Biocomposite Hydrogels Research Articles

Innovative Approach to Accelerate Wound Healing: Synthesis and Validation of Enzymatically Cross-Linked COL-rGO Biocomposite Hydrogels.

In this study, an innovative conductive hybrid biomaterial was synthetized using collagen (COL) and reduced graphene oxide (rGO) in order for it to be used as a wound dressing. The hydrogels were plasticized with glycerol and enzymatically cross-linked with horseradish peroxidase (HRP). A successful interaction among the components was demonstrated by FTIR, XRD, and XPS. It was demonstrated that increasing the rGO concentration led to higher conductivity and negative charge density values. Moreover, rGO also improved the stability of hydrogels, which was expressed by a reduction in the biodegradation rate. Furthermore, the hydrogel's stability against the enzymatic action of collagenase type I was also strengthened by both the enzymatic cross-linking and the polymerization of dopamine. However, their absorption capacity, reaching values of 215 g/g, indicates the high potential of the hydrogels to absorb fluids. The rise of these properties positively influenced the wound closure process, achieving an 84.5% in vitro closure rate after 48 h. These findings clearly demonstrate that these original composite biomaterials can be a viable choice for wound healing purposes.

Synthesis and characterization of SiO2 nanoparticles reinforced 3D printable gelatin/PVA/guar gum/ hydroxypropyl methylcellulose-based biocomposite hydrogel

Biocomposite-based hydrogels have engrossed snowballing devotion due to their hydrophilic, biodegradability, and biocompatibility properties. 3D printing of biocomposite-based hydrogels has emerged in numerous fields, such as pharmaceutical, biomedical, and food engineering, as it involves fabricating complex and customized geometrical components. The present works focus on developing new 3D printable biocomposite hydrogels using gelatin, polyvinyl alcohol, guar gum, and hydroxypropyl methylcellulose (HMC). Hydroxyapatite (HAp) and SiO2 nanoparticles are used as supplemental materials to tailor the properties of hydrogels. The composition has been optimized for enhanced printability through rheological characterization. The developed hydrogel, chemically cross-linked with glyoxal, has been assessed for its static and dynamic mechanical properties, swelling, thermal stability, and degradation characteristics. By incorporating supplements such as HAp, HMC, and SiO2 into the gelatin/polyvinyl alcohol (PVA)/guar gum hydrogel, a compressive and tensile strength of 4.64 MPa, and 71.76 kPa was achieved with better recovery efficiency under cyclic compression and tensile tests. The highest storage modulus of 0.6 MPa at 100 Hz was noticed. A sorbing capacity of 208.98 % was perceived in 70 h. The hydrogel demonstrated quick creep recovery and stress relaxation properties with faster degradation behavior than the PVA hydrogel. Based on the outcomes attained in the present study, it is inferred that the reported biocomposite hydrogels are promising materials for pharmaceutical and biomedical applications.

Improving Antimicrobial Properties of GelMA Biocomposite Hydrogels for Regenerative Endodontic Treatment.

Regenerative endodontics is a developing field involving the restoration of tooth structure and re-vitality of necrotic pulp. One of the most critical clinical considerations for regenerative endodontic procedures is the disinfection of the root canal system, since infection interferes with regeneration, repair, and stem cell activity. In this study, we aimed to provide the synthesis of injectable biopolymeric tissue scaffolds that can be used in routine clinical and regenerative endodontic treatment procedures using Gelatin methacryloyl (GelMA), and to test the antimicrobial efficacy of Gelatin methacryloyl/Silver nanoparticles (GelMA/AgNP), Gelatin methacryloyl/Hyaluronic acid (GelMA/HYA), and Gelatin methacryloyl/hydroxyapatite (GelMA/HA) composite hydrogels against microorganisms that are often encountered in stubborn infections in endodontic microbiology. Injectable biocomposite hydrogels exhibiting effective antimicrobial activity and non-cytotoxic behavior were successfully synthesized. This is also promising for clinical applications of regenerative endodontic procedures with hydrogels, which are proposed based on the collected data. The GelMA hydrogel loaded with hyaluronic acid showed the highest efficacy against Enterococcus faecalis, one of the stubborn bacteria in the root canal. The GelMA hydrogel loaded with hydroxyapatite also showed a significant effect against Candida albicans, which is another bacteria responsible for stubborn infections in the root canal.

Tannic acid modified keratin/sodium alginate/carboxymethyl chitosan biocomposite hydrogels with good mechanical properties and swelling behavior

Natural polymer-based hydrogels have demonstrated great potential as wound-healing dressings. They help to maintain a moist wound environment as well as promote faster healing. In this work, a multifunctional hydrogel was prepared using keratin, sodium alginate, and carboxymethyl chitosan with tannic acid modification. Micro-morphology of hydrogels has been performed by scanning electron microscopy. Fourier Transform Infrared Spectroscopy reveals the presence of hydrogen bonding. The mechanical properties of the hydrogels were examined using a universal testing machine. Furthermore, we investigated several properties of the modified hydrogel. These properties include swelling rate, water retention, anti-freezing properties, antimicrobial and antioxidant properties, hemocompatibility evaluation and cell viability test in vitro. The modified hydrogel has a three-dimensional microporous structure, the swelling rate was 1541.7%, the elastic modulus was 589.74 kPa, the toughness was 211.74 kJ/m3, and the elongation at break was 75.39%, which was similar to the human skin modulus. The modified hydrogel also showed inhibition of S. aureus and E. coli, as well as a DPPH scavenging rate of 95%. In addition, the modified hydrogels have good biological characteristics. Based on these findings, the K/SA/CCS hydrogel holds promise for applications in biomedical engineering.

Biocomposite silk fibroin hydrogel with stretchability, conductivity and biocompatibility for wireless strain sensor

As a natural biopolymer material, silk fibroin with unique mechanical properties can be used in the preparation of biocomposite hydrogels for strain sensors. But, the electromechanical properties of biocomposite hydrogel strain sensors are still insufficient, such as the deterioration of electrical signals and low sensitivity, which need to develop a hydrogel with a stable transmission network for electric conduction. Herein, a silk fibroin biocomposite hydrogel is prepared by incorporating tannic acid and MXene nanosheets into a polyacrylamide and silk fibroin double network. The electromechanical properties of hydrogels are improved by optimizing the proportion of material components. As a result, the double network structure and supramolecular interaction enhance the stretchability of hydrogels (692% fracture strain). The hydrogel also exhibits good biocompatibility and conductivity (0.85 S/m), which shows the application prospect in wearable sensors. The wireless strain sensor assembled by this biocomposite hydrogel presents good portability and sensing performance, such as high sensitivity (gauge factor = 6.04), wide working range (500% strain), and outstanding stability (1000 cycles at 100% strain). The results indicate that the hydrogel strain sensor can be used to monitor human body movement. The biocomposite hydrogel is expected to be applied in the field of wearable strain sensors, and this study can provide a new way for the design of flexible electronic materials.

Influence of ZnO Nanoparticles on the Properties of Ibuprofen-Loaded Alginate-Based Biocomposite Hydrogels with Potential Antimicrobial and Anti-Inflammatory Effects.

Hydrogels are a favorable alternative to accelerate the burn wound healing process and skin regeneration owing to their capability of absorbing contaminated exudates. The bacterial infections that occur in burn wounds might be treated using different topically applied materials, but bacterial resistance to antibiotics has become a major problem worldwide. Therefore, the use of non-antibiotic treatments represents a major interest in current research. In this study, new antibiocomposite hydrogels with anti-inflammatory and antimicrobial properties based on hyaluronic acid (HA) and sodium alginate (AG) were obtained using 4-(4,6-dimethoxy-1,3,5-triazinyl-2)-4-methylmorpholinium chloride as an activator. The combination of Ibuprofen, a non-steroidal anti-inflammatory drug commonly used to reduce inflammation, fever and pain in the body, with zinc oxide nanoparticles (ZnO NPs) was used in this study aimed at creating a complex hydrogel with anti-inflammatory and antimicrobial action and capable of improving the healing process of wounds caused by burns. FTIR spectra confirmed the cross-linking of AG with HA as well as the successful incorporation of ZnO NPs. Using electronic microscopy, it was noticed that the morphology of hydrogels is influenced by the incorporation of ZnO nanoparticles. Moreover, the incorporation of ZnO nanoparticles into hydrogels also has an influence on the swelling behavior at both pH 7.4 and 5.4. In fact, the swelling rate is lower when the amounts of the activator, HA and ZnO NPs are high. A drug release rate of almost 100% was observed for hydrogels without ZnO NPs, whereas the addition of nanoparticles to hydrogels led to a decrease in the release rate to 68% during 24 h. Cellular viability tests demonstrated the non-cytotoxic behavior of the hydrogels without the ZnO NPs, whereas a weak to moderate cytotoxic effect was noticed for hydrogels with ZnO NPs. The hydrogels containing 4% and 5% ZnO NPs, respectively, showed good antimicrobial activity against the S. aureus strain. These preliminary data prove that these types of hydrogels can be of interest as biomaterials for the treatment of burn wounds.

Effect of Keratin-Based Biocomposite Hydrogels as a RhBMP-2 Carrier in Calvarial Bone Defects Mouse Model

Effect of Keratin-Based Biocomposite Hydrogels as a RhBMP-2 Carrier in Calvarial Bone Defects Mouse Model

Effect of the Welan Gum Concentration on the Rheological and Structural Behaviour of Biocomposite Hydrogels with Sepiolite as Filler.

A very positive and effective approach to tuning the mechanical properties of polymers has been the development of composites. This paper deals with novel biocomposite hydrogels composed by two biocompatible materials: welan gum as biopolymer matrix and sepiolite as filler. Welan gum content was studied as a tuning parameter to control the rheological properties of the developed biocomposites. The rheological and microstructural behaviour of the composites was investigated by mean of steady-state flow curves, creep-recovery tests, small amplitude oscillatory shear tests, and electron microscopy. An increase in welan gum content provoked the progressive disappearance of the shear-thinningzero-shear-thinning behaviour with a yield point which was clearly defined, characteristic of sepiolite gels, leading to a conventional shear-thinning behaviour, typical of polymeric systems. Also, a higher content of biopolymer in the mixtures led to a more elastic and compact structure characterized by higher values of both G' and G". The fundamental novelty was based on taking the flowability provided by the biopolymer as the main objective and reinforcing the viscosity yielded by welan gum with sepiolite, which contributed to increasing the biocomposite consistency. Thus, rheological properties can be adjusted, taking into account the balance of the components to adapt them to the requirements of each application.

Skin-inspired injectable adhesive gelatin/HA biocomposite hydrogel for hemostasis and full-thickness dermal wound healing.

An insufficient adhesion to wet surfaces and biased functions for therapeutic efficacy are limitations to the application of gelatin and hyaluronic acid. Herein, we developed a simple double-injection approach to prepare a skin-inspired gelatin/HA-based injectable remoistenable adhesive hydrogel (HI/DA-Gel) through a simultaneous crosslinking and bio-compositing strategy of genipin incorporated with dopamine (DA) grafted gelatin and N-hydroxy succinimide (NHS) merged with hyaluronic acid. The integrative crosslinking and bio-compositing strategy led to the formation of a HI/DA-Gel with a highly skin-bionic interconnected internal double network 3D-structure with elevated surface wettability, thermal-stablity, adhesive and mechanical properties as expected. In vitro/in vivo biostudies showed that HI/DA-Gel enhanced collagen deposition, hemostatic effects and upregulated the production of CD31, showing an effective hemostasis and full-thickness dermal wound healing strategy. This work proposes a novel facile double-injection approach for the design of gelatin/ hyaluronic acid multi-functional injectable bio-composite hydrogels for integrated therapeutic effects.

PEG-DA/Conconavalin A Biyokompozit Hidrojel Sentezi ve Kanser Tedavisi İçin Araştırılması

Drug therapy is an important research area in cancer treatment. Conconavalin a (ConA) is a lectin used for anti-cancer drug research because it can interact with cancer cells. In this study, hydrogels was synthesized using ConA and polyethylene glycol diacrylate (PEGDA). Synthesized hydrogels were characterized by Fourier-Transform Infrared Spectroscopy (FTIR) and the Scanning Electron microscope (SEM). When we examined at the characterization of hydrogels, it was observed that PEGDA/ConA was integrated and that biocomposites were synthesized. Dynamic swelling behavior of synthesized hydrogels were studied at pH = 7.4 and 1.2. When we examined the swelling behavior of synthesized PEGDA/ConA hydrogels, it was observed that biocomposite hydrogels reached maximum in approximately 60 minutes. PEGDA/ConA hydrogels were loaded gentamisin, a broad spectrum antibiotic,and drug release behavior of gentamicin loaded hydrogels at pH=7.4 and pH=1.2 were investigated and compared. Considering the drug release behavior of PEGDA/ConA biocomposite hydrogels at pH=1,2, it was observed that the drug release was around 15-20% in 400 minutes, and that the drug release was around 60% in 400 minutes at pH=7,4. It has been found that its design is suitable as a drug delivery system that can be used in long-term release studies. Thus, it has been seen that PEGDA/ConA hydrogels can be used in anti-cancer drug release.

Nanocage Ferritin Reinforced Polyacrylamide Hydrogel for Wearable Flexible Strain Sensors.

Biocomposite hydrogels are promising for applications in wearable flexible strain sensors. Nevertheless, the existing biocomposite hydrogels are still hard to meet all requirements, which limits the practical application. Here, inspired by the structure and composition of natural ferritin, we design a PAAm-Ferritin hybrid hydrogel through a facile method. Ferritin is uniformly distributed in the cross-linking networks and acts as a nanocage spring model, leading to the enhanced tensile strength of the hydrogel. The fracture stress is 99 kPa at 1400% maximum elongation. As fabricated PAAm-Ferritin hybrid hydrogels exhibit high toughness and low elastic modulus (21 kPa). The PAAm-Ferritin hybrid hydrogels present excellent biocompatibility and increased conductivity compared with PAAm hydrogel. Impressively, as a wearable flexible strain sensor, the PAAm-Ferritin hybrid hydrogels have high sensitivity (gauge factor = 2.06), excellent reliability, and cycling stability. This study indicates the feasibility of utilizing ferritin to synthesize functional materials, which is conducive to expanding the use of protein synthesis of materials technology and application fields.

“Smart” alginate hydrogels in biosensing, bioactuation and biocomputing: State-of-the-art and perspectives

In addressing the demand for biocompatible wearable, implantable and injectable biomedical devices, alginate hydrogels stand out as promising candidates. Alginate hydrogels have been used as matrix for immobilization of proteins, responsive polymers and nanomaterials that lead to a wide range of stimuli-responsive “smart” (bio)(nano)composite hydrogels. In this perspective, we analyzed the most recent applications of “smart” alginate composite hydrogels in biomedical applications, such as biosensing, drug delivery, wound healing and biocomputing. The design and key-responsive element of the composites were discussed as well as their practical application in biologically relevant conditions and in vivo. Finally, we provide our insights into the limitations, challenges and future directions of this exciting research field.

A Wearable Strain Sensor Based on Electroconductive Hydrogel Composites for Human Motion Detection

AbstractHydrogels are becoming the default platform for flexible electronic applications—specifically, strain sensors. But the simultaneous realization of compliance, robustness, and strain sensitivity required, using environmentally friendly materials, remains challenging. Here a series of poly(vinyl alcohol) (PVA)‐based biocomposite hydrogels, comprising variable quantities of nanocellulose and sodium alginate formed by freeze/thaw cycling, is reported. The results indicate that a hybrid hydrogel is prepared via the incorporation of conductive polypyrrole/bacterial nanocellulose composite material into the optimized PVA‐based hydrogel matrix (yield strength = 6.0 MPa, elastic modulus = 2.4 MPa, stretchability >384%). The resulting hybrid material exhibits remarkable toughness, nonlinear conformability, and piezoresistivity and demonstrates good strain sensitivity over a considerable range of deformation (<≈200% elongation, maximum gauge factor = 0.96). Moreover, the hybrid hydrogel is assembled into a wearable piezoresistive sensor capable of detecting large‐range human motion with high sensitivity, stability, and repeatability over a few repeated loading cycles. Thus, there is potential for the application of the conductive hybrid hydrogel in flexible electronics, such as wearable devices for health monitoring, soft robotics, and biomedical implants. Furthermore, the implementation of biocompatible polymers and renewable materials, amongst other green design principles, provides scope for the design of sustainable high performance materials.

“Green” biocomposite Poly (vinyl alcohol)/starch cryogels as new advanced tools for the cleaning of artifacts

HypothesisGels made from synthetic polymers have improved the cleaning of artifacts, but there is the strong need to elaborate new systems through an all-green approach, developing materials with higher eco-compatibility while retaining optimal efficacy. Rice starch (RS) is a renewable biopolymer with high potential for formulating sustainable gels from composites with synthetic polymers, but its interaction with the latter in composite structures is poorly understood. ExperimentsPoly (vinyl alcohol) (PVA) and RS were used to obtain biocomposite hydrogels through a robust and “green” freeze-thawing route. For the first time, extensive understanding of these composites was tackled by investigating their gel structure and rheological behavior. The cleaning effectiveness of the PVA/RS gels was assessed on soiled modern painting mock-ups, whose water-sensitiveness makes their cleaning too risky using traditional tools. FindingsThe composites behave as strong gels whose structure and viscoelastic response are controlled tuning the PVA/RS ratio. X-ray scattering and thermal analysis suggested the formation of hybrid PVA-RS links. Starch amylopectin likely acts as a porogen, while amylose forms hydrogen bonds with PVA. The gels adhere to rough paint layers and remove soil effectively without detectable residues. Overall, the PVA/RS composites are highly effective and provide a significant step forward in the formulation of eco-sustainable cleaning formulations.

Magnetoresponsive biocomposite hydrogels comprising gelatin and valine based magnetic ionic liquid surfactant as controlled release nanocarrier for drug delivery

A strategic nanoparticle-free approach towards construction of magnetoresponsive biocomposite hydrogels is presented.

Conductive biocomposite hydrogels with multiple biophysical cues regulate schwann cell behaviors.

Peripheral nerve injuries are serious clinical events, and surgical treatment has certain limitations. Conductive hydrogels are promising biomaterials for neural tissue engineering, as they can enhance the functionality of neurons and Schwann cells (SCs) by mimicking the biophysical and biochemical cues existing in the natural extracellular matrix. It remains unexplored, however, whether there is a connection between the effects of different cues, such as hydrogel elasticity and conductivity, on SC fate. In the present work, we fabricated a series of conductive biocomposite hydrogels with the combination of silk fibroin (SF) and graphene oxide (GO) nanosheets and demonstrated an approach to control hydrogel electrical conductivity, independent of matrix elasticity and polymer concentration. Our results indicated that the soft substrates play a more critical role in SC survival, proliferation, spreading, and gene expression of neurotrophic factors, while the increased conductivity may also be beneficial to SC functional behaviors. These findings may promote the understanding of cell-matrix interactions and provide new insights for the design of neural tissue engineering scaffolds.

Composite Nanocellulose Fibers-Based Hydrogels Loading Clindamycin HCl with Ca2+ and Citric Acid as Crosslinking Agents for Pharmaceutical Applications.

Biocomposite hydrogels based on nanocellulose fibers (CNFs), low methoxy pectin (LMP), and sodium alginate (SA) were fabricated via the chemical crosslinking technique. The selected CNFs-based hydrogels were loaded with clindamycin hydrochloride (CM), an effective antibiotic as a model drug. The properties of the selected CNFs-based hydrogels loaded CM were characterized. The results showed that CNFs-based hydrogels composed of CNFs/LMP/SA at 1:1:1 and 2:0.5:0.5 mass ratios exhibited high drug content, suitable gel content, and high maximum swelling degree. In vitro assessment of cell viability revealed that the CM-incorporated composite CNFs-based hydrogels using calcium ion and citric acid as crosslinking agents exhibited high cytocompatibility with human keratinocytes cells. In vitro drug release experiment showed the prolonged release of CM and the hydrogel which has a greater CNFs portion (C2P0.5A0.5/Ca + Ci/CM) demonstrated lower drug release than the hydrogel having a lesser CNFs portion (C1P1A1/Ca + Ci/CM). The proportion of hydrophilic materials which were low methoxy pectin and sodium alginate in the matrix system influences drug release. In conclusion, biocomposite CNFs-based hydrogels composed of CNFs/LMP/SA at 1:1:1 and 2:0.5:0.5 mass ratios, loading CM with calcium ion and citric acid as crosslinking agents were successfully developed for the first time, suggesting their potential for pharmaceutical applications, such as a drug delivery system for healing infected wounds.

Biocomposite Hydrogels for the Treatment of Bacterial Infections: Physicochemical Characterization and In Vitro Assessment.

Hydrogels based on natural and synthetic polymers and inorganic nanoparticles proved to be a viable strategy in the fight against some Gram-positive and Gram-negative bacteria. Additionally, numerous studies have demonstrated the advantages of using ZnO nanoparticles in medicine due to their high antibacterial efficacy and relatively low cost. Consequently, the purpose of our study was to incorporate ZnO nanoparticles into chitosan/poly (vinyl alcohol)-based hydrogels in order to obtain a biocomposite with antimicrobial properties. These biocomposite hydrogels, prepared by a double crosslinking (covalent and ionic) were characterized from a structural, morphological, swelling degree, and mechanical point of view. FTIR spectroscopy demonstrated both the apparition of new imine and acetal bonds due to covalent crosslinking and the presence of the sulfate group following ionic crosslinking. The morphology, swelling degree, and mechanical properties of the obtained hydrogels were influenced by both the degree of covalent crosslinking and the amount of ZnO nanoparticles incorporated. In vitro cytotoxicity assessment showed that hydrogels without ZnONPs are non-cytotoxic while the biocomposite hydrogels are weak (with 3% ZnONPs) or moderately (with 4 and 5% ZnONPs) cytotoxic. Compared to nanoparticle-free hydrogels, the biocomposite hydrogels show significant antimicrobial activity against S. aureus, E. coli, and K. pneumonia.

Removal of nafcillin sodium monohydrate from aqueous solution by hydrogels containing nanocellulose: An experimental and theoretical study

In the present work, new biocomposite hydrogels were prepared based on the vinyl monomer 2-methacroyloxyethyltrimethyl ammonium chloride (ClAETA) in the presence of nanofibrillated cellulose (CNF) for the removal of the emerging contaminant nafcillin sodium monohydrate (NFX). The hydrogels were synthesized via free radicals, with the amount of CNF varied, and characterized by fourier transform infrared spectroscopy (FT-IR), thermal gravimetric analysis (TGA), and scanning electron microscope (SEM) techniques. The capacity to absorb water and to remove NFX was determined through batch studies. It was observed that the presence of CNF significantly promotes both properties, with a hydration capacity of 2100% and an NFX adsorption capacity of 45 mg g−1 in P(ClAETA)1-12-2%CNF (pH 6, 0.01 g of adsorbent, initial concentration of NFX 200 mg g−1). The conformational study showed that in the most stable conformation, CNF avoids direct interaction with the NFX molecule. Herein, the main interactions are predominantly dominated by weak interactions such as London dispersion and electrostatic interactions between charged groups. Molecular dynamics simulations distinguish the existence of π-π stacking interactions between aromatic rings from NFX in the polymer + NFX system. Contact interactions were qualitatively and quantitatively characterized by the NCI index and the IGM analysis.

Supramolecular Biocomposite Hydrogels Formed by Cellulose and Host-Guest Polymers Assisted by Calcium Ion Complexes.

Hydrogels are biocompatible polymer networks; however, they have the disadvantage of having poor mechanical properties. Herein, the mechanical properties of host-guest hydrogels were increased by adding a filler and incorporating other noncovalent interactions. Cellulose was added as a filler to the hydrogels to afford a composite. Citric acid-modified cellulose (CAC) with many carboxyl groups was used instead of conventional cellulose. The preparation began with mixing an acrylamide-based αCD host polymer (p-αCD) and a dodecanoic acid guest polymer (p-AADA) to form supramolecular hydrogels (p-αCD/p-AADA). However, when CAC was directly added to p-αCD/p-AADA to form biocomposite hydrogels (p-αCD/p-AADA/CAC), it showed weaker mechanical properties than p-αCD/p-AADA itself. This was caused by the strong intramolecular hydrogen bonding (H-bonding) within the CAC, which prevented the CAC reinforcing p-αCD/p-AADA in p-αCD/p-AADA/CAC. Then, calcium chloride solution (CaCl2) was used to form calcium ion (Ca2+) complexes between the CAC and p-αCD/p-AADA. This approach successfully created supramolecular biocomposite hydrogels assisted by Ca2+ complexes (p-αCD/p-AADA/CAC/Ca2+) with improved mechanical properties relative to p-αCD/p-AADA hydrogels; the toughness was increased 6-fold, from 1 to 6 MJ/m3. The mechanical properties were improved because of the disruption of the intramolecular H-bonding within the CAC by Ca2+ and subsequent complex formation between the carboxyl groups of CAC and p-AADA. This mechanism is a new approach for improving the mechanical properties of hydrogels that can be broadly applied as biomaterials.