albumin hydrogels

Novel thermo-responsive hydrophilic microspheres were prepared by free radical polymerization of methacrylate bovine serum albumin and N-isopropylacrylamide, as cross-linker and functional monomer, respectively. The incorporation of monomers in the network was confirmed by infrared spectroscopy, while the network density and shape of hydrogels strictly depend on concentration of monomers in the polymerization feed. The thermal analyses showed negative thermo-responsive behavior with pronounced water affinity of microspheres at temperature lower than lower critical solution temperature (LCST). The in vitro release studies of drug-loaded thermo-sensitive hydrogels were performed. Experimental data showed, for the copolymers with functional monomer/cross-linker ratio ≤ 1, a predominant drug release in the collapsed state, while the copolymers with functional monomer/cross-linker ratio > 1 showed prominent drug release in the swollen state. Below the hydrogel LCST, drug release through the swollen polymeric networks was observed, while a squeezing-out effect at temperature above the LCST was predominant.     

1,8-Naphthalimide-based colorimetric and fluorescent sensor for recognition of GMP,TMP, and UMP and its application in in vivo imaging

In this study, a series of 1,8-naphthalimide-based analogs were developed for fluorescence imaging of nucleotides in Caenorhabditis elegans. In DMSO, compound 1 proved to be an effective and selective colorimetric and fluorescent sensor for recognition of GMP, TMP, and UMP over other structurally similar nucleotides. Among all the tested nucleotides, only the addition of GMP, TMP, and UMP resulted in a fluorescence color change from blue to brown with a fluorescence enhancement of more than 600-fold, with the colorless solution turning brown. NMR spectroscopic titration, theoretical calculations, and spectral tests performed using various solvent compositions confirmed that compound 1 formed multiple hydrogen bonds with the related base groups in the nucleotide. Compound 1 demonstrated its utility as a fluorescent chemosensor for detecting GMP, TMP, and UMP in in vivo imaging of GMP, TMP, and UMP in C. elegans.     

Synthesis of polyacrylamide/polyurethane hydrogels by latex IPN and AB crosslinked polymers

Interpenetrating polymer network (IPN) and AB crosslinked polymer (ABCP) hydrogels composed of polyacrylamide (PAAm) and polyurethane (PU) have been synthesized as function of degree of polymerization of PU prepolymer, crosslink density of PAAm domain, and gel composition. Both PAAm/PU IPN and ABCP gels gave synergistic effects in terms of density showing positive deviation from the linear additivity. As a result of this, the strength of swollen gel increased over approximately two times with a small addition of flexible PU (10–20%) to the rigid PAAm.     

The effect of solvent composition on swelling and shrinking properties of poly(acrylamide-co-itaconic acid) hydrogels

The peculiarities of the equilibrium swelling ratio and swelling-shrinking kinetics of polyelectrolyte copolymeric hydrogels consisting of acrylamide and itaconic acid (AAm/IA) have been studied in water/nonsolvent (acetone, methanol, ethanol and 1-butanol) mixtures as a function of solvent composition and IA content in the hydrogel. The phase transition of these hydrogels was generated by changing the solvent composition by progressive substitution of water by the nonsolvent. For all P(AAm/IA) hydrogels, the form of the shrinking curves was determined to be strongly dependent on the type of the nonsolvent used. The rate of shrinking of these hydrogels increased in the order 1-butanol < ethanol < methanol < acetone.     

Micro- and Nanosensors,Recent Developments and Features: A Minireview

Recent developments on micro and nanosensors are discussed. The nano- and micro magnitude orders are not only related to the entire active area of the electrode, but also to the sizes of the active substances/matrix of the electrodes' membrane. Nowadays, Nanowires are the trend in nanosensors technology that permit the integration of nanosensors in (bio)chips and in devices for in vivo analysis.     

Characterization of nitrate ions adsorption and diffusion in P（DMAEMA/HEMA） hydrogels

In this work, the adsorption and diffusion behavior of nitrate ions into polycationic P（DMAEMA/HEMA） hydrogels is analyzed. Experimental results indicated that nitrate ions can be removed efficiently from aqueous solutions. Adsorption isotherm of gels was well according to the Langmuir and Langmuir-Freundlich models. At the same time, the diffusion behavior of nitrate ions from P（DMAEMA/HEMA） hydrogels was investigated. The diffusion coefficients are strongly influenced by the changes of temperature and pH value of solutions. At the same time, D does not depend on the gels cross-linking ratio and initial solute concentration.     

Blood chemical components analysis of honeysuckle and formulation of xanthan gum/starch-based (PVA-co-AA) hydrogels for controlled release

Honeysuckle is a commonly used Chinese medicine for treating intestinal inflammation and other diseases. Compounds that are absorbed into the blood produce pharmacodynamic effects. However, it is still unclear which compounds in honeysuckle are absorbed into the blood. Thus, the purpose of this study was to investigate the composition and in vivo absorption of active components in honeysuckle in male Sprague-Dawley rats, and develop a controlled release hydrogel system. UPLC-LTQ-Orbitrap-MS was used to determine the active ingredients of honeysuckle in vitro and in vivo. A total of 80, out of which 42 components were found to be absorbed into the blood, which includes flavonoids, iridoids, organic acids and other compounds. FTIR analysis confirmed crosslinking between hydrogel content and drug loading, and TGA and DSC analysis indicated a high thermal stability. XRD analysis showed a decrease in crystallinity following crosslinking, and SEM revealed an irregular and hard surface. The maximum swelling and drug release were observed at pH 7.4 as compared to pH 1.2. The identified blood components can be used to determine Q-markers, while the prepared hydrogels can serve as an effective and promising carrier for the controlled release of honeysuckle extracts.     

Self-Healing Polymer Composites: Prospects,Challenges, and Applications

Self-healing polymer composites possess the inherent ability to heal the damage event autonomically or non-autonomically with external intervention. These advanced materials can be commercialized if the challenges and limitations of different self-healing mechanisms are well known and considered. These include capsule-based healing systems, vascular healing systems, and intrinsic healing systems. To date, most of the reviews have studied and reported on different self-healing mechanisms including their response to impact, fatigue, and corrosion tests. This review focuses mostly on extrinsic and intrinsic self-healing polymer composites which have been reported during the past five years by comparing their healing efficiency, advantages, and challenges in the prospect of their future development as well as their possible applications across various industries such as aerospace, automobile, coating, electronics, energy, etc.     

Surface modification and property analysis of biomedical polymers used for tissue engineering

The response of host organism in macroscopic, cellular and protein levels to biomaterials is, in most cases, closely associated with the materials’ surface properties. In tissue engineering, regenerative medicine and many other biomedical fields, surface engineering of the bio-inert synthetic polymers is often required to introduce bioactive species that can promote cell adhesion, proliferation, viability and enhanced ECM-secretion functions. Up to present, a large number of surface engineering techniques for improving biocompatibility have been well established, the work of which generally contains three main steps: (1) surface modification of the polymeric materials; (2) chemical and physical characterizations; and (3) biocompatibility assessment through cell culture. This review focuses on the principles and practices of surface engineering of biomedical polymers with regards to particular aspects depending on the authors’ research background and opinions. The review starts with an introduction of principles in designing polymeric biomaterial surfaces, followed by introduction of surface modification techniques to improve hydrophilicity, to introduce reactive functional groups and to immobilize functional protein molecules. The chemical and physical characterizations of the modified biomaterials are then discussed with emphasis on several important issues such as surface functional group density, functional layer thickness, protein surface density and bioactivity. Three most commonly used surface composition characterization techniques, i.e. ATR-FTIR, XPS, SIMS, are compared in terms of their penetration depth. Ellipsometry, CD, EPR, SPR and QCM's principles and applications in analyzing surface proteins are introduced. Finally discussed are frequently applied methods and their principles to evaluate biocompatibility of biomaterials via cell culture. In this section, current techniques and their developments to measure cell adhesion, proliferation, morphology, viability, migration and gene expression are reviewed.     

Improved self-healing performance of polymeric nanocomposites reinforced with talc nanoparticles (TNPs) and urea-formaldehyde microcapsules (UFMCs)

The present work reports the self-healing performance of the epoxy based polymeric nanocomposite coatings containing different concentrations (1 and 3 wt%) of talc nanoparticles (TNPs) modified with sodium nitrate (NaNO₃), and a fixed amount (5 wt%) of urea-formaldehyde microcapsules (UFMCs) encapsulated with linseed oil (LO). The polymeric nanocomposites were developed, coated on polished steel substrates, and their structural, thermal, and self-healing characteristics were investigated using various techniques. The successful loading (~wt 10%) of NaNO₃ into TNPs, which can be ascribed to the involvement of physio-chemical adsorption mechanism, is validated and proceeds without altering the TNPs parent lamellae structure. The performed tests elucidated that the self-release of the corrosion inhibitor (NaNO₃) from TNPs is sensitive to the pH of the solution and immersion time. In addition, the release of the linseed oil (self-healing agent) from UFMCs in response to the external damage was found to be a time-dependent process. The superior self-healing and corrosion inhibition performance of the protective polymeric nanocomposites coatings containing 3 wt% TNPs and UFMCs/LO are proven using the electrochemical impedance spectroscopy (EIS) studies. A careful selection of smart carriers, inhibitor, and self-healing agent compatible with polymeric matrix has enabled to attain decent self-healing and convincing corrosion inhibition efficiency of 99.9% and 99.5%, respectively, for polymeric nanocomposites coatings containing 3 and 1 wt% TNPs, making them attractive for many industrial applications.     

Dual-responsive shape memory and self-healing ability of a novel copolymer from epoxy/cashew nut shell liquid and polycaprolactone

In this work, the blends of epoxy (EP) and polycaprolactone (PCL) with a bio-based curing agent, viz. cashew nut shell liquid (CNSL) were studied for their dual-responsive shape memory and self-healing behaviors. The suitable EP/CNSL weight ratio was observed at 70/30. The increase of PCL content up to 20 wt% in EP-CNSL matrix significantly enhanced the shape memory response to both thermal and chemical stimuli. All specimens showed 100% thermo-responsive shape recovery and the recovery time decreased with increasing PCL content. In the case of chemo-responsive shape memory, the immersion times spent for 100% shape recovery in water and methanol substantially decreased when PCL was added. Moreover, after thermal treatment, the EP-CNSL matrix with 20 wt% PCL showed significant self-healing ability with high tensile strength recovery at 93.70%. The EP-CNSL/PCL copolymer could be a promising alternative bio-related smart material for various applications such as dual-activated sensors and coatings with self-healing ability.     

Synthesis and characterization of new hydrogels through copolymerization of N-acryloyl-tris-(hydroxymethyl)aminomethane and different crosslinking agents

In this study, new hydrogels in rod shape were prepared from N-acryloyl-tris-(hydroxymethyl)aminomethane (NAT) using three different crosslinking agents: poly(2-methyl-2-oxazoline) bismacromonomer (BM), ethylene glycol dimethacrylate (EGDMA) and N,N′-methylenebisacrylamide (BIS). Dimethylformamide (DMF) was used as solvent and 2,2′-azobisisobutyronitrile (AIBN) as initiator. Polymeric matrices with different properties were obtained by free radical polymerization by changing the crosslinker (BM, EGDMA or BIS) or the concentration of BM. The hydrogel structures were characterized by high resolution magic angle spinning (HRMAS) NMR technique. Swelling experiments and rheological studies were used to test the water absorption capacity and viscoelastic properties of the hydrogels, respectively. For a given NAT/crosslinking agent molar ratio, the hydrogel synthesized with BM displays higher water absorptive capacity and larger range of linear viscoelasticity than those synthesized with BIS or EGDMA. The relatively larger hydrophilic character of the former and the lower crosslinking density generated by the longer molecules of BM might be the cause of this behavior. The results also reveal that water diffuses into the network following a non-Fickian mechanism. This is concluded from the value of the diffusion exponent n, which is higher than 0.50. The elastic modulus and the equilibrium water content (EWC) measurements suggest that these materials may have potential application as biomaterials.