Behavior Of Hydrogels Research Articles

An Eco-Friendly Antheraea Pernyi Silk Gland Protein/Sodium Alginate Multiple Network Hydrogel as Potential Drug Release Systems

To improve the versatility of the sodium alginate-loaded bio-hydrogels, Antheraea pernyi silk gland protein/sodium alginate drug-loaded hydrogels were prepared by using an eco-friendly multiple network cross-link technology. Fourier transform infrared (FT-IR) spectroscopy and UV-Vis spectrophotometer were used separately to evaluate the chemical structure and drug release behavior of drug-loaded hydrogels. The antibacterial drug carrier gels were evaluated by using inhibition zone test against the S. aureus and E. coli. The CCK-8 assay was used to assess the biocompatibility of drug loaded hydrogels. The FT-IR results showed that there was a strong interaction within the drug loaded hydrogels, and the ASGP was beneficial to enhance the interaction within the drug loaded hydrogels. UV-Vis spectrophotometer results indicated the cumulative release reached 80% within 400 min. Antibacterial bio-hydrogels had a good antibacterial property, especially the antibacterial bio-hydrogels with bacitracin exhibits superior to other antibacterial agents. The drug-loaded bio-hydrogels exhibited the adhesion and proliferation of RSC96 cells and perfected biocompatibility. This provides a new idea for further research and development of tissue-friendly drug-loaded biomaterials.

Fabrication and characterization of a bilayered system enabling sustained release of bioflavonoids derived from mandarin biomass

Food-grade hydrogels, those prepared with Generally Recognized as Safe (GRAS) polymers, are promising delivery systems. In this work, alginate hydrogels were studied for their ability to uphold flavonoids laden poly-lactic-co-glycolic acid (PLGA) nanoparticles, and their subsequent release pattern was observed through in vitro gastrointestinal environments. Flavonoids were derived from mandarin peels, and consisted of polymethoxyflavones, chiefly tangeretin and nobiletin, and flavanones, chiefly naringenin. Incorporating these into nanoparticles prepared from GRAS classified PLGA, hereinafter referred to as flavonoids-PLGA nanoparticles, offered the first layer of protection, which were then embedded into alginate hydrogels, offering the second layer of protection. This bilayered system was developed to ensure guarded passage of the bioactives through the severe gastric environment, which would otherwise lead to presystemic metabolism of the flavonoids, rendering them ineffective. The gels were characterised and a 6.0% alginate hydrogel was considered optimal as it offered a dense network, as confirmed by a field emission scanning electron microscope (FE-SEM) image, and a low porosity, which ensured retention of the nanoparticles. Gel rheology revealed the shear thinning behavior of hydrogels, and high resistance to deformation was observed for 6% hydrogel when subjected to a load of 500N. Subjecting the ensemble to gastrointestinal environments showed a negligible 4.0% release of flavonoids in the first 2 hours of the gastric phase, followed by a sustained release through the next 10 hours in the intestinal environment, as confirmed by mass spectrometry (MS) profiles. Confocal laser scanning microscope (CLSM) images of the hydrogel clearly revealed the pH-responsive swelling and release of the nanoparticles from the hydrogel in the intestinal phase. It is envisaged that these, and other similar findings, would eventually manifest into ‘functional hydrogels’ delivery systems that bear the ability to incorporate nutraceuticals whilst retaining their functionality, as viable products in the near future.

Effect of Salt on Dynamic Mechanical Behaviors of Polyampholyte Hydrogels

Understanding the dynamic mechanical behaviors of tough hydrogels with ionic dynamic bonds in saline solution is crucial for applications, particularly in the biomedical field. In this work, using polyampholyte hydrogels, dually crosslinked with a primary network from covalent crosslinkers and/or trapped entanglements, and a dynamic network from ionic bonds, as a model system, we investigate the salt effect on rheological response and mechanical behaviors. Through a systematic study on one gel without a chemical crosslinker and one gel with a chemical crosslinker, we demonstrate that the salt effect on mechanical properties, including small-strain moduli, large deformation energy dissipation, and fracture stretch ratio, can be effectively converted into frequency or strain rate dependences following the time–salt superposition principle. Accordingly, we access a wide range of observation time scales from 10–11 to 102 rad/s at room temperature, covering three regimes: (I) the high-frequency plateau regime from the dynamic and primary networks, (II) the viscoelastic regime from sticky Rouse motion of ionic associations, and (III) the low-frequency plateau regime from the primary network. Moreover, we disclose an in-depth understanding of the entanglement’s behavior in the long-timescale regime III. This work not only provides a guide to biological applications of hydrogels in saline environments but also gives important insights into the toughening mechanism via dynamic bonds in other systems with dually crosslinked structures.

Synthesis, Characterization, and Digital Light Processing of a Hydrolytically Degradable Hyaluronic Acid Hydrogel.

Numerous chemical modifications of hyaluronic acid (HA) have been explored for the formation of degradable hydrogels that are suitable for a variety of biomedical applications, including biofabrication and drug delivery. Thiol-ene step-growth chemistry is of particular interest due to its lower oxygen sensitivity and ability to precisely tune mechanical properties. Here, we utilize an aqueous esterification route via reaction with carbic anhydride to synthesize norbornene-modified HA (NorHACA) that is amenable to thiol-ene crosslinking to form hydrolytically unstable networks. NorHACA is first synthesized with varying degrees of modification (∼15-100%) by adjusting the ratio of reactive carbic anhydride to HA. Thereafter, NorHACA is reacted with dithiol crosslinker in the presence of visible light and photoinitiator to form hydrogels within tens of seconds. Unlike conventional NorHA, NorHACA hydrogels are highly susceptible to hydrolytic degradation through enhanced ester hydrolysis. Both the mechanical properties and the degradation timescales of NorHACA hydrogels are tuned via macromer concentration and/or the degree of modification. Moreover, the degradation behavior of NorHACA hydrogels is validated through a statistical-co-kinetic model of ester hydrolysis. The rapid degradation of NorHACA hydrogels can be adjusted by incorporating small amounts of slowly degrading NorHA macromer into the network. Further, NorHACA hydrogels are implemented as digital light processing (DLP) resins to fabricate hydrolytically degradable scaffolds with complex, macroporous structures that can incorporate cell-adhesive sites for cell attachment and proliferation after fabrication. Additionally, DLP bioprinting of NorHACA hydrogels to form cell-laden constructs with high viability is demonstrated, making them useful for applications in tissue engineering and regenerative medicine.

Photoreactive Hydrogels Based on Type I Collagen Extracted from Different Sources as Scaffolds for Tissue Engineering Applications: A Comparative Study

Collagen-based hydrogels are promising constructs used frequently as scaffolds in various tissue engineering applications. The source of collagen extraction can influence the physiochemical properties, mechanical strength, as well as cellular behaviour of the tissue-engineered hydrogels. In the present study, type I collagen was isolated from three different animal sources, namely bovine Achilles tendon, bighead carp fish skin, and rat tail tendons. After characterizing the extracted collagens, their structures were modified via covalent functionalization of the free amines with methacrylate groups. Methacrylated collagens were combined with PEG-diacrylate to act as three-dimensional photocrosslinked scaffolds for culturing human corneal stromal cells. Physicochemical properties, mechanical strength, morphological features, and cellular behaviour were different depending on the collagen sources. Human corneal stromal cells more easily penetrated within hydrogels containing rat tail type I collagen, which also had greater pore sizes and porosity. However, the expressions of type I collagen and lumican were observed to be a greater extent in fish skin collagen-based hydrogels. Such observations highlight the significant effect of collagen extraction source on cellular behaviour and the importance of having a proper selection in accordance with the application of the tissue-engineered scaffold.

Dough rheological properties, texture, and structure of high-moisture starch hydrogels with different potassium-, and calcium-based compounds

The effects of four kinds of potassium- (potassium alginate, PA; potassium dihydrogen phosphate, KDP) and calcium-based (calcium carbonate, CC; calcium silicate, CSi) compounds on the pasting behavior, rheological properties, microstructure, water mobility, and textural characteristics of pastes, dough, and high-moisture starch hydrogels from potato starch were evaluated. The results showed that the addition of 0.5% CSi, 0.5% CC, 0.4% PA and 0.4% KDP (w/w, total starch basis) significantly improved the tensile strength of high-moisture starch hydrogels compared to that of pure potato starch. Further discussion about the mechanism revealed that the addition of these components could reduce the swelling capacity and peak viscosity of potato starch during heating, further enhance the network structure of the starch dough, and reduce the water mobility thereof, thus contributing to a compact stacking of starch and smaller and denser pore structure of the high-moisture starch hydrogels. This study provides a theoretical basis for the formulation design of alum-free hydrogel derived products.

Investigation of the time-dependent friction behavior of polyacrylamide hydrogels

Hydrogels have attracted enormous frictional investigation owing to their great potential in hydration lubrication. Researchers have revealed that the lubrication behavior of hydrogel depends on a number of parameters such as contact area, sliding velocity, and solution condition. However, less effort has been devoted to understanding the time-dependent friction behavior of polymeric hydrogels. In this work, the time-dependent behavior of hydrogel friction was systematically investigated through three typical polyacrylamide hydrogels (PAM, PAM-PEI, and PAM-PAA) on a rheometer. Interestingly, the friction coefficients (μ) of the hydrogels varied with time, and two distinct regimes (viz., the friction-decrease regime and friction-constant/increase regime) were observed. In the friction-decrease regime, all the friction coefficients for the three PAM-based hydrogels dramatically decreased (e.g. μ decreased from ∼ 0.107 to ∼ 0.034 for PAM, μ decreased from ∼ 0.059 to ∼ 0.021 for PAM-PAA). The decrease of friction coefficients can be explained by frictional relaxation mechanism, where the deformation of polymers in the shear direction and the desorption of polymer chains from solid surface play dominant roles. Tribological results show that the increase in friction is determined by the charge behavior and polymer network of the PAM-based hydrogels. Besides, shear velocity and pH of the solution also significantly affected the friction behavior of hydrogels on the glass substrate. The understanding of the time-dependent friction behavior of PAM hydrogels provides insights to develop water-based lubricants with engineering applications.

Dual drug-loaded hydrogels with pH-responsive and antibacterial activity for skin wound dressing

Antibacterial and hemostatic properties are essential for wound healing dressing. In this study, a new type of hydrogel composed of gelatin methacryloyl (GelMA) and hyaluronic acid-aldehyde (HA-CHO) is fabricated by photo-crosslinking and respectively loaded with a single drug gentamicin sulfate (GS), and two drugs of GS and lysozyme (LZM). The composite hydrogel of GelMA and HA-CHO is successfully synthesized by the aldehyde and Schiff base reactions. The structures and compositions of the hydrogels with and without drug loaded are characterized by FT-IR, 1H NMR, and XPS. Furthermore, the microstructure and swelling behaviour of hydrogels prove that the content of HA-CHO has a significant role in the formation of hydrogels with dense porous structures and super absorbent. pH 7.4 and pH 5.0 conditions are used to evaluate the drug release behaviour of the obtained hydrogels. The released amount of GS of the drug-loaded hydrogels in the acidic buffer is more than that of the physiological environment because of the cleaved Schiff base bonds and the electrostatic interaction. Especially for the dual drug-loaded hydrogel GelMA/HA-CHO/GS/LZM, the released ratio of GS is elevated from 59 % in pH 7.4 buffer to about 78 % in pH 5.0 buffer within the first 6 h, which verifies the excellent pH-stimulus responsiveness. These endow the GS-LZM dual drug-loaded hydrogels with superior antibacterial efficiencies to that of the single GS drug-loaded hydrogels, no drug-loaded hydrogels, and SEBS control, especially in inhibiting S. aureus in a lower concentration of 106 CFU mL−1, which can be attributed to the synergistic effect of LZM and GS. For S. aureus at 106 CFU mL−1, the bacterial survival of GelMA/HA-CHO/GS/LZM is 1.1 %, which shows outstanding antibacterial effect. Hence, the drug-loaded hydrogels, especially the dual drug-loaded hydrogels with pH-responsive, antibacterial, and hemostatic properties have great potential as wound healing materials.

Entirely S-protected thiolated hydroxyethylcellulose: Design of a dual cross-linking approach for hydrogels

AimThe aim of this study was the synthesis and evaluation of entirely S-protected thiolated hydroxyethylcellulose (HEC) with low and high viscosity, as well as thiolated poly-L-lysine (poly-L-Lys) used as dual-acting ionic as well as thiol-disulfide exchange mediated cross-linking hydrogel. MethodsBis(mercaptosuccinic acid) was covalently attached to low and high viscous HECs via Fisher esterification, obtaining S-protected polymers. Poly-L-Lys-cysteine was synthesized via amidation of poly-L-Lys-HBr with cysteine (Cys). Thiolated polymers were examined in terms of cytotoxicity and rheological behavior of hydrogels containing these thiomers was evaluated with a cone-plate rheometer. ResultsThiomers showed less cytotoxicity compared to the corresponding unmodified polymers. Rheological studies showed that cross-linking occurred between the two polymers via thiol-disulfide exchange reactions facilitated by the complementary charges. Employing poly-L-Lys-Cys in a concentration of either 0.5 or 5% (m/v) resulted in a 34.5-fold or 17.3-fold as well as a 53.6-fold or 29.6-fold improvement in dynamic viscosity within 5 min at 37 °C on S-protected thiolated low and high viscous HEC, compared to the corresponding unmodified HECs, respectively. ConclusionBy the combination of anionic S-protected thiolated polymers with a cationic thiolated polymer, dual-acting hydrogels exhibiting a time dependent increase in viscosity can be designed.

Mixed gels based on low acyl gellan and citrus pectin: A linear viscoelastic analysis

This research aimed to analyze the viscoelastic behavior of mixed hydrogels based on low methoxyl citrus pectin (DE = 30.4%) and low acyl gellan, in the presence of calcium ions to assess the effect of each polysaccharide on the gelation and relaxation processes of the mixed systems. Linear viscoelastic properties were determined, and the experimental data were used to fit the generalized Maxwell model to obtain the hydrogels' relaxation times and average network mesh size. In most mixed gels, the co-gelification of gellan and pectin provided more rigid hydrogels characterized by narrow meshes (6.1–11.7 nm) and slower rearrangements of polymer chains (relaxation times (λ) between 16.7 and 55.2 s) compared to gellan gels (λ = 18.4–29.3 s). The viscoelastic behavior of the pectin-gellan gels suggests a macromolecular network organization where gellan junction zones predominate, and pectin contributes to reinforcing the mixed network. That organization generates more macromolecular interactions via calcium bridges and hydrogen bonds, promoted by the accessibility of anionic sites in both biopolymers and the low extent of branching (7 mol%) of pectin. The rheological analysis provides a new understanding concerning the hybrid pectin-gellan networks, which can be used to design new natural hydrogels for diverse applications such as biocompatible biomaterials and delivery vehicles.

Kinetics models for polyacrylamide‐graphene oxide composites as antifoulant

AbstractAntifouling paints are used to protect the surface against these organisms such as algae, sea squirts, and barnacles. According to previous research, fish and seaweeds do not adhere to submerged surfaces using wet and soft hydrogels. The aim of this study is to investigate the temperature effect on the performance of antifouling composites to develop new useful antifouling composites for shipping sector. In this swelling experiment, the behavior of hydrogels produced from polyacrylamide (PAAm) and graphene oxide (GO) was investigated at different temperatures. Free‐radical cross‐linking copolymerization formed composite, using acrylamide, ammonium persulfate, N, N′‐methylenebisacrylamide (BIS, Merck), and graphene oxide with various contents. The steady‐state fluorescence technique was used for studying the swelling of PAAm‐GO composites at various temperatures in pure water. When pyranine fluorescence intensity, I was measured, it decreased until swelling equilibrium was achieved. After the swelling experiment was started, the fluorescence emission (Iem) and scattering light intensities, Isc from different GO content hydrogels were observed by real‐time monitoring at various temperatures. Li‐Tanaka and Fickian models were used to determine the diffusion coefficients for the swelling experiments in distilled and Marmara Sea Water for 8 and 50 μl of GO content hydrogels, respectively. According to literature, PAAm is utilized as a surface coating material to reduce biofouling, for this reason, this research will show a way to be able to use PAAm inside antifouling paints material for the marine industry.

Magnetic Resonance Imaging: Time-Dependent Wetting and Swelling Behavior of an Auxetic Hydrogel Based on Natural Polymers.

A time-dependent understanding of swelling characteristics and external stimuli behavior is crucial for the development and understanding of functional hydrogels. Magnetic resonance imaging (MRI) offers the opportunity to study three-dimensional (3D) soft materials nondestructively. This technique is already widely used as an image-based medical diagnostic tool and is applied here to evaluate complex structures of a hydrogel-a double network of chemically crosslinked casein enhanced with alginate-fabricated by 3D printing. When hydrogel disks immersed in four different liquid systems were analyzed, the material exhibited distinct system-dependent behavior characterized by rheological and mechanical measurements. Further material functionalization was achieved by macroscopic structuring of the hydrogel as an auxetic material based on a re-entrant honeycomb structure. MRI offers the advantage of monitoring overall changes in the area of the analyzed specimen and internal structural changes simultaneously. To assess the behavior of this complex structure, a series of short MRI measurements, each lasting 1.7 min, captured liquid diffusion and thus structural swelling behavior. A clear dependence of external and internal structural changes as a function of liquid properties causing these changes was observed. In conclusion, this approach might pave the way for prospective applications to monitor liquid diffusion into (e.g., vascularization) and swelling behavior of functional hydrogels.

Simulations Explain the Swelling Behavior of Hydrogels with Alternating Neutral and Weakly Acidic Blocks

We used computer simulations to study the equilibrium swelling of weak (pH-responsive) polyelectrolyte hydrogels as a function of pH and salt concentration in a supernatant solution. Our simulations were designed to represent recently synthesized gels composed of tetrapoly(acrylic acid) and tetrapoly(ethylene glycol) stars. To model the ionization equilibrium of the weak acid groups and the exchange of small ions with the reservoir, we applied the recently developed grand-reaction Monte Carlo method. We showed that the ionization of these gels as a function of the pH significantly deviates from the ideal Henderson–Hasselbalch equation due to two main contributions: (1) electrostatic interactions and (2) Donnan partitioning of small ions. The first contribution dominates in the gels composed of alternating neutral and acidic blocks, contrasting with our previous observations that both contributions are comparably strong in hydrogels composed of homogeneously distributed weak acid groups. We also critically examined the counterion condensation argument, previously invoked to explain why the experimentally observed swelling was lower than predicted by theory. Thus, a detailed analysis of the simulations allowed us to understand which of the above effects dominates in different systems and why, thereby allowing us to identify the correct physical origin of the deviations from ideal swelling. Such an understanding is important not only for correctly interpreting experimental measurements but also for designing polyelectrolyte gels tailored to exhibit specific swelling response to pH and salt concentration.

Chitosan based hybrid hydrogels for drug delivery: Preparation, biodegradation, thermal, and mechanical properties

AbstractIn the present paper, biodegradable hybrid hydrogels were prepared by using chitosan as a natural polymer and polyurethane containing azomethine as a synthetic polymer for the drug delivery application for 5‐fluorouracil. The fabricated hydrogels were characterized via FT‐IR and SEM analysis. Besides, the thermal, mechanical, and wettability properties, water uptake, biodegradation, protein absorption, drug loading, and release behaviors of the hybrid hydrogels were studied. The obtained results indicated that the fabricated hybrid hydrogels have exhibited good mechanical, hydrophilic, water uptake, and biodegradation behaviors. The hybrid hydrogels also showed 50% drug release amounts and they could be a good candidate for the controlled delivery of 5‐FU due to these properties.

Large amplitude oscillatory shear behavior of thermoresponsive hydrogels: Single versus double network

Double network (DN) hydrogels have been recognized as new tough materials for several industries due to their precise structural platforms and significant properties. However, a comprehensive understanding of microstructural changes of DN hydrogels under large deformations is required to extend their applications. In this work, we use the large amplitude oscillatory shear (LAOS) technique to study the nonlinear response of a thermoresponsive κ-carrageenan/polyacrylamide DN system and its nanocomposite containing graphene oxide (GO) in comparison to its single network components. The results show a combination of strain stiffening and shear thickening nonlinear responses. The elastic intracycle strain stiffening was mainly attributed to the shear-induced increase in the elasticity of network chains and non-Gaussian stretching of individual chains. In addition, the orientation of the κ-carrageenan double helix segments and their enhancing effect on molecular orientation could be proposed as another possible mechanism of strain stiffening. The viscous intracycle shear thickening is also interpreted by two mechanisms of shear-induced temporary structure formation and reformation of dissociated physical interactions. It is also found that the GO nanosheets could contribute to the viscoelastic response by increasing the molecular interactions and, thus, amplification of energy dissipation. Furthermore, temperature dependency of the DN hydrogel owing to the conformational changes of the κ-carrageenan network at sufficiently high temperatures is used to investigate the effect of temperature on nonlinear behaviors. Increasing the temperature is found to have a significant decreasing effect on viscous nonlinearity, while its effect on the elastic nonlinearity was strongly dependent on the strain amplitude. This study provides a better understanding of the correlation between the microstructure and viscoelastic properties for designing tough hydrogels.

Effect of sodium dodecyl sulfate on shape‐memory properties of side‐chain crystalline hydrogel via micellar copolymerization

AbstractA chemical shape‐memory hydrogel containing crystalline structure is prepared via micellar copolymerization of hydrophilic monomer acrylamide (AM) and hydrophobic monomer octadecyl acrylate (C18) in a sodium dodecyl sulfate (SDS) solution. The influence of SDS on the shape‐memory behavior of hydrogel investigated by differential scanning calorimetry (DSC) and Temperature‐dependent X‐ray indicate that the melting and crystallization peaks derived from the thermal properties of C18 units is different from peaks corresponding to the pure SDS. In addition, the microstructure evolution information of hydrogels dose not change upon heating process, regardless of the presence or absence of SDS. Therefore, only the hydrophobic associations formed by C18 blocks play a decisive role in the shape memory function of hydrogel system. The difference between the transition process (from temporary shape to permanent shape) of hydrogel with and without SDS at different temperature is because that the hydrophobic region of side chain crystallization of SDS‐free hydrogel may escape the restriction of SDS and become more sensitive to temperature, they can preferentially return to their initial shape under the same time and temperature than SDS‐containing gels. Whether SDS exists only affect the speed of shape memory behavior, but not the microstructure evolution of hydrogel system.

Photothermal nanohybrid hydrogels for biomedical applications.

In the past decades, diseases such as wound infection, cancer, bone defect and osteoarthritis have constantly threatened the public health. However, the traditional treatment has many insufficiencies, such as high cost, easy recurrence and high biological toxicity. Hydrogel is a material with three-dimensional network structure, which has a series of advantages, such as injectability, self-heal ability, easy loading and controllability of drug release, and excellent biocompatibility. Therefore, it is extensively used in drug delivery, antibacterial, anti-cancer and other fields. However, the traditional hydrogels have the single performance, and therapeutic efficacy is often rely on the drugs loaded on them to cure diseases, which cannot achieve sustainable therapeutic effect. In order to solve this problem, photothermal nano hydrogel with photothermal agent (PTA) has become an ideal material due to its excellent physical and chemical properties. Photothermal nano hydrogels used in photothermal therapy (PTT) can exploit the photothermal effect of photothermal agent to increase local temperature and control the sol-gel phase transition behavior of hydrogels, so they are widely used in drug release, photothermal sterilization, photothermal inhibition of cancer cells and enhancement of bone repair. To sum up, this paper introduces the preparation of hydrogels with photothermal nanomaterials, and discusses their applications in the fields of drug release, photothermal sterilization, photothermal cancer cell inhibition and enhanced bone repair.

A micromechanical model for the swelling effect on visco-super-elastic and damage self-healing behaviors of hydrogels reinforced by nanoparticles

In the present article, a micromechanical model is developed for the visco-super-elastic behavior of swollen hydrogel-based nanocomposites. The model formulated in a finite strain context introduces explicitly the hydrogel network features in terms of swelling and dynamic breaking-recombination. The effective interactions between the nanoparticles and the swollen hydrogel network are considered using a micro-macro scale transition within the Eshelby inclusion theory. The model is compared to experimental observations of a high-swelling capacity hydrogel-based nanocomposite reinforced with different concentrations of nanoparticles. The model is firstly identified using experimental data at an initial swelling state in terms of stress-strain response, energy dissipation and ultimate properties. The predictive capability of the model is then verified on a wide range of swelling ratios for a given nanofiller concentration. The efficiency of the model is further critically discussed by comparisons with history-dependent data under stretching-retraction and self-healing. The effects of nanoparticles and swelling on the self-healing behavior are shown thanks to the model.

Mesenchymal stem cells encapsulation in chitosan and carboxymethyl chitosan hydrogels to enhance osteo-differentiation.

Recently biomaterials utilized for designing scaffolds in tissue engineering are not cost-effective and eco-friendly. As a result, we design and develop biocompatible and bioactive hydrogels for osteo-tissue regeneration based on the natural polysaccharide chitosan. Three distinct hydrogel components were used for this. Hydrogels networks were created using chitosan 2% (CTS 2%), carboxymethyl chitosan 2% (CMC 2%), and 50:50 mixtures of CTS and CMC (CTS/CMC 50:50). Furthermore, scanning electron microscopy (SEM), Fourier transforms infrared spectroscopy (FTIR), degradation, and swelling behavior of design hydrogels were studied. Also, the cytocompatibility and osteo-differentiation potency were examined by encapsulating mesenchymal stem cells derived from adipose tissue (AMSCs) on the designed hydrogels. According to the findings, our results showed an acceptable pore structure, functional groups, and degradation rate of the designed hydrogels for in vitro evaluation. In addition, employing CMC instead of CTS or adding 50% CMC to the hydrogel component could improve the hydrogel's osteo-bioactivity without the use of external osteogenic differentiation agents. The CMC-containing hydrogel not only caused early osteogenesis but also accelerated differentiation to the maturity phase of osteoblasts.

Gelation and the Self-Healing Behavior of the Chitosan-Catechol Hydrogel.

Mussel-inspired adhesive hydrogels have been developed in biomedical fields due to their strong adhesive property, cohesive capability, biocompatibility, and hemostatic ability. Catechol-functionalized chitosan is a potential polymer used to prepare adhesive hydrogels. However, the unique gelation mechanism and self-healing properties of catechol-grafted chitosan alone have not yet been explored. Herein, catechol-grafted chitosan (CC) was synthesized and further concentrated to obtain the self-healing CC hydrogels. The gelation mechanism of CC hydrogels may be attributed to the formation of hydrogen bonding, cation-π interactions, Michael addition, or Schiff base reactions during concentration phases. Rheological studies showed that the CC hydrogel owned self-healing properties in repeated damage-healing cycles. Coherent small-angle X-ray scattering (SAXS) analyses revealed the formation of a mesoscale structure (~9 nm) as the solid content of the hydrogel increased. In situ SAXS combined with rheometry verified the strain-dependent behavior of the CC hydrogel. The CC hydrogel displayed the osmotic-responsive behavior and enhanced adhesive strength (0.38 N/cm2) after immersion in the physiological saline. The CC scaffold prepared by lyophilizing the CC hydrogel revealed a macroporous structure (~200 µm), a high swelling ratio (9656%), good compressibility, and durability. This work provides an insight into the design of using chitosan-catechol alone to produce hydrogels or scaffolds with tunable mechanical properties for further applications in biomedical fields.