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Design, Characterization, and Biocompatibility of Modular Biopolymer-Based Single- and Double-Cross-Linked Networks Hydrogels
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Increasing interest in the utilization of hydrogels in various areas of biomedical sciences ranging from biosensing and drug delivery to tissue engineering has necessitated the synthesis of these materials using efficient and benign chemical transformations. In this regard, the advent of “click” chemistry revolutionized the design of hydrogels and a range of efficient reactions was utilized to obtain hydrogels with increased control over their physicochemical properties. The ability to apply the “click” chemistry paradigm to both synthetic and natural polymers as hydrogel precursors further expanded the utility of this chemistry in network formation. In particular, the ability to integrate clickable handles at predetermined locations in polymeric components enables the formation of well-defined networks. Although, in the early years of “click” chemistry, the copper-catalyzed azide-alkyne cycloaddition was widely employed, recent years have focused on the use of metal-free “click” transformations, since residual metal impurities may interfere with or compromise the biological function of such materials. Furthermore, many of the non-metal-catalyzed “click” transformations enable the fabrication of injectable hydrogels, as well as the fabrication of microstructured gels using spatial and temporal control. This review article summarizes the recent advances in the fabrication of hydrogels using various metal-free “click” reactions and highlights the applications of thus obtained materials. One could envision that the use of these versatile metal-free “click” reactions would continue to revolutionize the design of functional hydrogels geared to address unmet needs in biomedical sciences.
Most tough hydrogels are reinforced by introducing energy dissipation mechanisms, but simultaneously realizing a high toughness and low hysteresis is challenging because the energy dissipation structure cannot recover rapidly. In this work, high mechanical performance highly entangled double network hydrogels without energy dissipation structure are fabricated, in which physical entanglements act as the primary effective crosslinking in the first network. This sliding entanglement structure allows the hydrogel network to form a highly uniform oriented structure during stretching, resulting in a high tensile strength of ~3 MPa, a fracture energy of 8340 J m⁻² and a strain-stiffening capability of 47.5 in 90% water content. Moreover, almost 100% reversibility is obtained in this hydrogel via energy storage based on entropy loss. The highly entangled double network structure not only overcomes the typical trade-off between the high toughness and low hysteresis of hydrogels, but more importantly, it provides an insight into the application of entanglement structures in high-performance hydrogels.
These authors contributed equally to this work. Abstract: The anionic polymer sodium alginate, a linear copolymer of guluronic and mannuronic acids, is primarily present in brown algae. Copolymers are used in the sodium alginate preparation process to confer on the material strength and flexibility. Micelles and other polymeric nanoparticles are frequently made using the triblock copolymer Pluronic ® F-127. The purpose of the present study is to determine the effect of sodium alginate's viscosity (low and medium) and the presence of Pluronic ® F-127 micelles on the swelling behavior of the prepared pure beads and those loaded with Pluronic ® F-127 micelles. The Pluronic ® F-127 nanomicelles have a size of 120 nm. The swelling studies were carried out at pH = 1.2 (simulated gastric fluid-SGF) for two hours and at pH = 6.8 (simulated intestinal fluid-SIF) for four more hours. The swelling of both low-and medium-viscosity alginate beads was minor at pH = 1.2, irrespective of the use of Pluronic ® F-127 nanomicelles. At pH = 6.8, without Pluronic ® F-127, the beads showed an enhanced swelling ratio for the first four hours, which was even higher in the medium-viscosity alginate beads. With the addition of Pluronic ® F-127, the beads were dissolved in the first and second hour, in the case of the low-and medium-alginate's viscosity, respectively. In other words, the behavior of the mixed hydrogels was the same during the swelling experiments. Therefore, the presence of Pluronic ® F-127 nanomicelles and medium-viscosity sodium alginate leads to a higher swelling ratio. A model drug, acetyl salicylic acid (ASA), was also encapsulated in the mixed beads and ASA's release studies were performed. In conclusion, the prepared systems, which are well characterized, show potential as delivery platforms for the oral delivery of active pharmaceutical ingredients and biopharmaceuticals.
Hydrogels have been developed for different biomedical applications such as in vitro culture platforms, drug delivery, bioprinting and tissue engineering. Enzymatic cross-linking has many advantages for its ability to form gels in situ while being injected into tissue, which facilitates minimally invasive surgery and adaptation to the shape of the defect. It is a highly biocompatible form of cross-linking, which permits the harmless encapsulation of cytokines and cells in contrast to chemically or photochemically induced cross-linking processes. The enzymatic cross-linking of synthetic and biogenic polymers also opens up their application as bioinks for engineering tissue and tumor models. This review first provides a general overview of the different cross-linking mechanisms, followed by a detailed survey of the enzymatic cross-linking mechanism applied to both natural and synthetic hydrogels. A detailed analysis of their specifications for bioprinting and tissue engineering applications is also included.
Hydrogels with a three-dimensional network structure are particularly outstanding in water absorption and water retention because water exists stably in the interior, making the gel appear elastic and solid. Although traditional hydrogels have good water absorption and high water content, they have poor mechanical properties and are not strong enough to be applied in some scenarios today. The proposal of double-network hydrogels has dramatically improved the toughness and mechanical strength of hydrogels that can adapt to different environments. Based on ensuring the properties of hydrogels, they themselves will not be damaged by excessive pressure and tension. This review introduces preparation methods for double-network hydrogels and ways to improve the mechanical properties of three typical gels. In addition to improving the mechanical properties, the biocompatibility and swelling properties of hydrogels enable them to be applied in the fields of biomedicine, intelligent sensors, and ion adsorption.
Coating the solid dosage form, such as tablets, is considered common, but it is a critical process that provides different characteristics to tablets. It increases the value of solid dosage form, administered orally, and thus meets diverse clinical requirements. As tablet coating is a process driven by technology, it relies on advancements in coating techniques, equipment used for the coating process, evaluation of coated tablets, and coated material used. Although different techniques were employed for coating purposes, which may be based on the use of solvents or solvent-free, each of the methods used has its advantages and disadvantages, and the techniques need continued modification too. During the process of film coating, several inter-and intra-batch uniformity of coated material on the tablets is considered a critical point that ensures the worth of the final product, particularly for those drugs that contain an active medicament in the coating layer. Meanwhile, computational modeling and experimental evaluation were actively used to predict the impact of the operational parameters on the final product quality and optimize the variables in tablet coating. The efforts produced by computational modeling or experimental evaluation not only save cost in optimizing the coating process but also saves time. This review delivers a brief review on film coating in solid dosage form, which includes tablets, with a focus on the polymers and processes used in the coating. At the end, some pharmaceutical applications were also discussed.
The advances in polymer chemistry research have revolutionized the field of smart materials and biomedical. Polyurethanes (PUs) are a versatile polymer class with diverse structure, morphology, and behavior under various conditions deemed suitable for many functional and intelligent responses. Owing to their biocompatibility, biodegradability, excellent mechanical strength, tailorable chemical, and physical forms, PU has drawn significant research attention in recent times for a wide range of applications. Herein, this review paper outlines PU's recent advances in specific applications encompassing functional textiles, intelligent functionality and medical usage. This article contains a comprehensive review of recent developments and research works concerning PU's direct involvement as coatings, 3D objects, or composite parts to add novel purpose to the textile substrates, smart objects, or medical applications. Commencing with PU's application for the waterproof breathable textiles, the review further explores recent research where PU was incorporated as a phase change material and protective clothing. This review further delves innovative functionalities and responsiveness of the polymer triggered by various stimuli. It ends with an inclusive review of PU's different forms of application concerning medical devices and activities. Finally, perspectives on future challenges and new research opportunities are also presented and discussed.
The rapid and selective detection of bacterial contaminations and bacterial infections in a non-laboratory setting using advanced sensing materials holds the promise to enable robust point-of-care tests and rapid diagnostics for applications in the medical field as well as food safety. Among the various possible analytes, bacterial enzymes have been targeted successfully in various sensing formats. In this current work, we focus on the systematic investigation of the role of surface area on the sensitivity in micro- and nanostructured autonomously reporting sensing hydrogel materials for the detection of bacterial enzymes. The colorimetric sensing materials for the detection of β-glucuronidase (ß-GUS) from Escherichia coli (E. coli) were fabricated by template replication of crosslinked pullulan acetoacetate (PUAA) and by electrospinning chitosan/polyethylene oxide nanofibers (CS/PEO NFs), both equipped with the chromogenic substrate 5-bromo-4-chloro-3-indolyl-β-D-glucuronide. The investigation of the dependence of the initial reaction rates on surface area unveiled a linear relationship of rate and thereby time to observe a signal for a given concentration of bacterial enzyme. This knowledge was exploited in nanoscale sensing materials made of CS/PEO NFs with diameters of 295 ± 100 nm. Compared to bulk hydrogel slabs, the rate of hydrolysis was significantly enhanced in NFs when exposed to bacteria suspension cultures and thus ensuring a rapid detection of living E. coli that produces the enzyme β-GUS. The findings afford generalized design principles for the improvement of known and novel sensing materials towards rapid detection of bacteria by nanostructuring in medical and food related settings.
Growing interest in the use of natural organic compounds in the production of green concrete with the use of plasticizers has been particularly noticeable in the literature of recent decades. Starch is an attractive material due to its abundance, the low cost of sourcing it, and its biodegradability, biocompatibility, and susceptibility to modification. The objective of the study was to evaluate the effect of starch hydrolysate additives on the physicochemical properties of cement composites and concrete. Compressive strength tests and cement slurry rheology measurements were carried out for water–cement ratios from 0.40 to 0.50 and for amounts of added dextrin from 0.0 to 0.7% in relation to the cement weight. The dextrins used were characterized in terms of their viscosity, polymerisation degree, and surface activity in air/water systems. Conducted research indicates that even the minimum content of dextrin increases the fluidization of cement mixes (the flow diameter increased by 67.5% compared with the mixture without the admixture), enables the reduction of mixing water, and contributes to the compressive strength of cement mortars. A further decrease in the w/c ratio to the value of 0.40 resulted in an increase in the strength value of up to 67.9 MPa, which provided a 40% increase in strength. The degree of the polymerisation of added dextrin is seen as having an effect on the physical parameters of the cement mortar; the shorter the polymer chain of the studied dextrin, the more packed the adsorbent layer, and the greater the flow diameter of the cement mortar.
For the practical use of synthetic hydrogels as artificial biological tissues, flexible electronics, and conductive membranes, achieving requirements for specific mechanical properties is one of the most prominent issues. Here, we demonstrate superstrong, superstiff, and conductive alginate hydrogels with densely interconnecting networks implemented via simple reconstructing processes, consisting of anisotropic densification of pre-gel and a subsequent ionic crosslinking with rehydration. The reconstructed hydrogel exhibits broad ranges of exceptional tensile strengths (8–57 MPa) and elastic moduli (94–1,290 MPa) depending on crosslinking ions. This hydrogel can hold sufficient cations (e.g., Li+) within its gel matrix without compromising the mechanical performance and exhibits high ionic conductivity enough to be utilized as a gel electrolyte membrane. Further, this strategy can be applied to prepare mechanically outstanding, ionic-/electrical-conductive hydrogels by incorporating conducting polymer within the hydrogel matrix. Such hydrogels are easily laminated with strong interfacial adhesion by superficial de- and re-crosslinking processes, and the resulting layered hydrogel can act as a stable gel electrolyte membrane for an aqueous supercapacitor. Specific mechanical properties are one of the most important issues for application of synthetic hydrogels as biological tissue, flexible electronics or in conductive membranes. Here, the authors demonstrate that a reconstruction process consisting of anisotropic densification of pre-gel and subsequent ionic crosslinking and rehydration leads to strong, stiff, and conductive alginate hydrogels with densely interconnecting networks.
Modified alginates have a wide range of applications, including in the manufacture of dressings and scaffolds used for regenerative medicine, in systems for selective drug delivery, and as hydrogel materials. This literature review discusses the methods used to modify alginates and obtain materials with new or improved functional properties. It discusses the diverse biological and functional activity of alginates. It presents methods of modification that utilize both natural and synthetic peptides, and describes their influence on the biological properties of the alginates. The success of functionalization depends on the reaction conditions being sufficient to guarantee the desired transformations and provide modified alginates with new desirable properties, but mild enough to prevent degradation of the alginates. This review is a literature description of efficient methods of alginate functionalization using biologically active ligands. Particular attention was paid to methods of alginate functionalization with peptides, because the combination of the properties of alginates and peptides leads to the obtaining of conjugates with properties resulting from both components as well as a completely new, different functionality.
Hydrogels are promising candidates for recapitulation of the native extracellular matrix (ECM), yet recreating molecular and spatiotemporal complexity within a single network remains a challenge. Double network (DN) hydrogels are a promising step towards recapitulating the multicomponent ECM and have enhanced mechanical properties. Here, we investigate DNs based on dynamic covalent and covalent bonds to mimic the dynamicity of and enable biofabrication. We also investigate the spatiotemporal molecular attachment of a bioactive adhesive peptide within the networks. Using oxidized alginate (dynamic network, Schiff base) and polyethylene glycol diacrylate (static network, acrylate polymerization) we find an optimized procedure, where the dynamic network is formed first, followed by the static network. This initial dynamically cross-linked hydrogel imparts self-healing, injectability, and 3D printability, while the subsequent DN hydrogel improves the stability of the 3D gels and imparts toughness. Rheology and compression testing show that the toughening is due to the combination of energy dissipation (dynamic network) and elasticity (static network). Furthermore, where we place adhesive sites in the network matters; we find distinct differences when tripeptide Arg-Gly-Asp (RGD) is attached to the different networks. This DN strategy bring us closer to understanding and recreating the complex multicomponent ECM—pushing us past a materials view of cell adhesion—while enabling injectabiltiy and printing of tough hydrogels.
Abstract
Novel biocompatible and brush copolymers have been developed for cancer treatment using its controlled drug-release potential. Polyurethane graft on linear dextrin has been synthesized to control the hydrophilic-hydrophobic balance for regulated drug delivery. The properties of the graft copolymers have been tuned through graft density. The prepared grafts are thermally stable and mechanically strong. An injectable hydrogel has been developed by embedding the drug-loaded brush copolymers in methyl cellulose to better control the release for a prolonged period, importantly by keeping the drug release at a constant rate. Cellular studies indicate the biocompatible nature of the brush copolymers whose controlled and slow release of drug exhibit significant cytotoxic effects on cancer cells. Endocytosis of drug tagged contrast agent indicates greater transport of biologically active material inside cell as observed through cellular uptake studies. In vivo studies on melanoma mice exhibit the real efficacy of the controlled drug release from the injectable hydrogel with significant melanoma suppression without any side effects as opposed to severe toxic effects observed in conventional chemotherapy. Special application method of drug-loaded hydrogel just beneath the tumor makes this system incredibly effective through confinement. Thus, brush copolymer injectable hydrogel is a promising vehicle for control release of drug for cancer treatment in future.
Polysaccharides are essential macromolecules which almost exist in all living forms, and have important biological functions , they are getting more attention because they exhibit a wide range of biological and pharmacological activities, such as anti-tumour, immunomodulatory, antimicrobial, antioxidant, anticoagulant, antidiabetic, antiviral, and hypoglycemia activities, making them one of the most promising candidates in biomedical and pharmaceutical fields. Polysaccharides can be obtained from many different sources, such as plants, microorganisms, algae, and animals. Due to their physicochemical properties, they are susceptible to physical and chemical modifications leading to enhanced properties, which is the basic concept for their diverse applications in biomedical and pharmaceutical fields. In this review, we will give insight into the most recent updated applications of polysaccharides and their potentialities as alternatives for traditional and conventional therapies. Challenges and limitations for polysaccharides in pharmaceutical utilities are discussed as well.
A novel approach was developed to prepare cellulose acetoacetate-graft-copolymers via horseradish peroxidase (HRP)-mediated polymerization. Cellulose acetoacetate (CAA), the macroinitiator, was obtained by transesterification between tert-butyl acetoacetate (t-BAA) and cellulose in ionic liquid. The CAA-graft-polyacrylamide (CAA-g-PAM) was synthesized using a ternary initiator system consisting of CAA, HRP and hydrogen peroxide (H2O2). The results of surface-initiated polymerization showed that the formation of free polymers could be inhibited in this process. The kinetics exhibited that this method is a powerful tool for obtaining graft copolymers. The effects of H2O2 concentration and reaction temperature were investigated to explore the optimal conditions for the process of enzymatic initiation. The synthesized copolymers were characterized by FT IR, NMR, TGA and elemental analysis to confirm the successful grafting of polyacrylamide chains onto the cellulose backbones. Furthermore, generality of the HRP-mediated graft polymerization approach was demonstrated using various monomers, including 2-hydroxyethyl methacrylate (HEMA), methyl methacrylate (MMA) and sulfobetaine methacrylate (SBMA). This efficient and robust strategy has great potential in fabrication of cellulose-based functional polymers.
Graphic abstract
Enzymatic grafting polymerization from cellulose acetoacetate
The present study sets out to the development of cationic graft copolymer, dextrin -g-PMETAC through grafting of 2-methacryloyloxyethyl trimethyl ammonium chloride (METAC) on to the dextrin polymer. Flocculation efficiency of this graft cationic copolymer was studied towards the biomass harvesting efficiency of three indigenous microalgal strains viz, Scenedesmus sp. CBIIT(ISM), Micractinium sp. NCS2 and Chlorella sp. NCQ. The results demonstrated that the synthesized copolymer was very effective in microalgal dewatering. The biomass harvesting efficiency of the dextrin-g-PMETAC for Scenedesmus sp. CBIIT(ISM), Micractinium sp. NCS2 and Chlorella sp. NCQ was 98.87 ± 0.17 %, 98.19 ± 0.22 % and 97.56 ± 0.28 % at optimized dosage of flocculant 25 ppm 35 ppm and 45 ppm respectively. Comparative study of biomass composition of polymer induced flocculated biomass and centrifuged biomass in terms of proteins, carbohydrates, lipids, and residual ash content indicated that the biomass harvesting through dextrin-g-PMETAC does not affect the characteristics of microalgal biomass. Based on the obtained results, dextrin-g-PMETAC could be considered as an efficient polymeric flocculant towards the harvesting of microalgae.
An efficient path to prepare cellulose acetoacetates is reviewed in detail. The biopolymer dissolved in N,N-dimethylacetamide-LiCl is allowed to react with 2,2,6-trimethyl-4H-1,3-dioxin-4-one at elevated temperatures without any catalyst. The procedure, which is briefly described in the literature (Marson and El Seoud in J Appl Polym Sci 74:1355–1360, 1999), utilizes simple to handle, commercially available compounds and requires only a short reaction time to obtain pure products that are promising starting materials for the design of advanced cellulose-based materials. Cellulose acetoacetates with degree of substitution of up to 1.84 can be obtained. A side reaction forming comb-like polymer structures was realized applying high molar ratio of cellulose to reagent (above 2 mol per mol) that was not known up to now. The hydrophobic cellulose acetoacetates can be transferred easily into nanoparticles with particle sizes ranging from 120 to 300 nm.
A new SiO2-alginate biocomposite was synthesized with improved mechanical properties, showing chelation
capability of divalent metal ions, especially Cu(II), through its carboxylic acid ends. The biocomposite was characterized
using scanning electron microscopy (SEM), Fourier-transform infrared (FTIR), and X-ray photoelectron spectroscopy
(XPS) techniques. The adsorption of copper(II) onto both H- and Ca-forms of sorbent was investigated as a
function of pH and contact time, and adsorption data were modeled with the aid of Langmuir and Freundlich isotherms.
The release of Ca(II) ions accompanying copper(II) binding was evaluated by selective surface complexation
concept involving ion-exchange. The IR spectra gave detailed information on complexation of carbonyl group with
copper ions and on the relative contribution of SiO2 involved in copper uptake. The adsorption edge of copper was
within the pH range 4.0-5.5, and the sorbent capacity was determined as 1.85 and 1.10mmolg−1 for H- and Ca-forms,
respectively.
A one-pot methodology was successfully developed to synthesize chiral imprinted silica nanospheres with hollow and mesoporous structures. These silica nanospheres demonstrated high capacity and chiral selectivity for L- or D- 3,4-dihydroxyphenylalanine (L- or D-DOPA) and possessed potency for L-DOPA controlled release.
Microencapsulation of cells by using biodegradable hydrogels offers numerous attractive features for a variety of biomedical applications including tissue engineering. This study highlights the fabrication of microcapsules from alginate-gelatin cross-linked hydrogel (ADA-GEL) and presents the evaluation of the physico-chemical properties of the new microcapsules which are relevant for designing suitable microcapsules for tissue engineering. Alginate di-aldehyde (ADA) was synthesized by periodate oxidation of alginate which facilitates crosslinking with gelatin through Schiff’s base formation between the free amino groups of gelatin and the available aldehyde groups of ADA. Formation of Schiff’s base in ADA-GEL and aldehyde groups in ADA was confirmed by FTIR and NMR spectroscopy, respectively. Thermal degradation behavior of films and microcapsules fabricated from alginate, ADA and ADA-GEL was dependent on the hydrogel composition. The gelation time of ADA-GEL was found to decrease with increasing gelatin content. Swelling ratio of ADA-GEL microcapsules of all compositions was significantly decreased, whereas the degradability was found to increase with increasing of gelatin ratio. Surface morphology of the ADA-GEL microcapsules was totally different to that of alginate and ADA microcapsules, observed by SEM. Two different buffer solutions (with and without calcium salt) have influence on the stability of microcapsules that drew a significant difference on gelatin release profile from ADA-GEL microcapsules in these two buffer solutions.
The colon is a main absorption site (nutrients and drugs) and a target for 7 oral therapeutic delivery. However, the latter is challenged by the fact that most drugs 8 degrade during transit in the gastrointestinal tract (GIT). Herein, we rationally designed a 9 universal controlled-release system based on cubosomes contained in microbial 10 nanocellulose capsules that enables oral administration and pH-triggered delivery of 11 bioactives. We show that the bicontinuous cubosome structure allows the simultaneous 12 incorporation of drugs with differing polarity or surface energy. Furthermore, the multidrug 13 cubosomes combined with the cellulosed carrier by in situ biofabrication is demonstrated as 14 a route toward multicomponent 3D capsules with added protection in the GIT. The 15 obtained capsules were subsequently coated with sodium alginate to enable responsiveness, 16 achieving dual cargo-controlled release and site-specific administration. In sum, we 17 successfully engineered pH-responsive, nontoxic microcapsules as a versatile platform for 18 colon-targeted multidrug delivery. 19
Polysaccharides are biodegradable, abundant, sustainable, and often benign natural polymers. The achievement of selective modification of polysaccharides is important for targeting specific properties and structures and will benefit future development of highly functional, sustainable materials. The synthesis of polysaccharides containing aldehyde or ketone moieties is a promising tool for achieving this goal because of the rich chemistry of aldehyde or ketone groups, including Schiff base formation, nucleophilic addition, and reductive amination. The obtained polysaccharide aldehydes or ketones themselves have rich potential for making useful materials, such as self-healing hydrogels, polysaccharide–protein therapeutic conjugates, or drug delivery vehicles. Herein, we review recent advances in synthesizing polysaccharides containing aldehyde or ketone moieties and briefly introduce their reactivity and corresponding applications.
Biopolymer-based materials for the adsorption of toxic dyes represent an interesting class of materials for environmental applications. Here we report on chitosan as the starting material for synthesizing dye adsorbents. In particular, the synthesis, characterization, and cationic dye adsorption properties of chitosan hydrogel adsorbents are reported. Polyanionic itaconated chitosan derivatives were synthesized in solvent-less conditions for the first time. Itaconated chitosan was cross-linked using thiol-ene chemistry to obtain hydrogels. The influence of the incorporated carboxylate groups and the cross-linker fraction on the adsorption of Methylene Blue (MB) was investigated. In addition, the impact of pH, adsorbent dose, initial concentration, and ionic strength were investigated to determine the optimum conditions for MB uptake, and the dye uptake kinetics, adsorption isotherms, selectivity, and reusability of the adsorbents were unveiled. A maximum adsorption capacity of 556 mg/g could be achieved, outperforming commercial activated charcoal and ion exchange resins. Furthermore the chitosan hydrogel adsorbents were shown to capture >90 % of cationic MB from a binary equimolar mixture with the anionic dye Methyl Orange. Since the adsorbents can be regenerated and re-used afterwards at least 20 times, retaining a high dye adsorption fraction of >95 %, these materials are promising candidates for environmental applications.
This study aims to design an anionic, thiolated cellulose derivative and to evaluate its mucoadhesive and permeation-enhancing properties utilizing enoxaparin as a model drug. 2-Mercaptosuccinic acid-modified cellulose (cellulose–mercaptosuccinate) was synthesized by the reaction of cellulose with S-acetylmercaptosuccinic anhydride. The chemical structure of the target compound was confirmed by FTIR and ¹H NMR spectroscopy. The thiol content was determined by Ellman’s test. The conjugate exhibited 215.5 ± 25 μmol/g of thiol groups and 84 ± 16 μmol/g of disulfide bonds. Because of thiolation, mucoadhesion on porcine intestinal mucosa was 9.6-fold enhanced. The apparent permeability (Papp) of the model dye Lucifer yellow was up to 2.2-fold improved by 0.5% cellulose–mercaptosuccinate on a Caco-2 cell monolayer. Enoxaparin permeation through rat intestinal mucosa increased 2.4-fold in the presence of 0.5% cellulose–mercaptosuccinate compared with the drug in buffer only. In vivo studies in rats showed an oral bioavailability of 8.98% using cellulose–mercaptosuccinate, which was 12.5-fold higher than that of the aqueous solution of the drug. Results of this study show that the modification of cellulose with 2-mercaptosuccinic acid provides mucoadhesive and permeation-enhancing properties, making this thiolated polymer an attractive excipient for oral drug delivery.
Nature-derived or biologically encouraged hydrogels have attracted considerable interest in numerous biomedical applications owing to their multidimensional utility and effectiveness. The internal architect of a hydrogel network, the chemistry of the raw materials involved, interaction across the interface of counter ions, and the ability to mimic the extracellular matrix (ECM) govern the clinical efficacy of the designed hydrogels. This review focuses on the mechanistic viewpoint of different biologically driven/inspired biomacromolecules that encourages the architectural development of hydrogel networks. In addition, the advantage of hydrogels by mimicking the ECM and the significance of the raw material selection as an indicator of bioinertness is deeply elaborated in the review. Furthermore, the article reviews and describes the application of polysaccharides, proteins, and synthetic polymer-based multimodal hydrogels inspired by or derived from nature in different biomedical areas. The review discusses the challenges and opportunities in biomaterials along with future prospects in terms of their applications in biodevices or functional components for human health issues. This review provides information on the strategy and inspiration from nature that can be used to develop a link between multimodal hydrogels as the main frame and its utility in biomedical applications as the primary target.
Environmental issues related to the use of plastic packaging have sparked a growing interest in the development of more sustainable solutions. Biopolymers, used alone or in combina-tion with other materials, have been considered a potential alternative to conventional fos-sil-based plastics. Hence, this study aimed at unraveling the potentiality offered by polysac-charides for food packaging applications. To that purpose, an extended characterization of the barrier (to oxygen and water vapor), mechanical and optical properties (transparency and UV-blocking ability) of nine different polysaccharide films (hydroxypropyl methyl-cellulose, methylcellulose, hydroxypropyl cellulose, low-methoxyl pectin, cationic starch, sodium alginate, kappa-carrageenan, chitosan, and pullulan) was performed to provide a broad overview of their main physicochemical properties under standardized conditions. In addition, the properties of the film-forming solutions, such as viscosity and surface tension, were also evaluated. All polysaccharides obviously presented low water vapor barrier per-formance due to their hydrophilic nature (water vapor permeance from 10−6 to 10−8 mol.m−2.s−1.Pa−1). Among all the polysaccharides studied, chitosan, low-methoxyl pectic, kappa-carrageenan, pullulan, cationic starch and sodium alginate, displayed medium to very high oxygen barrier performance in semi-dry (50 % RH) and humid (80 % RH) conditions (oxygen permeance from 10-14 to 10-15 mol.m−2.s−1.Pa−1), contrarily to cellulose derivatives which showed the poorest performance (oxygen permeance > 10−12 mol.m−2.s−1.Pa−1). This opens on interesting perspectives for the use of polysaccharides as coating materials for high oxygen barrier packaging.
A polysaccharide obtained from maca (Lepidium meyenii) root extract (MREP) was evaluated as a novel, inexpensive, biocompatible corrosion inhibitor for mild steel (MS) in 1 M HCl. Fourier transform infrared (FTIR) and nuclear magnetic resonance studies were conducted to characterize the inhibitor. Gravimetric, electrochemical impedance spectroscopy (EIS), and potentiodynamic polarization (PDP) techniques were applied to assess the corrosion inhibition potential of the inhibitor. Gravimetric studies were conducted over the temperature range of 30–60 °C. The inhibition efficiency of MREP increased with the concentration and temperature. The maximum inhibition efficiency of MREP was 94.78% at 700 ppm and 60 °C. EIS analysis showed that as the MREP concentration increased, the Rp value obtained from the Nyquist plot increased due to the formation of MREP barrier film at the MS/solution interface. PDP analysis showed that MREP had a mixed type inhibition mechanism. The inhibition efficiencies calculated based on gravimetric, EIS, and PDP analyses were similar. Ultraviolet–visible, FTIR, X-ray photoelectron spectroscopy, atomic force microscopy, and scanning electron microscopy/energy dispersive X-ray spectroscopy (SEM/EDAX) analyses demonstrated the formation of a protective film on the MS surface. MREP adsorbed on MS according to the Langmuir adsorption isotherm. The calculated density functional theory parameters indicated the formation of a strong bond between MREP and the unoccupied d-orbital of iron atoms in MS. By contrast, Monte Carlo simulations indicated the adsorption of the MREP inhibitor on the MS surface at the atomic level.
Here, we introduce κ-carrageenan and sodium alginate based hydrogel (CAG-NaAlg-cl-polyAA) and hydrogel nanocomposite (CAG-NaAlg-cl-polyAA/Fe3O4) through a free radical crosslinking method using acrylic acid/ N,N’- methylenebisacrylamide as a monomer/crosslinker system. The hydrogel is stimuli-responsive and its water absorption efficiency is enhanced through the optimization of synthesis parameters. The synthesized superabsorbents have been sequentially characterized through HR-TEM, powder XRD, FTIR, SEM-EDS, and XPS analysis. The average particle size of Fe3O4 nanoparticles stabilized through the CAG-NaAlg-cl-polyAA hydrogel matrix is 10.7 ± 2.5 nm. The CAG-NaAlg-cl-polyAA hydrogel exhibited > 95% dye removal efficiency for the removal of basic dyes (auramine O, crystal violet and malachite green), whereas the % dye removal potential of CAG-NaAlg-cl-polyAA/Fe3O4 is enhanced upto 99% after the incorporation of Fe3O4 nanoparticles. Langmuir adsorption is the most favorable adsorption isotherm with R² = 0.992 (auramine O, AU), 0.989 (malachite green, MG), and 0.974 (crystal violet, CV). Kinetic studies indicate that the adsorption of AU, CV, and MG follows pseudo 2nd order kinetics. Moreover, the reusability of the fabricated samples upto five consecutive cycles further explores its potential for the separation of basic textile dyes from industrial wastewater.
Poly-anionic Xanthan gum-based hydrogels were synthesized and used as potent adsorbents for the removal of dye pollutants from waste water effluents. The adsorbents were synthesized by esterification of Xanthan gum with maleic anhydride, followed by thiol-ene cross-linking chemistry with 2,2′-(ethylenedioxy)diethanethiol. Methylene blue was used as model cationic dye to mimic dye polluted water. The adsorption kinetics of methylene blue by the Xanthan gum-based hydrogels was modeled by pseudo-first-order, pseudo-second-order and intraparticle diffusion models. The experimental adsorption data at 25°C was modeled by the Langmuir isotherm. The effects of adsorption operation parameters such as the initial dye concentration, pH, ionic strength, and adsorbent dose were also investigated. The pseudo-second-order and Langmuir models were found to be the most appropriate models for the description of the adsorption kinetics and isotherm data, respectively. The Xanthan gum-based hydrogel exhibited a high adsorption capacity of up to qmax=435 mg/g (1.35 mmol/g) towards methylene blue. The incorporation of carboxylic acid groups in the Xanthan gum backbone afforded appreciable charge density at pH > 5, which can effectively facilitate the binding of cationic dye molecules. Consequently, the uptake mechanism of methylene blue by the polyanionic Xanthan hydrogel is attributed mainly to the electrostatic interactions. The Xanthan gum-based hydrogel had a remarkable selectivity for the cationic dye in binary and ternary mixtures of methylene blue with methyl orange or sunset yellow FCF. Finally, the hydrogel showed a potential to be re-used for at least for twenty times after regeneration and maintaining over 95% efficiency dye removal as well as recovery.
Carbon nanotubes (CNTs) were added into the self-healing polyurethane materials as conductive filler, the mass fraction of carbon nanotubes was adjusted, and 1% polyaniline was doped. The conductive self-healing polyurethane composites with different carbon nanotubes content (PU)-1/3/5/8/10 were prepared, and analyzed and tested. The result shows that the permeability threshold value of the composite material is 8wt%, and the comprehensive performance of the composite material PU-8 is the best; the resistance of PU-8 is 1278Ω, PU-8P has a resistance of 1400Ω; using an infrared camera, it can be seen that the material can reach 143.3 °C under the DC current of 0.1A, reaching the temperature condition when the material is repaired; the swelling test shows that the PU-8P equilibrium swelling rate is 177%, the gel content is 52.67%, and there is no dissolution in dimethyl sulfoxide. Solvent stability is better than PU-8;DSC test shows that the glass transition temperature of the soft segment of PU-8P is 43 °C, and the glass transition temperature of the hard segment is − 55 °C, which is not much different from that of PU-8; TG test shows that the epitaxial starting temperature of PU-8P is 365 °C; the observation photo is magnified by a stereo microscope at ten times and the PU-8P sample is cut of in the middle at room temperature, applying a constant voltage of 30 V, the cracks disappeared. The material cracks realized self-healing with electricity, and the repair efficiency reached 20.5%.
The fabrication of covalently cross-linked high-surface-area biopolymeric nanogel fibers by nanopore extrusion is reported for the first time. The biopolymer pullulan was functionalized with tert-butyl acetoacetate via a transesterification reaction to synthesize the water-soluble ketone-rich precursor pullulan acetoacetate (PUAA). PUAA and carbonic dihydrazide (CDH) as cross-linker were extruded through anodic aluminum oxide (AAO) nanoporous membranes, which possessed an average pore diameter of 61 ± 2 nm. By changing the concentration of PUAA, the flow rate, and extrusion time, the step polymerization cross-linking reaction was controlled so that the polymer can be extruded gradually during cross-linking through the membrane, avoiding the formation of macroscopic bulk hydrogels and rupture of the AAO membrane. Fibers with diameters on the order of 250 nm were obtained. This approach was also expanded to functionalized PUAA derivatives together with the fluorogenic substrate 4-methylumbelliferyl-β-d-glucuronide MUGlcU in (PUAA-MUGlcU), which exhibited a mean equilibrium swelling ratio of 5.7 and 9.0 in Milli-Q water and in phosphate-buffered saline, respectively. β-Glucuronidase was sensitively detected via fluorescence of 4-methylumbelliferone, which was liberated in the enzymatic hydrolysis reaction of PUAA-MUGlcU. Compared to hydrogel slabs, the rate of the hydrolysis was >20% higher in the nanogel fibers, facilitating the rapid detection of β-glucuronidase-producing Escherichia coli (E. coli Mach1-T1). Nanopore extruded nanogel fibers are therefore considered a viable approach to enhance the functionality of hydrogels in surface-dominated processes.
Polymer brush synthesis is a powerful approach to fabricate functional bio-interfaces. To enhance the control over brush synthesis and end groups, we have synthesized poly(glycidyl methacrylate) PGMA brushes with carboxylic acid end functional groups by interface-mediated dissociative electron transfer reversible addition-fragmentation chain transfer radical (DET-RAFT) polymerization on titanium surfaces. This method does not require the use of metals and occurs under mild conditions. The brushes obtained were analyzed comprehensively in order to understand how to control cell attachment behavior. The PGMA brushes synthesized by DET-RAFT polymerization were characterized by X-ray photoelectron spectroscopy (XPS), grazing angle Fourier transform infrared (GA-FTIR) spectroscopy, water contact angle measurements and variable angle spectroscopic ellipsometry. The terminal carboxylic acid functional groups were covalently conjugated with arginine-glycine-aspartic acid (RGD) and arginine-alanine-aspartic acid (RAD, negative control) peptides in one step. RGD selective attachment of NIH3T3 fibroblasts was observed exclusively on PGMA-RGD brushes. Thus, a new versatile strategy has been validated to obtain functional biointerfaces for selective cell attachment in the absence of any metallic catalyst.
Oxidation of polysaccharides has been a useful approach to new materials. However, selectivity in oxidation of polysaccharide macromolecular polyols remains a significant challenge with few methods for the synthesis of ketone-substituted polysaccharides. We report here a selective, practical, and efficient process, beginning with 2-hydroxypropyl ethers of polysaccharides that are simple and economical to prepare. We demonstrate this approach herein using commercial 2-hydroxypropyl cellulose (HPC) and 2-hydroxypropyl dextran (HPD) that we prepared. We oxidize the terminal, secondary alcohols of the oligo(2-hydroxypropyl) substituents with sodium hypochlorite so that the product has an oligo(2-hydroxypropyl) side chains terminated by a ketone. We demonstrate the high chemo- and regioselectivity of this oxidation by analytical methods including hydrolysis to monosaccharides and mass spectrometry of the resulting mixture. We provide an initial demonstration of the potential utility of these keto-polysaccharides by reacting Ox-HPC with primary amines to form Schiff base imines, providing proactive polymers.
The effect of systematically varied mechanical properties and nano- and microscale surface topography on the adhesion and proliferation of human pancreatic cancer cells on fibronectin-functionalized poly(vinyl alcohol) (PVA) hydrogels was studied in order to understand the impact of these properties of the cell microenvironment on cell attachment and spreading. The mechanical properties of PVA, as assessed by atomic force microscopy (AFM) nanoindentation, were varied by the number of freezing-thawing cycles in the physical cross-linking process used for the generation of the hydrogels. Nano- and micropatterned hydrogel surfaces exposing nanosized PVA pillars and cuboids were fabricated by replicating ordered cylindrical nanopores of anodic aluminum oxide (AAO) and polydimethylsiloxane (PDMS) templates, respectively. Softer PVA hydrogels, functionalized covalently with fibronectin, showed enhanced cell adhesion and proliferation of PaTu 8988t cells in comparison to stiffer hydrogels. In addition, PaTu 8988t cells favored the nanopatterned surfaces over micropatterned and flat hydrogels.
Here, we report the striking properties such as high stretchability, self-healing, and adhesiveness of an amphiphilic copolymeric hydrogel (PAA-PMMA gel) synthesized from two immiscible monomers—acrylic acid (AA) and methyl methacrylate (MMA)—through a simple free radical polymerization in an aqueous medium. The developed hydrogel with a specific molar ratio of MMA and AA, is self-healable, which is attributed to the hydrophobic interaction arises from methyl groups of PMMA, as well as the breakdown and reformation of sacrificial noncovalent crosslinking through the weak hydrogen bonds between the carboxylic acid groups of PAA and methoxy groups of PMMA. The energy dissipation values in the hysteresis test signify the excellent self-recoverability of the hydrogel. The developed hydrogel showed adhesive behavior to the surfaces of polystyrene, glass, wood, metal, stone, ceramics, pork skin and human skin. The physical and mechanical properties of the PAA-PMMA gel were fine-tuned through changes in the MMA/AA ratio and pH. Moreover, the PAA-PMMA hydrogel can serve as a template for calcium phosphate mineralization to yield a hydrogel composite which improved MC3T3 cell adhesion and proliferation. Overall, we propose that depending on synthesis parameters and other scenarios, the synthesized PAA-PMMA hydrogel could potentially be employed in varying biomedical and industrial applications.
In the present work, cellulose acetoacetates (CAA) was used as a precursor for preparing diversely functionalized cellulose derivatives. Four amino-bearing compounds, namely hexylamine (HA), L-glutamic acid (Glu), cysteine (Cys), and tyramine (TA) were reacted with acetoacetyl groups providing alkyl-, carboxyl-, thiol-, or phenolic functionalized cellulose. The reaction was conducted under mild conditions without catalysts and UV light. The products were characterized with FT-IR, NMR and solubility measurement. ¹H NMR measurement demonstrated the conversion of acetoacetyl groups were ideal, and all the cellulose derivatives demonstrated good solubility in certain solvent. Besides, CAA held a good stability under room temperature. This approach offers broad possibilities for developing new cellulose based materials. Moreover, this protocol can also be applied to fabricate other polysaccharide derivatives.
Improving the wettability of and reducing the protein adsorption to contact lenses may be beneficial for improving wearer comfort. Herein, we describe a simple “click” chemistry approach to surface functionalize poly(2-hydroxyethyl methacrylate) (pHEMA)-based contact lenses with hyaluronic acid (HA), a carbohydrate naturally contributing to the wettability of the native tear film. A two-step preparation technique consisting of laccase/TEMPO-mediated oxidation followed by covalent grafting of hydrazide-functionalized HA via simple immersion resulted in a model lens surface that is significantly more wettable, more water-retentive, and less protein binding than unmodified pHEMA while maintaining the favorable transparency, refractive, and mechanical properties of a native lens. The dipping/coating method we developed to covalently tether the HA wetting agent is simple, readily scalable, and a highly efficient route for contact lens modification.
A self-healing polysaccharide hydrogel based on dynamic covalent enamine bonds has been prepared with a facile, cost-effective, and eco-friendly way. The polysaccharide hydrogel is obtained by mixing cellulose acetoacetate (CAA) aqueous solution with chitosan aqueous solution under room temperature. CAA is synthesized by reaction of cellulose with tert-butyl acetoacetate (t-BAA) in ionic liquid 1-allyl-3-methylimidazolium chloride (AMIMCl). The structure and properties of CAA are characterized by FT-IR, NMR, and solubility measurements. The results demonstrate that CAA possesses water solubility with a degree of substitution (DS) about 0.58-1.11. The hydrogel shows an excellent self-healing behavior without other external stimuli and good stability under physiological conditions. Furthermore, the polysaccharide hydrogel exhibits pH responsive properties.