Mechanism For Hydrogel Formation Research Articles

3D printed arrowroot starch-gellan scaffolds for wound healing applications

Skin, the largest organ in the body, blocks the entry of environmental pollutants into the system. Any injury to this organ allows infections and other harmful substances into the body. 3D bioprinting, a state-of-the-art technique, is suitable for fabricating cell culture scaffolds to heal chronic wounds rapidly. This study uses starch extracted from Maranta arundinacea (Arrowroot plant) (AS) and gellan gum (GG) to develop a bioink for 3D printing a scaffold capable of hosting animal cells. Field emission scanning electron microscopy (FE-SEM) and X-ray diffraction analysis (XRD) prove that the isolated AS is analogous to commercial starch. The cell culture scaffolds developed are superior to the existing monolayer culture. Infrared microscopy shows the AS-GG interaction and elucidates the mechanism of hydrogel formation. The physicochemical properties of the 3D-printed scaffold are analyzed to check the cell adhesion and growth; SEM images have confirmed that the AS-GG printed scaffold can support cell growth and proliferation, and the MTT assay shows good cell viability. Cell behavioral and migration studies reveal that cells are healthy. Since the scaffold is biocompatible, it can be 3D printed to any shape and structure and will biodegrade in the requisite time.

Chlorella protein hydrogel preparation and its application in loading and slow release of poly(lysine)

This article is dedicated to the preparation of a novel Chlorella protein hydrogel that can be used as a slow release carrier. Chlorella proteins and alginate were used as cross-linking agent at the present of 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide/N-hydroxysuccinimide to obtain hydrogel with different 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide/N-hydroxysuccinimide concentration. Textural results showed that hydrogel with high N-hydroxysuccinimide concentration possessed good hardness, springiness, gumminess and chewiness, espasically those hydrogel with 23% N-hydroxysuccinimide concentration. Scanning electron microscopy results revealed that the prepared hydrogel with higher N-hydroxysuccinimide concentration had better stable spatial porous structures. Swelling analyses indicated the prepared hydrogel exhibited pH sensitivity, which were beneficial for the slow-release. Then the hydrogels with 23% N-hydroxysuccinimide were used to be poly(lysine) slow-release carriers. Moreover, this hydrogel exhibited a prolonged and efficient period of poly(lysine) slow release at pH 1.2 (30%) and 7.4 (95%) within 200 h, which were further proved by good antibacterial activity against Escherichia coli and Staphylococcus aureus. Finally, based on the above results, we simulated the mechanism of hydrogel formation and poly(lysine) loading and slow release. The results reveal that the prepared Chlorella protein hydrogels are beneficial for use as slow-release carriers.

Highly gallol-substituted, rapidly self-crosslinkable, and robust chitosan hydrogel for 3D bioprinting

Although three-dimensional (3D) bioprinting is a promising technology for reconstructing artificial tissues and organs using bioink, there is a lack of a bioink that satisfies all requirements, including printability, gelation, mechanical properties, and cytocompatibility, Herein, a novel self-crosslinkable bioink derived from chitosan (CS) and gallic acid (GA) is presented. 3D printed scaffolds with excellent shape fidelity are realized by systematically analyzing the self-crosslinking mechanism of hydrogel formation from CS-GA conjugates and by optimizing various parameters of the printing process. The CS-GA hydrogel forms rapidly in a physiological pH without any chemical crosslinking agent. In addition, the CS-GA hydrogel exhibited various physical and chemical intermolecular interactions, fast gelation rates, and excellent mechanical properties (>337 kPa). Moreover, the CS-GA hydrogel singificantly improves the cell viability (>92 %) and proliferation of the bioink. Therefore, the self-crosslinkable CS-GA bioink has great potential to overcome the limitations of conventional bioinks.

Preparation and characterization of smart therapeutic pH-sensitive wound dressing from red cabbage extract and chitosan hydrogel

Developing a multifunctional wound dressing that protects, cures and indicates the healing progress, is a new approach of investigation. Red cabbage extract (RCE), consisting of bioactive compounds that have antioxidant, anti-inflammatory, anti-carcinogenic, bactericidal, antifungal, and antiviral activities, was utilized as a natural pH-sensitive indicator. Chitosan-based hydrogel, encapsulating RCE, was developed to obtain a smart therapeutic pH-sensitive wound dressing as antimicrobial bio-matrix provides a comfortable cushion for wound bed and indicates its status. Methacrylated-chitosan was crosslinked by different concentrations of methylenebisacrylamide (MBAA) by which hydrogel mechanical and morphological properties were tuned. The proposed mechanism for hydrogel formation was confirmed by FT-IR. The coloristic properties of the RCE and the changes in color intensity as a function of pH were confirmed by UV–Vis spectroscopy. The effect of MBAA on the mechanical, swelling, release and morphological properties of hydrogel were investigated. MBAA (2.5% wt/v) in 2% wt/v chitosan showed preferable mechanical (20 KPa), swelling (1294% at pH 8 ± 0.2), and release (prolonged up to 5 days) properties. Hydrogel matrices, loaded on cotton gauze submerged in different pH buffer solutions, showed explicit color changes from green to red as pH changed from 9 to 4.

Nanosheets and Hydrogels Formed by 2 nm Metal-Organic Cages with Electrostatic Interaction.

We report the mechanism of hydrogel formation in dilute aqueous solutions (>15 mg/mL) by 2 nm metal-organic cages (MOCs). Experiments and all-atom simulations confirm that with the addition of small electrolytes, the MOCs self-assemble into 2D nanosheets via counterion-mediated attraction because of their unique molecular structure and charge distribution as well as σ-π interactions. The stiff nanosheets are difficult to bend into 3-D hollow, spherical blackberry type structures, as observed in many other macroion systems. Instead, they stay in solution and their very large excluded volumes lead to gelation at low (∼1.5 wt %) MOC concentrations, with additional help from hydrophobic and partial π-π interactions similar to the gelation of graphene oxides.

Hydrogels for cancer drug delivery

Developing the assurance and potency proportion of actual chemotherapeutic medicament is an ongoing task that needs to be worked upon hand in hand with development of new chemotherapeutics agents that require a great deal of time and cost. Hydrogels have emerged as promising drug delivery systems which can efficiently provide both contiguous and sensual control over the discharge of numerous therapeutics. They have also found use in contact lens manufacture, cosmetics, hygienic products, wound healing. In addition to facilitating building up organoids and organ on a chip of hydrogels have thus become an important issue as drug delivery systems for chemotherapeutics. This review emphasis on the mechanisms of hydrogels, mechanism of hydrogel formation, their types and applications of various hydrogels as a delivery system for chemotherapeutic agent. Studies had made tremendous advances in reconstruction of the tumor form, tumor treatment and related therapies due to the special properties of hydrogels. Notably, it is possible to adjust hydrogel-based devices to react to internal stimuli specific to cancer. Such well-known medicament storage is adopted as intelligent transports for various cargoes, namely chemotherapeutics, genes, and radioisotopes, both bare and nanoparticle-encapsulated. Hydrogels can provide spatial and temporal influence over the discharge of several biomedical products, along with medicines for small molecules, macromolecular drugs and cells.

A novel folic acid hydrogel loading β-cyclodextrin/camptothecin inclusion complex with effective antitumor activity

Folic acid, as a significant vitamin, is essential for human bodies, especially for pregnant women. However, folic acid hydrogel for drug delivery has not been reported until now. Herein, folic acid hydrogel was prepared by ion inducing method firstly. Then β-cyclodextrin/camptothecin inclusion complex was loaded into folic acid hydrogel successfully by co-assembly. Camptothecin loading folic acid hydrogel has good rheological mechanical property and thermodynamic stability. Moreover, the possible mechanism of hydrogel formation was proposed by energy dispersive spectrometer and small-angle X-ray scattering. Besides, compared to camptothecin itself, camptothecin release rate from camptothecin loaded hydrogel was prolongated remarkably through dialysis experiment. Finally, the cell inhibitory rate of camptothecin loading folic acid hydrogel was increased observably compared to camptothecin itself. Hence, as a green drug delivery system, our folic acid hydrogel has important potential application in medical engineering material. Herein, a novel β-cyclodextrin/camptothecin inclusion complex loaded folic acid hydrogel was constructed by elaborate design and preparation, which can load camptothecin into folic acid hydrogel effectively. Moreover, compared to camptothecin itself, camptothecin release rate from camptothecin loaded hydrogel was prolongated remarkably through dialysis experiment. Finally, the cell inhibitory rate of camptothecin loading folic acid hydrogel was increased observably compared to camptothecin itself. Hence, as a green drug delivery system, our folic acid hydrogel has important potential application in medical engineering material.

Montmorillonite Nanocomposite Hydrogel Based on Poly(acrylicacid-co-acrylamide): Polymer Carrier for Controlled Release Systems

In this paper, the synthesis of new montmorillonite nanocomposite hydrogel (MMTNH) based on poly (acrylic acid-co-acrylamide) grafted onto starch, is described. Montmorillonite (MMT) as nanometer base, acrylic acid (AA) and acrylamide (AAm) as monomers, ammonium persulfate (APS) as an initiator, N,N-methylenebisacrylamide (MBA) as a crosslinker and starch as a biocompatible polymer were prepared in aqueous solution and their amounts were optimized to attain the highest water absorbance. The optimized swelling capacity in distilled water was found to be 810 g/g. A mechanism for hydrogel formation was proposed and the structure of the product was confirmed using a set of techniques including FT-IR spectroscopy, thermogravimetric analysis, scanning electron microscopy, transmission electron microscopy, atomic force microscopy, and X-ray powder diffraction. Furthermore, the swelling behaviors of the nanocomposite at different pHs, various salt with different concentrations, the mixture of solvents, were investigated. The methylene blue (MB) dye was used as model drugs to assess the loading and release by MMTNH. The pH response of this MMTNH makes it suitable for acting as a controlled delivery system. The results suggest MMTNH may find applications as promising drug delivery vehicles for drug molecules.

An injectable and self‐healing novel chitosan hydrogel with low adamantane substitution degree

AbstractChitosan (CS) is a semi‐natural polymer with supreme biological function, while the strong interchain hydrogen bonds cause poor water solubility and limit its broader use. To break the semi‐rigid structure of CS, a kind of CS modified by adamantane (AD‐CS) was successfully synthesized by amidation reaction with 1‐(3‐dimethylaminopropyl)‐3‐ethylcarbodiimide hydrochloride as catalyst. The chemical structure of AD‐CS was characterized by Fourier transform infrared spectroscopy and 1H NMR. The AD substitution degree of CS is around 2%, calculated by 1H NMR. A soft and transparent hydrogel composed of hydrogen bonds was obtained directly by simply adding a certain amount of water under mild conditions. Rheological measurements were carried out to research the mechanism of hydrogel formation by measuring the influence of different additives and conditions on the AD‐CS hydrogel. Reinforced hydrogels were prepared by freezing and thawing. The mechanical strength and self‐healing property of reinforced and pristine hydrogels were assessed with an oscillatory rheometer. The modulus of the reinforced hydrogel was obviously enhanced without much loss of self‐healing property. Other properties such as adhesion, injectability and temperature response were also studied. These injectable and self‐healing hydrogels show potential value in medical care. Additionally, this is a new method to design CS hydrogels with their original interchain hydrogen bonds. © 2019 Society of Chemical Industry

The Formation Mechanism of Hydrogels.

Hydrogels are degradable polymeric networks, in which cross-links play a vital role in structure formation and degradation. Cross-linking is a stabilization process in polymer chemistry that leads to the multi-dimensional extension of polymeric chains, resulting in network structures. By crosslinking, hydrogels are formed into stable structures that differ from their raw materials. Generally, hydrogels can be prepared from either synthetic or natural polymers. Based on the types of cross-link junctions, hydrogels can be categorized into two groups: the chemically cross-linked and the physically cross-linked. Chemically cross-linked gels have permanent junctions, in which covalent bonds are present between different polymer chains, thus leading to excellent mechanical strength. Although chemical cross-linking is a highly resourceful method for the formation of hydrogels, the cross-linkers used in hydrogel preparation should be extracted from the hydrogels before use, due to their reported toxicity, while, in physically cross-linked gels, dissolution is prevented by physical interactions, such as ionic interactions, hydrogen bonds or hydrophobic interactions. Physically cross-linked methods for the preparation of hydrogels are the alternative solution for cross-linker toxicity. Both methods will be discussed in this review.

Synthesis and morphological insight of new biocompatible smart hydrogels

We present a first report for developing stimulus responsive hydrogels via free radical aqueous polymerization technique using Acrylic acid (AAc), methacrylic acid (MAAc) and diethylaminoethyl methacrylate (DEAEMA). The morphological aspects of poly(AAc-co-DEAEMA) (pAcD) and poly(MAAc-co-DEAEMA) (pMcD) were investigated to delineate the relevant mechanism of hydrogel formation for better understanding of their mechanical behaviour. The formulated hydrogels were found to have a structural framework comprising inter-connected nanogels and continuous outer skin with macroporous interiors. An abrupt increase in the peak intensities specific to the polymer and a simultaneous decrease in the water related peaks in the attenuated total reflectance Fourier transform infrared (ATR-FTIR) spectra exhibited the phenomenon of phase separation, whereas peaks of proton nuclear magnetic resonance (1HNMR) revealed hydrogen bonding and electrolytic complexation between the monomers. Biocompatibility is the hallmark for any drug carrier and was evaluated by both in vitro and in vivo testing. Administration of the prepared hydrogels to rat models did not cause any significant affect on the vital organs.

Preparation and characterization of chitosan-based hydrogel for drug delivery of 5-Fluro uracile

In this paper, we reported the synthesis and behavior of chitosan based hydrogel and controlled drug delivery by hydrogel in different pH. The chitosan based hydrogel was synthesized via bonding of acetaldehyde monomer on chitosan .the mechanism of hydrogel formation confirmed by FT-IR, SEM, and XRD. The hydrogel absorbtion rate was studied in pH 1-12. Loading of 5-Fluro uracile drug, loaded rate and drug delivery percent have been done in buffer solutions of pH 1 to 12.

A novel chitosan-collagen-based hydrogel for use as a dermal filler: initial in vitro and in vivo investigations.

Novel hydrogels (termed HCD hydrogels) were synthesized based on human-like collagen (HLC) and chitosan (CS) cross-linked with dialdehyde starch (DAS). The biological stability and biocompatibility of HCD hydrogels were determined through in vitro and in vivo tests. The mechanism of hydrogel formation was studied using Fourier transform infrared spectroscopy (FTIR), which showed that covalent bonds formed via acetalization and Schiff base reactions. Biological stability was evaluated in vitro by degrading HCD hydrogels with class I collagenase, class II collagenase, and both class I and class II collagenases and in vivo after subcutaneously injecting HCD into an animal model. The biological characteristics of HCD hydrogels was studied by two methods: (i) MTT and cytomorphology cytotoxicity and cytocompatibility and (ii) in vivo, whereby histomorphometry, transmission electron microscopy (TEM), and immunohistochemistry were used to compare different types of surgically introduced hydrogels, our HCD hydrogels, SunMax Collagen Implant hydrogels (SUM hydrogels), and OUTLINE&EVOLUTION Injectable Synthetic Gel hydrogels (EVL hydrogels). The in vivo analyses were performed at 1, 9, 12, and 28 weeks after surgery. The hydrogel biodegradation results showed that the normalized residual weight (WR) of HCD hydrogels varied with DAS content. In vitro, we found that the minimum WR of HCD hydrogels was 42.19% after 28 weeks when degraded by both types of class I and class II collagenase. The MTT assay indicated that the minimum relative growth rate (RGR) of cells was 93% after they were incubated with HCD hydrogels for 7 days, suggesting good cytocompatibility. In vivo histomorphometry results indicated that HCD hydrogels effectively filled tissue voids and did not cause redness, edema, festering, or color changes. In addition, a few vessels grew into the hydrogel and a thin fibrous capsule was eventually produced. TEM and immunohistochemistry studies suggested that HCD hydrogels produced less intense inflammatory responses than those produced by SUM hydrogels and EVL hydrogels. Overall, HCD hydrogels afford both enhanced biological stability and excellent biocompatibility, making them potentially promising for skin patch scaffolds, wrinkle treatments, and tissue cavity fillers.

Cross‐link copolymerization of cationic starch by gamma irradiation and its swelling‐shrinking and flocculating behaviors

AbstractCationic starch‐based hydrogels were synthesized by simultaneously irradiating starch, acrylamide (AM), dimethyldiallylammonium chloride (DMDAAC), and N,N′‐methylenebisacrylamide (MBA) in aqueous solution. A mechanism for hydrogel formation was proposed, and the product was characterized by NMR spectroscopy. Results showed that a minimum amount of AM and a maximum amount of DMDAAC were grafted onto the starch backbone at an absorbed dose of 4 kGy and a starch/AM/DMDAAC weight ratio of 6:9.8:4.2, while NDMDAAC/NAM reached its maximum value of 0.17. The equilibrium swelling ratio (Se) of the hydrogels progressively decreased with increased absorbed dose at a fixed starch/AM/DMDAAC/MBA ratio of 6:9.8:4.2:1.6, but the swelling rate parameter (τ) initially decreased up to 3 kGy and then increased. Meanwhile, the hydrogels showed similar shrinking behaviors with increased absorbed dose. At a fixed starch/AM/DMDAAC weight ratio of 6:9.8:4.2 and fixed gamma irradiation of 3 kGy, Se and τ decreased with increased MBA and solvent volume, but both water‐loss rate (Rloss) and minimum mass maintenance ratio (Rm0) progressively increased at 60°C. At a constant starch:AM:DMDAAC:MBA wt. ratio of 6:9.8:4.2:1.6, the flocculating activity of SADM decreased with absorbed dose increasing. The optimal flocculant concentration was 4 mg/L for SADMs synthesized at 1 and 2 kGy.

Multiple-stimulus-responsive hydrogels of cationic surfactants and azoic salt mixtures

New hydrogels having high water content, ∼96 wt%, composed of cationic surfactants, alkyltrimethylammonium bromides (C n TAB, n = 12, 14, 16, and 18), and a small dye molecule, sodium azobzenzene 4,4′-dicarboxylic acid (AzoNa2), was firstly obtained. The three-dimensional network structures of hydrogels were determined by transmission electron microscopy images, scanning electron microscopy images, 1H nuclear magnetic resonance, and small-angle X-ray scattering measurements. The mechanism of hydrogel formation was also illustrated. The rheological data were obtained to investigate the mechanical strength of hydrogels, which were turned out to be strong mechanical strength (∼104 Pa) materials. We found that the strength of the hydrogel depends on the fiber density, which can be controlled by changing the proportion of the two compounds, concentration of surfactants, temperature, and the chain length of the surfactant. Interestingly, the hydrogels were found to have a multiple-stimulus response property. A reversible thermal, UV–vis, or a chemical response was investigated in the mixtures of cationic surfactants and azoic salt for the first time. These findings may find potential applications such as sensors, actuators, shape memories, and drug delivery systems, etc.

Synthesis and Investigation of a Novel pH- and Salt-Responsive Superabsorbent Hydrogel Based on Pectin

In the present paper, attention is paid to synthesis and investigates swelling behavior of a superabsorbent hydrogel based on Pectin (Pec) and polyacrylic acid (PAcA). acrylic acid (AcA) was graft copolymerized onto Pectin backbones by a free radical polymerization technique using ammonium persulfate (APS) as initiator and methylene bisacrylamide (MBA) as a crosslinker. A proposed mechanism for hydrogel formation was suggested and the structure of the product was established using FTIR and SEM spectroscopies. Under the optimized conditions concluded, maximum capacity of swelling in distilled water was found to be 348 g/g. Absorbency of the synthesized hydrogels was also measured in NaCl and CaCl 2 salt solutions. Results indicated that the swelling ratios in compare to water decreased with an increase in the ionic strength of solution. In addition, swelling capacity was conducted in solutions with pH ranged from 1 to 13. The H-Pec- poly(sodium acrylate) hydrogel exhibited a pH-responsiveness character so that a swelling- deswelling pulsatile behavior was recorded at pHs 3 and 9.

Synthesis and Study on Effect of Various Chemical Conditions on the Swelling Property of Collagen- g -poly(AA- co -IA) Superabsorbent Hydrogel

In this work, a novel family of salt-responsive polymeric hydrogel based on collagen was prepared via simultaneously graft copolymerization of acrylic monomers, acrylic acid (AA) and itaconic acid (IA) onto collagen backbones by a free radical polymerization technique using ammonium persulfate (APS) as initiator and methylene bisacrylamide (MBA) as a crosslinker. The effect of grafting variables, i.e. AA/IA weight ratio and concentration of MBA and APS, was systematically optimized to achieve a hydrogel with swelling capacity as high as possible. The water absorbency increased with increasing the AA/IA amount in the monomer feed due to formation of polyelectrolyte and then become constant. The swelling of the hydrogel samples in town water and saline solution (0.15 mol/L LiCl,NaCl,KCl, CaCl 2 and AlCl 3 ) was examined. Results indicated that the swelling capacity decreased with an increase charge of cation. This behavior can be attributed to charge screening effect for monovalent cations, as well as ionic crosslinking for multivalent cations.finally,a mechanism for hydrogel formation was proposed and the structure of the product was established using Fourier transform infrared (FTIR) and Scanning Electron Microscopy (SEM) spectroscopies. Also, thermogravimetric analysis showed the thermal stabilities of the hydrogels.

Synthesis and study on effect of various chemical conditions on the swelling property of collagen-g-poly(AA-co-IA) superabsorbent hydrogel

In this work, a novel family of salt-responsive polymeric hydrogel based on collagen was prepared via simultaneously graft copolymerization of acrylic monomers, acrylic acid (AA) and itaconic acid (IA) onto collagen backbones by a free radical polymerization technique using ammonium persulfate (APS) as initiator and methylene bisacrylamide (MBA) as a crosslinker. The effect of grafting variables, i.e. AA/IA weight ratio and concentration of MBA and APS, was systematically optimized to achieve a hydrogel with swelling capacity as high as possible. The water absorbency increased with increasing the AA/IA amount in the monomer feed due to formation of polyelectrolyte and then become constant. The swelling of the hydrogel samples in town water and saline solution (0.15 mol/L LiCl,NaCl,KCl, CaCl2 and AlCl3) was examined. Results indicated that the swelling capacity decreased with an increase charge of cation. This behavior can be attributed to charge screening effect for monovalent cations, as well as ionic crosslinking for multivalent cations.finally,a mechanism for hydrogel formation was proposed and the structure of the product was established using Fourier transform infrared (FTIR) and Scanning Electron Microscopy (SEM) spectroscopies. Also, thermogravimetric analysis showed the thermal stabilities of the hydrogels. Keywords: collagen, hydrogel, acrylic acid, itaconic acid, salt-responsive

Synthesis of pH-Sensitive Hydrogel Based on Starch-Polyacrylate Superabsorbent

In this article, we synthesize of a novel starch-based superabsorbent hydrogel via graft copolymerization of mixtures of acrylic acid (AA) and 2-Hydroxy ethyl methacrylate (HEMA) onto starch backbones. The polymerization reaction was carried out in an aqueous medium and in the presence of ammonium persulfate (APS) as an initiator and N,N’-methylene bisacrylamide (MBA) as a crosslinker. The hydrogel structures were confirmed by FTIR spectroscopy. Furthermore, the swelling of superabsorbing hydrogels was examined in solutions with pH values ranging between 1 and 13. It showed a reversible pH-responsive behavior at pHs 2 and 8. This on-off switching behavior makes the synthesized hydrogels as an excellent candidate for controlled delivery of bioactive agents. A proposed mechanism for hydrogel formation was suggested and the structure of the product was established using FTIR and SEM spectroscopies.

Crosslinked Graft Copolymer of Methacrylic Acid and Gelatin as a Novel Hydrogel with pH-Responsiveness Properties.

In this paper, a novel gelatin-based hydrogel was synthesized through crosslinking graft copolymerization of methacrylic acid (MAA) onto gelatin, using ammonium persulfate (APS) as a free radical initiator in the presence of methylenebisacrylamide (MBA) as a crosslinker. A proposed mechanism for hydrogel formation was suggested and the structure of the product was established using FTIR spectroscopy and gravimetric analysis of the products. Moreover, morphology of the samples was examined by scanning electron microscopy (SEM) and thermogravimetric analysis (TGA/DTG). The effect of reaction variables such as concentration of APS and MBA were systematically optimized to achieve a hydrogel with swelling capacity as high as possible. The gelatin-g-PMAA hydrogel exhibited a pH-responsiveness character so that a swelling-deswelling pulsatile behavior was recorded at pHs 2 and 8. This on-off switching behavior makes the hydrogel as a good candidate for controlled delivery of bioactive agents.