Glycol Chitosan Research Articles

Visible light-curable methacrylated glycol chitosan hydrogel patches for prenatal closure of fetal myelomeningocele

In this study, we prepared visible light-curable methacrylated glycol chitosan (MGC) hydrogel patches for the prenatal treatment of fetal myelomeningocele (MMC) and investigated their feasibility using a retinoic acid-induced fetal MMC rat model. 4, 5, and 6 w/v% of MGC were selected as candidate precursor solutions, and photo-cured for 20 s, because the resulting hydrogels were found to possess concentration dependent tunable mechanical properties and structural morphologies. Moreover, these materials exhibited no foreign body reactions with good adhesive properties in animal studies. The inflammation scoring assessment in vivo exhibited the absence of foreign body reactions in MGC hydrogel treated lesion. The complete epithelial coverage of MMC was made with using 6 w/v% MGC hydrogel followed by well-organized granulation along with noticeable decrease of abortion rate and wound size that highlight the therapeutic potential for the prenatal treatment of fetal MMC.

Intracellular Glucose-Depriving Polymer Micelles for Antiglycolytic Cancer Treatment.

A new anticancer strategy to exploit abnormal metabolism of cancer cells rather than to merely control the drug release or rearrange the tumor microenvironment is reported. An antiglycolytic amphiphilic polymer, designed considering the unique metabolism of cancer cells (Warburg effect) and aimed at the regulation of glucose metabolism, is synthesized through chemical conjugation between glycol chitosan (GC) and phenylboronic acid (PBA). GC-PBA derivatives form stable micellar structures under physiological conditions and respond to changes in glucose concentration. Once the micelles accumulate at the tumor site, intracellular glucose capture occurs, and the resultant energy deprivation through the inhibition of aerobic glycolysis remarkably suppresses tumor growth without significant side effects in vivo. This strategy highlights the need to develop safe and effective cancer treatment without the use of conventional anticancer drugs.

A robust high selectivity fluorescence turn-on nanoprobe for peroxynitrite detection in inflammatory cells and mice

Changed levels of intracellular peroxynitrite anion (ONOO−) are closely related to the occurrence and development of inflammation. Specific imaging of ONOO− at sites of inflammation can be of great significance not only for inflammation diagnosis but also for obtaining a deeper understanding of the role of ONOO− in inflammation. Therefore, there is an urgent need for constructing some reliable tools to study the relationship between ONOO− and inflammation in biosystems. In this work, we developed a robust high selectivity fluorescence turn-on nanoprobe (Rhb-ONOO) for inflammation-targeted imaging of ONOO−. The Rhb-ONOO was obtained by self-assembly of amphiphilic Rhb-ONOO, which was constructed by the condensation reaction of the hydrophobic, ONOO−-response and deep red-emitting fluorophore (Rhb) with hydrophilic biopolymer glycol chitosan (GC). Rhb-ONOO showed rapid response towards ONOO− during 60 s, high sensitivity with 19-fold enhancement of fluorescence intensity ratio (I628/I0), and excellent selectivity towards ONOO− over other analytes as well as a good linear relationship was observed between the I628/I0 and the ONOO− concentration range 0–1 μM, with an excellent limit of detection (LOD) of 33 nM. Impressively, it was successfully employed Rhb-ONOO for ONOO− imaging in living inflammatory cells and drug-induced inflammatory mice, illustrating nanoprobe Rhb-ONOO has excellent potential for further study ONOO−-related inflammatory diseases.

‘Priming’ protects Piper nigrum L. from Phytophthora capsici through reinforcement of phenylpropanoid pathway and possible enhancement of Piperine biosynthesis

Piper nigrum L. (black pepper), a woody perennial spice crop indigenous to India is positioned at the phylogenetically unique basal lineage of angiosperms. Cultivation of this major spice crop is constrained by rampant fungal and viral infections leading to a lack of disease-free planting material. The major disease that poses severe threat to P. nigrum plantations and nurseries is ‘quick wilt’ caused by the oomycete Phytophthora capsici, which affects the leaf, stem, spike, collar and root. In this paper, we report the consequence of priming in modulating Piper nigrum defense against Phytophthora capsici. Glycol Chitosan (GC) was used to infiltrate detached leaves of mature P. nigrum plants. It was observed that pre-treatment of GC for 24 hours resulted in significant reduction of disease symptoms in infected leaves, as evidenced by the marked decrease in the size of lesions, and also delayed the appearance of symptoms up to 72 hpi. Experiments repeated in P. nigrum seedlings under controlled growth conditions indicate that delayed disease symptoms of GC pre-treated leaves do not spread to healthy uninfiltrated leaves suggesting a priming-associated systemic defense response. An ROS-mediated manifestation of Hypersensitive Response (HR) induced by Chitosan was also evident in pre-treated leaves. A corresponding visual indication of increased lignification was observed, which correlated with an enhanced lignin content of GC-treated leaves. Enhanced callose deposition was also apparent in GC infiltrated leaves, establishing a stimulatory effect of GC in triggering HR through ROS production, enhanced lignification and callose deposition. Key genes of the core phenylpropanoid and isoprenoid pathways along with major defense signalling pathway genes of P. nigrum, including pathogenesis-related genes and hormone signalling genes showed significant transcript enrichment consequential to GC treatment. A significant quantitative enhancement in Piperine content was evident in GC-infiltrated leaves. The systemic nature of priming on disease protection was established through experiments conducted in rooted cuttings monitored for 30 days after disease infection. This is the first report that provides strong molecular evidence endorsing the twofold advantage of defense priming in P. nigrum by improving crop protection with a concomitant enhancement in Piperine biosynthesis.

A Movable Drug Carrier with High Affinity to Bacteria for Precise Antibacterial Therapy

AbstractPathogenic bacteria infection, which is an extremely serious clinical problem, could be effectively treated by the antibiotics, but the misuse of antibiotics caused by imprecise transportation is a huge problem that causes the emergence of multidrug‐resistant bacteria, which can kill millions of people. Herein, a drug‐carrier is developed that can deliver antibiotics precisely to the bacteria and kill bacteria efficiently, thus avoiding the misuse of antibiotics. These drug carriers, consisting of ciprofloxacin (cip)‐loaded CaCO3 coated by asymmetrical glycol chitosan (GCS) (cip‐loaded CaCO3@GCS carriers, abbreviated as CC@GCs), could move autonomously in the acidic environment caused by the bacteria‐infection, which is based on the asymmetric pressure generated by the CO2 concentration gradient due to the asymmetric reaction between CaCO3 and acid. The motion of CC@GCs increases its probability to contact the bacteria, leading to the formation of effective electrostatic binding between them. The combination of movement and enhanced affinity to bacteria enable CC@GCs to precisely deliver drug to bacteria and kill them more efficiently as compared to the free drug, which shows effective treatment in bacterial infection abscess on skin with improved drug utilization. The CC@GCs based drug carriers have great potentials in treating bacterial infection with precision for efficient antibacterial therapy and alleviating the antibiotic misusage.

Prediction the clinical EPR effect of nanoparticles in patient-derived xenograft models.

Many preclinically tested nanoparticles in existing animal models fail to be directly translated into clinical applications because of their poor resemblance to human cancer. Herein, the enhanced permeation and retention (EPR) effect of glycol chitosan nanoparticles (CNPs) in different tumor microenvironments (TMEs) was compared using different pancreatic tumor models, including pancreatic cancer cell line (BxPC3), patient-derived cancer cell (PDC), and patient-derived xenograft (PDX) models. CNPs were intravenously injected into different tumor models, and their accumulation efficiency was evaluated using non-invasive near-infrared fluorescence (NIRF) imaging. In particular, differences in angiogenic vessel density, collagen matrix, and hyaluronic acid content in tumor tissues of the BxPC3, PDC, and PDX models greatly affected the tumor-targeting efficiency of CNPs. In addition, different PDX models were established using different tumor tissues of patients to predict the clinical EPR effect of CNPs in inter-patient TMEs, wherein the gene expression levels of PECAM1, COL4A1, and HAS1 in human tumor tissues were observed to be closely related to the EPR effect of CNPs in PDX models. The results suggested that the PDX models could mimic inter-patient TMEs with different blood vessel structures and extracellular matrix (ECM) content that critically affect the tumor-targeting ability of CNPs in different pancreatic PDX models. This study provides a better understanding of the heterogeneity and complexity of inter-patient TMEs that can predict the response of various nanoparticles in individual tumors for personalized cancer therapy.

Increased susceptibility to doxorubicin-induced cell death in acute lymphocytic leukemia cells by inhibiting serine/threonine WEE1 kinase expression using the chitosan-carboxymethyl dextran-polyethylene glycol-TAT nanoparticles

Prevention of drug resistance is a significant challenge in treating Acute Lymphoblastic Leukemia. It has been demonstrated that activating DNA Damage Repair (DDR) pathways play an essential role in resistance mechanisms. WEE1 serine/threonine kinase overexpression is crucial for activating DDR pathways in normal and cancerous cells due to the treatment by DNA-damage-based chemotherapeutic agents such as doxorubicin (Dox). In this study, for the first time, TAT-conjugated polyethylene glycol chitosan Carboxymethyl Dextran (TAT-PEG-CCMD) nanoparticles (NPs) were used to deliver anti-WEE1 siRNA and Dox to ALL cells to inhibit WEE1 kinase overexpression to overcome drug-resistance. The results showed that TAT-PEG-CCMD NPs could efficiently deliver WEE1 kinase siRNA and Dox to ALL cell lines (Jurkat and NALM6) and ALL primary cells (peripheral blood and bone marrow mononuclear cells) isolated from patients with ALL. Transfection of leukemic cells led to silencing WEE1 in target cells. Interestingly, silencing of WEE1 in ALL cell lines and ALL primary cells significantly enhanced the apoptotic effects of Dox. These findings imply that combination therapy of ALL using TAT-PEG-CCMD NPs loaded with anti-WEE1 siRNA and Dox can be considered a novel anti-cancer therapeutic approach that should be further investigated in future studies.

All-trans Retinoic Acid-incorporated Glycol Chitosan Nanoparticles Regulate Macrophage Polarization in Pg-LPS-Induced Inflammation.

The occurrence and development of inflammation are closely correlated to the polarization of macrophages. All-trans retinoic acid (ATRA) has been proven to promote the polarization of macrophages from M1 to M2, but this lacks an effective carrier to participate in the biological response. The present study aims to determine whether retinoic acid-incorporated glycol chitosan (RA-GC) nanoparticles can regulate macrophage polarization in Porphyromonas gingivalis-lipopolysaccharide (Pg-LPS)-induced inflammation. Mouse 264.7 cell lines were treated with 1 µg/mL Pg-LPS to induce inflammation. After the effects of ATRA and RA-GC on the activity of macrophages were detected by CCK-8 assay, cells induced with Pg-LPS were assigned to the blank control group (GC) nanoparticles without ATRA, and experimental groups (GC nanoparticles loaded with different concentrations of ATRA: 1, 10 and 100 µg/mL). The effects of RA-GC on inflammatory cytokines tumor necrosis factor-α, interleukin (IL)-10 and IL-12 in macrophages were detected by enzyme-linked immunosorbent assay (ELISA). Subsequently, the effects of GC nanoparticles loaded with/without ATRA on macrophage polarization in an inflammatory environment were detected by RT-PCR and Western blotting. The results revealed that RA-GC had no significant effect on macrophage activity. However, RA-GC could effectively inhibit the Pg-LPS-induced inflammatory factor expression in macrophages. Meanwhile, the experimental results confirmed that RA-GC could downregulate the expression of inducible nitric oxide synthase (iNOS) (a marker of M1 macrophages) and upregulate the expression of mannose receptor and Arginase-1 (a marker of M2 macrophages) in a dose-dependent manner. The present study confirms that RA-GC can promote the M2 polarization of macrophages in an inflammatory environment, and proposes this as a promising target for the clinical treatment of Pg-LPS-related diseases.

Safety assessment of different unloaded polymeric nanocapsules in Caenorhabditis elegans

Nano-sized drug delivery systems have been the subject of intense research in recent years because polymeric materials allow the absorption and release of active substances in a controlled manner. Despite the benefits, the safety of nanoparticulate systems is an aspect to be understood, particularly in vivo systems. Caenorhabditis elegans is a very useful alternative model for nanotoxicology and has been recently applied in this field. The aim of this study was to evaluate toxicological endpoints in C. elegans exposed to nanocapsules (NC) prepared with different coatings: polysorbate 80 (NCP80); polyethylene glycol (NCPEG), Eudragit® RS 100 (NCEUD) and chitosan (NCCS). Nanocapsules were prepared by nanoprecipitation method and showed acceptable physico-chemical characterization. Polyethylene glycol nanocapsules and chitosan nanocapsules increased worms lethality in a dose-dependent manner in acute exposure; polysorbate 80 nanocapsules, polyethylene glycol nanocpsules and chitonan nanocapsules also increased lethality following chronic exposure. Chitosan nanocapsules were the most toxic in all exposures, demonstrating toxicity even at low concentrations. Reproduction and body length were not affected by any of the nanocapsules exposures. The expression of superoxide dismutase showed that polysorbate 80 nanocapsules at the highest concentration slightly increased SOD-3::GFP expression. On the other hand, chitosan nanocapsules exposure blunted SOD-3 expression. This work demonstrates the toxicological differences between nanocapsule produced with different coatings and indicates higher safety for the use of eugragit nanocapsule in new formulations for future drug delivery and targeting systems.

PH-Sensitive Twin Liposomes Containing Quercetin and Laccase for Tumor Therapy.

In this study, functional twin liposomes (TLs) were designed by linking avidin-anchored single liposomes and biotin-anchored single liposomes via avidin-biotin interactions. Here, we first punched a hole on the liposome surface using the liposome magnetoporation method to prepare functional single liposomes, which were used for safely encapsulating quercetin (QER, as a model prodrug) or laccase (LAC, as a bioactive enzyme) inside the liposomes without the use of organic solvents; the pores were then plugged by pH-sensitive glycol chitosan grafted with 3-diethylaminopropylamine (GDEAP) and avidin (or biotin). As a result, single liposomes with QER and biotin-GDEAP were efficiently coupled with other liposomes with LAC and avidin-GDEAP. We demonstrated that the TLs could accelerate QER and LAC release at acidic pH (6.8), improving the LAC-mediated oxidization of QER and significantly elevating tumor cell death, suggesting that this strategy can be used as an efficient method for the programmed action of prodrugs.

Stretchable and Fast Composting Polyester Films with High-Performance Oxygen Barrier

This work presents one of the fastest composting aliphatic–aromatic polyesters with a good balance of mechanical and barrier properties, making it a sustainable alternative for low-density polyethylene in packaging. The polyesters (PBxBDMyS) are prepared by melt polycondensation of 1,4-butanediol (B), 1,4-benzenedimethanol (BDM), and succinic acid (S). One composition exhibited a tensile strength of 20 ± 2 MPa, a modulus of 150 ± 8 MPa, and a very high elongation at break of 581 ± 46%. The low oxygen transmission rate (152 cm3·m–2·day–1·bar–1) measured at 65% relative humidity and 23 °C confirms excellent barrier performance. A 3 μm water-borne nanocomposite coating of glycol chitosan and sodium fluorohectorite further reduced the gas permeability to a value of 0.75 cm3·m–2·day–1·atm–1, which is competitive with materials suitable for demanding packaging applications such as poly(vinylidene chloride) while maintaining good mechanical properties and high stretchability. After studying the enzyme-catalyzed hydrolysis under controlled conditions, the full fragmentation, assimilation, and mineralization in thermophilic, aerobic composting could be confirmed in less than 5 weeks using a combination of different analytical methods. The mechanism of degradation was proven to be bulk degradation.

The impact of varying dextran oxidation levels on the inhibitory activity of a bacteriocin loaded injectable hydrogel

In the design of injectable antimicrobial dextran-alginate hydrogels, the impact of dextran oxidation and its subsequent changes in molecular weight and the incorporation of glycol chitosan on (i) gel mechanical strength and (ii) the inhibitory profile of an encapsulated bacteriocin, nisin A, are explored. As the degree of oxidation increases, the weight average molecular mass of the dextran decreases, resulting in a reduction in elastic modulus of the gels made. Upon encapsulation of the bacteriocin nisin into the gels, varying the dextran mass/oxidation level allowed the antimicrobial activity against S. aureus to be controlled. Gels made with a higher molecular weight (less oxidised) dextran show a higher initial degree of inhibition while those made with a lower molecular weight (more oxidised) dextran exhibit a more sustained inhibition. Incorporating glycol chitosan into gels composed of dextran with higher masses significantly increased their storage modulus and the gels’ initial degree of inhibition.Graphical abstract

Synthesis of Polyethylene Glycol–Chitosan–Nano Ag Composites and their Antibacterial Properties

Synthesis of Polyethylene Glycol–Chitosan–Nano Ag Composites and their Antibacterial Properties

Antifungal Activity and Properties of Crude Enzymes Produced from Cellulomonas fimi JH-1

In this study, bacteria were isolated from rosemary rhizosphere and chitinolytic activity was detected in 0.2% chitin agar medium. Using 16s rRNA sequencing, the isolated bacteria were identified as Cellulomonas fimi. Chitinase, cellulase, and protease activities were found to increase with incubation time. Chitosanase activity was highest on day 1, and gradually declined thereafter. Crude enzyme of C. fimi was prepared and separated by SDS-PAGE and the expression patterns of enzyme activity for chitinase and chitosanase isozymes was studied. Three chitinase isozymes (36, 55, and 66 kDa) and one chitosanase (39 kDa) were detected SDS-PAGE gel combinded with glycol chitin and glycol chitosan, and these chitinase and chitosanase had different molecular weights. Indole acetic acid (IAA) production by C. fimi was analyzed in nutrient broth (NB) media containing different concentrations of tryptophan. IAA production was found to increase with increasing tryptophan concentration. Siderophore production by C. fimi was analyzed in colloidal chitin medium for 0, 1, 3, 5, and 7 d. The production of siderophore increased for 5 d and gradually decreased thereafter. The antifungal activities of C. fimi against G. zeae, F. solani, B. cinerea, F. oxysporum, C. cucumerinum, R. solani, and C. acutatum were investigated in potato dextrose broth medium containing chitin. C. fimi showed the highest antifungal activity against G. zeae.

Glycol-Chitosan-Based Technetium-99m-Loaded Multifunctional Nanomicelles: Synthesis, Evaluation, and In Vivo Biodistribution.

We hereby propose the use of stable, biocompatible, and uniformly sized polymeric micelles as high-radiotracer-payload carriers at region-of-interest with negligible background activity due to no or low offsite radiolysis. We modified glycol chitosan (GC) polymer with varying levels of palmitoylation (P) and quaternization (Q). Quaternary ammonium palmitoyl glycol chitosan (GCPQ) with a Q:P ratio of 9:35 (Q9P35GC) offers >99% biocompatibility at 10 mg mL−1. Q9P35GC micelles exhibit >99% 99mTechnetium (99mTc) radiolabeling via the stannous chloride reduction method without heat. The 99mTc-Q9P35GC micelles (65 ± 3 nm) exhibit >98% 6 h serum stability at 37 °C and 7 day of radiochemical stability at 25 °C. HepG2 cells show a higher uptake of FITC-Q9P35GC than Q13P15GC and Q20P15GC. The in vivo 24 h organ cumulated activity (MBq h) order follows: liver (234.4) > kidneys (60.95) > GIT (0.73) > spleen (88.84). The liver to organ ratio remains higher than 2.4, rendering a better contrast in the liver. The radiotracer uptake decreases significantly in fibrotic vs. normal liver, whereas a blocking study with excess Q9P35GC significantly decreases the radiotracer uptake in a healthy vs. fibrotic liver. FITC-Q9P35GC shows in vivo hepato-specific uptake. Radiotracer liver uptake profile follows reversible binding kinetics with data fitting to two-tissue compartmental (2T), and graphical Ichise multilinear analysis (MA2) with lower AIC and higher R2 values, respectively. The study concludes that 99mTc-Q9P35GC can be a robust radiotracer for noninvasive hepatocyte function assessment and diagnosis of liver fibrosis. Furthermore, its multifunctional properties enable it to be a promising platform for nanotheranostic applications.

Strong and Elastic Hydrogels from Dual-Crosslinked Composites Composed of Glycol Chitosan and Amino-Functionalized Bioactive Glass Nanoparticles.

Mesoporous bioactive glass (BG) nanoparticles (NPs) with a high specific surface area were prepared. The surfaces of BG NPs were further modified using an amino-containing compound or synthesized precursors to produce three kinds of amino-functionalized bioactive glass (ABG) NPs via devised synthetic routes. The achieved ABG NPs possessed various spacer lengths with free amino groups anchored at the end of the spacer. These ABG NPs were then combined with glycol chitosan (GCH) to construct single- or dual-crosslinked ABG/GCH composite hydrogels using genipin (GN) alone as a single crosslinker or a combination of GN and poly(ethylene glycol) diglycidyl ether (PEGDE) as dual crosslinkers. The spacer length of ABG NPs was found to impose significant effects on the strength and elasticity of GN-crosslinked ABG/GCH hydrogels. After being dually crosslinked with GN and PEGDE, the elastic modulus of some dual-crosslinked ABG/GCH hydrogels reached around 6.9 kPa or higher with their yielding strains larger than 60%, indicative of their strong and elastic features. The optimally achieved ABG/GCH hydrogels were injectable with tunable gelation time, and also able to support the growth of seeded MC3T3-E1 cells and specific matrix deposition. These results suggest that the dual-crosslinked ABG/GCH hydrogels have the potential for some applications in tissue engineering.

Glycol chitosan stabilized bimolecular nanoparticles for chemo photothermal killing of breast cancer cells

We report a bi-molecular combination nanomedicine consisting of IR820 dye and chemotherapeutic drug lapatinib stabilized with the polyelectrolyte, glycol chitosan. The synthesized nanoformulation revealed superior photothermal transduction efficiency due to strong NIR (Near Infrared) absorbance of IR820. The in-vitro studies showed the time-dependent increase in cellular uptake of nanoparticles with significant photothermal chemotherapeutic toxicity against cancer cells. Moreover, acute toxicity assessment in Balb/c mice showed no systemic dysfunction of vital organs post intravenous injection of IR/LNPs.

Gene Targeting to the Cerebral Cortex Following Intranasal Administration of Polyplexes.

Gene delivery to the cerebral cortex is challenging due to the blood brain barrier and the labile and macromolecular nature of DNA. Here we report gene delivery to the cortex using a glycol chitosan—DNA polyplex (GCP). In vitro, GCPs carrying a reporter plasmid DNA showed approximately 60% of the transfection efficiency shown by Lipofectamine lipoplexes (LX) in the U87 glioma cell line. Aiming to maximise penetration through the brain extracellular space, GCPs were coated with hyaluronidase (HYD) to form hyaluronidase-coated polyplexes (GCPH). The GCPH formulation retained approximately 50% of the in vitro hyaluronic acid (HA) digestion potential but lost its transfection potential in two-dimensional U87 cell lines. However, intranasally administered GCPH (0.067 mg kg−1 DNA) showed high levels of gene expression (IVIS imaging of protein expression) in the brain regions. In a separate experiment, involving GCP, LX and naked DNA, the intranasal administration of the GCP formulation (0.2 mg kg−1 DNA) resulted in protein expression predominantly in the cerebral cortex, while a similar dose of intranasal naked DNA led to protein expression in the cerebellum. Intranasal LX formulations did not show any evidence of protein expression. GCPs may provide a means to target protein expression to the cerebral cortex via the intranasal route.

Application of Hexanoyl Glycol Chitosan as a Non-cell Adhesive Polymer in Three-Dimensional Cell Culture

Cell culture technology has evolved into three-dimensional (3D) artificial tissue models for better reproduction of human native tissues. However, there are some unresolved limitations that arise due to the adhesive properties of cells. In this study, we developed a hexanoyl glycol chitosan (HGC) as a non-cell adhesive polymer for scaffold-based and -free 3D culture. The uniform cell distribution in a porous scaffold was well maintained during the long culutre period on the HGC-coated substrate by preventing ectopic adhesion and migration of cells on the substrate. In addition, when culturing many spheroids in one dish, supplementation of the culture medium with HGC prevented the aggregation of spheroids and maintained the shape and size of spheroids for a long culture duration. Collectively, the use of HGC in 3D culture systems is expected to contribute greatly to creating excellent regenerative therapeutics and screening models of bioproducts.

Janus Nanoparticle Coupled Double‐Network Hydrogel

For double network (DN) hydrogels, their performance can be tuned by adjusting the interaction between their two networks. A novel DN hydrogel toughening approach is proposed by employing Janus nanoparticles (JNs) as crosslinkers to gain a conjoined-network hydrogel. First, a kind of JNs modified by amino groups and quaternary ammonium salt is synthesized, named R3 N+ -JN-NH2 . The DN hydrogel is fabricated based on ionic coordination between calcium chloride (CaCl2 ) and sodium alginate (Alg), as well as covalent (benzoic imine) between glycol chitosan (GC) and benzaldehyde-capped poly(ethylene oxide) (BzCHO-PEO-BzCHO). Based on the same covalent and ionic dynamic crosslinking mechanism, the added R3 N+ -JN-NH2 interacts with two networks to promote crosslinking to form a dually crosslinked structure. The R3 N+ -JN-NH2 effectively provides more energy dissipation, and the hydrogel with conjoined networks shows better compression resistance.