Preparation of antibacterial hydrogel from poly(aspartic hydrazide) and quaternized N-[3-(dimethylamino) propyl] methylacrylamide copolymer with antioxidant and hemostatic effects for wound repairing.

Hydrogels as wound dressing have attracted extensive attention in past decade because they can provide moist microenvironment to promote wound healing. Herein, this research designed a multifunctional hydrogel with antibacterial property and antioxidant activity fabricated from quaternary ammonium bearing light emitting quaternized TPE-P(DAA-co-DMAPMA) (QTPDD) and poly(aspartic hydrazide) (PAH). The protocatechuic aldehyde (PCA) grafted to the hydrogel through dynamic bond endowed the hydrogel with antioxidant activity and the tranexamic acid (TXA) was loaded to enhance the hemostatic performance. The hydrogel possesses preferable gelation time for injectable application, good antioxidant property and tissue adhesion, improved hemostatic performance fit for wound repairing. Furthermore, the hydrogel has excellent antimicrobial property to both E. coli and S. aureus based on quaternary ammonium structure. The hydrogel also showed good biocompatibility and the in vivo experiments proved this hydrogel can promote the wound repairing rate. This study suggests that TXA/hydrogel with quaternary ammonium structure and dynamic grafted PCA have great potential in wound healing applications.

Matairesinoside, a novel inhibitor of TMEM16A ion channel, loaded with functional hydrogel for lung cancer treatment.

The incidence and mortality rates of lung cancer have remained high for several decades, necessitating the discovery of new drugs and the development of effective treatment strategies. This study identified matairesinoside (MTS) as a potent inhibitor of TMEM16A, a novel drug target for lung cancer. Molecular simulation combined with site-directed mutagenesis experiments confirmed the key binding sites of MTS and TMEM16A. Cell experiments demonstrated that MTS significantly inhibited the growth, migration, and invasion of lung cancer cells, while inducing apoptosis. Gene knockdown and overexpression studies further revealed that TMEM16A is the target for MTS in regulating lung cancer cell growth. Western blot analysis elucidated the signaling transduction network involved in MTS-mediated regulation of lung cancer. Building upon these findings, a biodegradable self-healing functional hydrogel was developed to load MTS, aiming to enhance therapeutic efficacy and minimize side effects in vivo. Animal experiments demonstrated that the hydrogel/MTS formulation exhibited satisfactory inhibitory effects on lung cancer and mitigated the side effects associated with direct MTS injection. This study identified MTS as a potential candidate for anti-lung cancer therapy with well-defined pharmacological mechanisms. Moreover, the targeted drug delivery system utilizing the hydrogel/MTS platform offers a promising approach for lung cancer treatment.

Enhanced protective efficacy of an OprF/PcrV bivalent DNA vaccine against Pseudomonas aeruginosa using a hydrogel delivery system.

Pseudomonas aeruginosa (PA) is one of the leading pathogens responsible for hospital-acquired infections. With the increasing antibiotic resistance of PA, clinical treatment has become increasingly challenging. DNA vaccines represent a promising approach for combating PA infection. However, the immune response induced by a single antigen is limited, and combination vaccines hold greater therapeutic potential. The highly conserved OprF and PcrV genes are attractive candidate antigens for vaccine development, but the poor delivery of such vaccines has limited their clinical application. In this study, we constructed an OprF/PcrV bivalent DNA vaccine, and a polyaspartamide/polyethylene glycol di-aldehyde (PSIH/PEG DA) hydrogel was formulated to improve DNA delivery. The OprF/PcrV DNA vaccine formulated with the PSIH/PEG DA hydrogel was carefully characterized in vitro and in vivo and showed suitable compatibility. The PSIH/PEG DA hydrogel formulation induced a mixed Th1/Th2/Th17 immune response in mice, leading to a significant increase in antibody titers, lymphocyte proliferation rates, and cytokine levels compared to those in mice treated with single or combined vaccines. The PSIH/PEG DA hydrogel delivery system significantly enhanced the immune protection of the DNA vaccine in a murine pneumonia model, as revealed by the reduced bacterial burden and inflammation in the mouse lungs and increased survival rate. In conclusion, the PSIH/PEG DA hydrogel delivery system can further enhance the immune efficacy of the combination OprF/PcrV DNA vaccine. This research provides a novel optimized strategy for the prevention and treatment of PA infection using DNA vaccines.

Pectin based hydrogel with covalent coupled doxorubicin and limonin loading for lung tumor therapy.

Self-healing hydrogels have shown great application potential in drug delivery for anti-tumor therapy and tissue engineering. In this research, Doxorubicin (DOX) was coupled onto the oxidized pectin (pec-Ald) to prepare DOX grafted pec-AD and used to fabricate self-healing hydrogel for lung cancer therapy combined with novel herbal medicine extract limonin targeting lung cancer cells. The hydrogel was prepared with P(NIPAM195-co-AH54) cross-linking and the hydrazone bond cross-linked hydrogel showed good mechanical property and self-healing behavior. With pectin composition, the hydrogel was still biodegradable catalyzed by enzyme and in vivo. The hydrogel formed fast fit for injectable application and the hydrogel itself showed moderate lung cancer inhibition activity. With limonin loading, the hydrogel showed synergistic lung cancer therapy with the tumor growth greatly inhibited. The covalent coupling of DOX and loaded limonin in the hydrogel decreased in vivo toxicity and the hydrogel degraded on time. With biodegradability and improved lung cancer therapy efficiency, this DOX grafted self-healing hydrogel could find great potential application in cancer therapy in near future.

Pectin-based double network hydrogels as local depots of celastrol for enhanced antitumor therapy.

In this study, A double-network (DN) hydrogel composed of a physical glycyrrhizic acid (GA) network and a chemically crosslinked pectin-based network was fabricated as a local depot of celastrol (CEL) for cancer treatment. The obtained DN hydrogel possessed excellent mechanical performance, flexibility, biocompatibility, biodegradability and self-healing property. Furthermore, the release profile of CEL loaded DN hydrogel maintained a controlled and sustained release of CEL for a prolonged period. Finally, in vivo animal experiments demonstrated that the DN hydrogel could significantly enhance the therapeutic efficiency of CEL in CT-26 tumor-bearing mice upon intratumoral injection while effectively alleviate the toxicity of the CEL. In summary, this injectable pectin-based double network hydrogels are ideal delivery vehicle for tumor therapy.

Bioinspired poly(aspartic acid) based hydrogel with ROS scavenging ability as mEGF carrier for wound repairing applications.

Poly(amino acid) based self-healing hydrogels have important application in biomedications. In this research, the catechol pendant groups were imported to poly(aspartic acid) based self-healing hydrogel to improved skin adhesion and ROS scavenging performance. The poly(succinimide) (PSI) was reacted with 3,4-dihydroxyphenylalanine (DA) and then hydraziolyzed to import catechol group and hydrazide group respectively, which are responsible for mussel inspired tissue adhesion and dynamic coupling reactivity. The dopamine modified poly(aspartic hydrazide) (PDAH) was reacted with PEO90 dialdehyde (PEO90 DA) to prepare hydrogels, and the resultant hydrogel showed good biocompatibility both in vitro and in vivo. The skin adhesion strength of the mussel inspired hydrogel increased notably with enhanced radical scavenging efficiency fit for in vivo wound repairing applications. The PDAH/PEO90 DA hydrogel also showed sustained albumin release profile and the in vivo wound repairing experiment proved the mouse Epidermal Growth Factor (mEGF) loaded hydrogel as wound dressing material accelerated the wound repairing rate.

Mussel-inspired self-healing hydrogel form pectin and cellulose for hemostasis and diabetic wound repairing.

Diabetic wound is considered as a kind of chronic wound prone to infection and difficult to repair due to high glucose level in the blood of patients. In this research, a biodegradable self-healing hydrogel with mussel inspired bioadhesion and anti-oxidation properties is fabricated based on Schiff-base cross-linking. The hydrogel was designed from dopamine coupled pectin hydrazide (Pec-DH) and oxidized carboxymethyl cellulose (DCMC) for mEGF loading as a diabetic wound repair dressing. The Pectin and CMC as natural feedstock endowed the hydrogel with biodegradability to avoid possible side effects, while the coupled catechol structure could enhance the tissue adhesion of the hydrogel for hemostasis. The results showed the Pec-DH/DCMC hydrogel formed fast and can cover irregular wounds with good sealing effect. The catechol structure also improved the reactive oxygen species (ROS) scavenging ability of the hydrogel, which can eliminate the negative effect of ROS during wound healing. The in vivo diabetic wound healing experiment revealed the hydrogel as mEGF loading vehicle greatly enhanced the diabetic wound repairing rate in mice model. As a result, the Pec-DH/DCMC hydrogel could show advantages as EGF carrier in wound healing applications.

Carboxymethylcellulose based self-healing hydrogel with coupled DOX as Camptothecin loading carrier for synergetic colon cancer treatment.

The self-healing hydrogels have important applications in biomedication as drug release carrier. In this research, the Doxorubicin (DOX) was coupled onto oxidized carboxymethylcellulose (CMC) (CMC-Ald) to fabricate self-healing hydrogel with intrinsic antitumor property and loaded with Camptothecin (CPT) for synergetic antitumor treatment. The DOX coupled CMC-Ald (CMC-AD) was reacted with poly(aspartic hydrazide) (PAH) to fabricate injectable self-healing hydrogel. The coupled DOX avoided the burst release of the drug and the 100 % CPT loaded hydrogel could take the advantages of both drugs to enhance the synergetic antitumor therapeutic effect. The in vitro and in vivo results revealed the CPT loaded CMC-AD/PAH hydrogel showed enhanced antitumor property and reduced biotoxicity of the drugs. These properties demonstrate that the CMC-AD/PAH hydrogel has great application prospects in biomedication.

Biodegradable hydrogel from pectin and carboxymethyl cellulose with Silibinin loading for lung tumor therapy.

Serious side effects of chemotherapy drugs greatly limited the anticancer performance, while targeted drug delivery could improve the therapeutic effect and reduce side effects. In this work, biodegradable hydrogel was fabricated from pectin hydrazide (pec-H) and oxidized carboxymethyl cellulose (DCMC) for localized Silibinin delivery in lung adenocarcinoma treatment. The self-healing pec-H/DCMC hydrogel showed blood compatibility and cell compatibility both in vitro and in vivo, and could be degraded by enzymes. The hydrogel also formed fast fit for injectable applications and showed sustained drug release characteristic sensitive to pH based on acylhydrzone bond cross-linked networks. The Silibinin, as a specific lung cancer inhibiting drug targets TMEM16A ion channel, was loaded into the pec-H/DCMC hydrogel to treat the lung cancer in mice model. The results showed that the hydrogel loaded Silibinin significantly enhanced the anti-tumor efficiency in vivo and greatly reduced the toxicity of the Silibinin. Based on the dual effect of improving efficacy and reducing side effects, the pec-H/DCMC hydrogel with Silibinin loading have broad application prospects to inhibit lung tumor growth in clinic.

Cellulose based self-healing hydrogel through Boronic Ester connections for wound healing and antitumor applications.

The application of biodegradable hydrogels in medical field has drawn great attention because their networked structure provided ideal spaces for drug loading and cell growth. In this research, the boronic acid was coupled onto carboxyethyl cellulose (CMC) to synthesize boronic acid grafted CMC (CMC-BA) conveniently and self-healing hydrogel was fabricated with polyvinyl alcohol (PVA) crosslinking through dynamic boronic ester bond. The CMC-BA/PVA hydrogel showed good biocompatibility and could be degraded by cellulase and in vivo. The hydrogel formed fast fit for localized injection to cover the irregular wounds and localize the antitumor drugs to the tumor site. The in vivo wound repairing experiment revealed the hydrogel could form airtight adhesion to the wound site to reduce blood loss and accelerate the wound repairing rate. The hydrogel as a drug release carrier also reduced the acute in vivo toxicity of DOX with antitumor performance well preserved through a controlled release profile. Based on the above advantages, the CMC-based hydrogel with boronic ester connection should have great potential in biomedical areas with profitable future.

Self-healing pectin/cellulose hydrogel loaded with limonin as TMEM16A inhibitor for lung adenocarcinoma treatment.

Lung cancer as one of the highest incident malignant tumors did not receive satisfactory chemotherapy due to lack of specific drug targets and targeted drugs. This study screened a new effective lung tumor inhibitor limonin from herbal medicine, which inhibited proliferation and promoted apoptosis of lung adenocarcinoma cells by targeting specific high expressed TMEM16A ion channel. Moreover, a novel biodegradable self-healing hydrogel was prepared from acylhydrazide functionalized carboxymethyl cellulose (CMC-AH) and oxidized pectin (pec-CHO) to reduce the side effects of the limonin to the body. The hydrogels showed fast gelation, good biocompatibility and sustained limonin release property. The limonin-loaded hydrogel significantly inhibited the growth of lung adenocarcinoma in xenografts mice because the limonin inhibited the proliferation, migration and promoted apoptosis of LA795 cells, and eliminated the acute toxicity through sustained release from the hydrogel. Combined the antitumor performance of the limonin and sustained release of pec-CHO/CMC-AH hydrogel, this limonin/hydrogel system achieved satisfactory antitumor effect and eliminated side effects in vivo. Therefore, this system has great potential application for enhanced lung adenocarcinoma therapy.

Cellulose-based thermo-responsive hydrogel with NIR photothermal enhanced DOX released property for anti-tumor chemotherapy.

Thermo-sensitive hydrogels change their properties through phase transition, which could be used to regulate various behaviors by changing the temperature. In this study, degradable hydrogels with thermo-response were designed by reaction of oxidized carboxymethyl cellulose (CMC-CHO) with functional P(NIPAM-co-AH). The hydrogels showed biocompatibility and thermo-response with lower critical solution temperature (LCST) regulated by weight ratio of P(NIPAM-co-AH)/CMC-CHO. The photo-thermal property of gold nanorod was triggered by the near-infrared (NIR) to enhance the DOX release for in vivo anti-tumor therapy of model mice. The results showed good biocompatibility and biodegradability of the hydrogel both in vitro and in vivo, and the DOX with hydrogel loading reduced the toxicity through sustained release behavior. The anti-tumor performance further enhanced with NIR triggered drug release regulated by photo-thermal property. In conclusion, the injectable P(NIPAM-co-AH)/CMC-CHO based self-healing hydrogels could act as promising drug delivery vehicle for potential localized anti-tumor therapy.

Self-healing hydrogel based on polyphosphate-conjugated pectin with hemostatic property for wound healing applications.

Self-healing hydrogels have important application in hemostasis and wound repairing. In this research, pectin based self-healing hydrogel was fabricated with conjugated polyphosphate for hemostatic and wound healing applications. The hydrogel formed without any stimulus and hydrogel kept its biocompatibility; at the same time, the hydrogel degraded completely by enzyme and in vivo. The polyphosphate conjugated hydrogel also showed self-healing property and sustained release performance with strong coagulation characteristic. More importantly, the in vivo experiment revealed that the polyphosphate conjugated hydrogel reduced the blood loss and hemostasis time in hemorrhage model; meanwhile, the hydrogel accelerated the wound repairing rate of the open wound by preventing bacterial invasion. Altogether, the PolyP conjugated hemostatic pectin-based hydrogel is a good candidate as wound dressing material applied in clinic or open wound repairing.

Poly(aspartic acid) based self-healing hydrogel with blood coagulation characteristic for rapid hemostasis and wound healing applications.

External hemorrhage, caused by insufficient hemostasis or surgical failure, could leads to shock or even tissue necrosis as the results of excessive blood loss. Furthermore, delayed coagulation, chronic inflammation, bacterial infection and slow cell proliferation are also major challenges to effective wound repairing. In this study, a novel hemostatic hydrogel was prepared by cross-linking inorganic polyphosphate (PolyP) conjugated poly(aspartic acid) hydrazide (PAHP) and PEO90 dialdehyde (PEO90 DA). Based on the dynamic characteristics of the acylhydrazone bond, the hydrogel could repair its cracks when broken under external forces. At the same time, the hydrogel showed outstanding biocompatibility and tissue adhesion with remarkable hemostatic performance. The New Zealand rabbit ear artery used as a in vivo hemostasis model and the results showed the PAHP hydrogel could stop bleeding of traumatic wound and reduce blood loss significantly. Meanwhile, the PAHP hydrogel presented intrinsic antibacterial activity, thus could inhibit the bacterial infection. In addition, the hydrogel loaded with mouse epidermal growth factor (mEGF) accelerated the wound repair rate and promoted the regeneration of fresh tissue in the mouse full thickness skin defect model. Altogether, the PAHP hydrogels exhibits great potential in the biomedical application, especially in wound dressing materials and tissue repairing.

Light emitting CMC-CHO based self-healing hydrogel with injectability for in vivo wound repairing applications.

Self-healing hydrogels with biodegradability have great potential biomedical application in drug loading and delivery, wound dressing and tissue engineering. In this research, biodegradable hydrogels were designed from oxidized CMC (CMC-CHO) and PEO23 dinaphthoate hydrazide (PEO23 DNH) with naphthalene structure for potential bio-imaging purpose. Results showed that the gelation time of this self-healing hydrogels was very fit for in situ injectable applications for drug loading and controlled release. The hydrogels also showed excellent biocompatibility because all the components and the acylhydrazone bond are biocompatible. Moreover, the in vitro and in vivo drug release study revealed the CMC-CHO based hydrogels could reduce the acute toxicity of the drugs with a controlled and sustained release manner. The hydrogel also showed hemostatic activity by sealing effect and mEGF loaded hydrogel accelerated the wound repairing efficacy. All above result proved the CMC-CHO/PEO23 DNH hydrogel with luminescent property have great application property in bioscience and biotechnology.

Antibacterial Hydrogel with Self-Healing Property for Wound-Healing Applications.

Hydrogels with inherent antibacterial ability are a focus in soft tissue repair. Herein, a series of antibacterial hydrogels were fabricated by quaternized N-[3-(dimethylamino)propyl] methacrylamide (quaternized P(DMAPMA-DMA-DAA)) bearing copolymers with dithiodipropionic acid dihydrazide (DTDPH) as cross-linker. The hydrogels presented efficient self-healing capability as well as a pH and redox-triggered gel-sol-gel transition property that is based on the dynamic acylhydrazone bond and disulfide linkage. Furthermore, the hydrogels showed good antibacterial activity, biocompatibility, degradability, and sustained release ability. More importantly, the in vivo experiments demonstrated that the hydrogels loaded with mouse epidermal growth factor (mEGF) significantly accelerated wound closure by preventing bacterial infection and promoting cutaneous regeneration in the wound model. The antibacterial hydrogels with self-healing behavior hold great potential in wound treatment.

Pectin-based injectable and biodegradable self-healing hydrogels for enhanced synergistic anticancer therapy.

We report a new injectable and biodegradable self-healing hydrogel that shows enhanced anticancer drug release property. The hydrogel was prepared based on biodegradable pectin aldehyde (pectin-CHO) and acylhydrazide functionalized polymer poly(N-isopropylacrylamide-stat-acylhydrazide) P(NIPAM-stat-AH). Due to the dynamic nature of acylhydrazone bonds, the hydrogel exhibits self-healing behavior and its mechanical properties can be regulated by the weight ratio of P(NIPAM-stat-AH) to pectin-CHO. The in vitro and in vivo experiments show the hydrogel has not only good biocompatibility and biodegradability, but also decreases the toxicity of the drugs to living body and exhibits controlled drug release behavior as synergetic anti-tumor drug delivery carriers. The results demonstrate that the pectin-based self-healing hydrogels are injectable, biodegradable, and self-healable that is promising for localized anti-tumor therapy. STATEMENT OF SIGNIFICANCE: Injectable hydrogels with self-healing property and biodegradability are excellent candidates as drug loading and release carrier for biomedical applications. However the pectin as a biobased material is always neglected in self-healing hydrogel preparation. In this study, we fabricated biodegradable self-healing hydrogels from aldehyde group bearing pectin (pectin-CHO) and thermo-responsive copolymer of P(NIPAM-stat-AH). The hydrogel showed sustained drug release behavior, good biocompatibility and biodegradability both in vitro and in vivo. The in vivo experiment shows that the hydrogel with coloaded DOX and CA4 has synergetic therapy to CT26 tumors and this kind of biodegradable hydrogel has great potential application in antitumor therapy.

Hemostatic Self-Healing Hydrogel with Excellent Biocompatibility Composed of Polyphosphate-Conjugated Functional PNIPAM-Bearing Acylhydrazide.

Biocompatible self-healing hydrogels present an effective application as drug-releasing vehicles for tissue engineering and wound repairing. At the same time, the effective hemostatic property of the hydrogels also improves the application property as wound dressing materials. In this research, the PNIPAM-bearing acylhydrazide P(NIPAM-co-AH) was synthesized and then hemostatic polyphosphate (PolyP) was imported to prepare polyphosphate-conjugated P(NIPAM-co-AH) (PNAP). Through the acylhydrazone connection of PNAP and aldehyde functional PEO (PEO DA), the self-healing hydrogel with a hemostatic property was fabricated with good flexibility and sealing effect. The resultant hydrogels kept excellent biocompatibility and showed controlled drug release behavior. More importantly, the hydrogel accelerated the coagulation rate in vitro and presented a strong hemostatic effect as the binder in the hemorrhage model in vivo, which endow the hemostatic hydrogel with a very useful drug delivery carrier for wound healing applications or first aid treatment of the wounded in critical situations.

Poly(aspartic acid) based self-healing hydrogels with antibacterial and light-emitting properties for wound repair.

We report here a self-healing hydrogel with antibacterial and light-emitting properties for wound repair. The hydrogel was prepared by reaction of poly(aspartic acid) (PASP) derivatives bearing groups of quaternary ammonium and boronic acid with poly(vinyl alcohol) (PVA). Due to the dynamic nature of boronic ester bonds, bacteria-killing activity of quaternary ammonium, and light-emitting activity of phenylboronic ester, the resultant hydrogels featured self-healing, antibacterial and light-emitting properties. The hydrogels show controlled release behavior of mouse epidermal growth factor (mEGF) and the in vivo studies show mEGF loaded hydrogel accelerate the wound repair of model mice and improve skin cell proliferation by prevention of bacterial infections. The PASP based hydrogels would show great promise in bio-applications, in particular for wound dressing and tissue repairing.

Fabrication of self-healing hydrogel from quaternized N-[3(dimethylamino)propyl]methacrylamide copolymer for antimicrobial and drug release applications.

Self-healing hydrogels have attracted great attention in recent years because of their wide application in bioscience and biotechnology. In this study, P(DMAPMA-stat-DAA) were synthesized by Reversible Addition-Fragmentation Chain Transfer (RAFT) polymerization and quaternized to import antimicrobial properties. Then quaternized P(DMAPMA-stat-DAA) was used to prepare hydrogel containing acylhydrazone groups with Polyethylene oxide (PEO) diacylhydrazide as a cross-linking agent. The acylhydrazone groups imparted a variety of properties, including group responsiveness and self-healing properties to the hydrogel. At the same time, the quaternary ammonium endowed the hydrogel with the antimicrobial property. The mechanical property, self-healing properties, and antimicrobial property of hydrogels were investigated intensively. Results showed hydrogels formed in neutral conditions, and the luminescent property was introduced with PEO23 dinaphthhydrazide (DNH) cross-linking. The hydrogels showed a controlled pH-sensitive DOX·HC l and Ovalbumin (OVA) release profile. In addition, the hydrogel showed the antimicrobial property and may have important applications in the biomedical field in the near future.