Schiff Base Interactions Research Articles

Injectable and self-healing sulfated hyaluronic acid/gelatin hydrogel as dual drug delivery system for circumferential tracheal repair

Stem cell-based therapies show promise for clinically addressing circumferential tracheal defects (CTD) through tissue engineering. However, creating a tissue-engineered tracheal tube possesses a healthy cartilage matrix and intact tube structure remains a challenge. A solution lies in the use of an injectable hydrogel with shape adaptability and chondrogenic capacity, serving as a practical and dependable platform for tubular tracheal cartilage regeneration. In this study, we developed an injectable hydrogel using modified natural polymers-hydrazide-grafted gelatin (Gelatin-ADH) and aldehyde-modified hyaluronic acid with sulfated groups (HA-CHO-SO3) via Schiff Base interaction. Additionally, aldehyde-modified β-cyclodextrin (β-CD-CHO) was introduced into the network during hydrogel formation. The negative sulfated groups and hydrophobic cavities of β-cyclodextrin facilitated the efficient encapsulation and sustained release of transforming growth factor-β1 (TGF-β1) and kartogenin (KGN) within our hydrogel. This synergistically promoted the chondrogenesis of loaded bone marrow stem cells (BMSCs). Subsequently, we employed this TGF-β1, KGN, and BMSCs loaded hydrogel to form a cartilage ring. This ring was then assembled into an engineered tracheal cartilage tube using our previously reported ring-to-tube strategy. Our results demonstrated that the engineered tracheal cartilage tube effectively repaired CTD in a rabbit model. Hence, this study introduces a novel hydrogel with significant clinical application potential for tracheal tissue engineering.

Schiff base linkage of citral to zinc-casein hydrolysate chelates for preparing starch-based active films against L. monocytogenes on ready-to-eat foods

Listeria monocytogenes (L. monocytogenes) is a foodborne pathogen often found in ready-to-eat (RTE) foods, posing significant threats to human health. In this study, an active film based on cross-linking via Schiff base and electrostatic interaction to inactivate L. monocytogenes on RTE foods was constructed. Zinc-casein hydrolysate chelates (Zn-HCas) was prepared and blended with cationic starch (CSt) to form the substrates of the film. Then, Citral (CI) with excellent antibacterial properties was added to enhance the biological and packaging properties of the film through covalent cross-linking (Schiff base). Based on the zinc ion-activated metalloproteinases produced by L. monocytogenes, the cross-linked film could be disrupted and the release of CI was accelerated. The variation in color, FTIR, and amino group content proved that Schiff base reaction had taken place. Enhanced mechanical properties, barrier properties, thermal stability and antimicrobial activity against L. monocytogenes (exceed 99.99 %) were obtained from the CI/Zn-HCas/CSt film. The application on RTE cheese results demonstrated that the cross-linked film could be employed in active packaging field with the ability in maintaining the original chroma and texture properties of RTE cheese. In summary, the prepared cross-linked film could be used as an active packaging against L. monocytogenes contamination with great potential.

Multifunctional organohydrogel via the synergy of dialdehyde starch and glycerol for motion monitoring and sign language recognition

Conductive hydrogel which belongs to a type of soft materials has recently become promising candidate for flexible electronics application. However, it remains difficult for conductive hydrogel-based strain sensors to achieve the organic unity of large stretchability, high conductivity, self-healing, anti-freezing, anti-drying and transparency. Herein, a multifunctional conductive organohydrogel with all of the above superiorities is prepared by crosslinking polyacrylamide (PAM) with dialdehyde starch (DAS) in glycerol-water binary solvent. Attributing to the synergy of abundant hydrogen bonding and Schiff base interactions caused by introducing glycerol and dialdehyde starch, respectively, the organohydrogel achieved balanced mechanical and electrical properties. Besides, the addition of glycerol promoted the water-locking effects, making the organohydrogel retain the superior mechanical properties and conductivity even at extreme conditions. The resultant organohydrogel strain sensor exhibits desirable sensing performance with high sensitivity (GF = 6.07) over a wide strain range (0–697 %), enabling the accurate monitoring of subtle body motions even at −30 °C. On the basis, a hand gesture monitor system based on the organohydrogel sensors arrays is constructed using machine learning method, achieving a considerable sign language recognition rate of 100 %, and thus providing convenience for communications between the hearing or speaking-impaired and general person.

ROS/pH dual responsive PRP-loaded multifunctional chitosan hydrogels with controlled release of growth factors for skin wound healing

Platelet-rich plasma (PRP) contains a variety of growth factors (GFs) and has been used in the treatment of a variety of diseases, including skin lesions. In particular, PRP with low immunogenicity will be more widely used. However, the explosive release of GFs limits its further application. In order to achieve controlled release of GFs, a multifunctional and reactive oxygen species (ROS)/pH dual responsive hydrogel was developed to load PRP derived from human cord blood for the treatment of skin wound healing. Based on the hydrogen bond and Schiff base interaction, carboxymethyl chitosan (CMCS), oxidized dextran (Odex) and oligomeric procyanidins (OPC) were crosslinked to form CMCS/Odex/OPC/PRP hydrogel with good injectability, self-healing, adhesion, ROS scavenging, antibacterial activity, controlled and sustained release of GFs. In vitro cell experiments suggested that this hydrogel possessed excellent biocompatibility and could promote the proliferation and migration of L929. In vivo healing of full-layer skin wounds further indicated that the prepared hydrogel could regulate inflammation and promote epithelialization, collagen deposition, and angiogenesis. In summary, this present study demonstrates that CMCS/Odex/OPC/PRP hydrogel may serve as a promising multifunctional dressing for skin wound healing.

Vanillin cross-linked chitosan/gelatin bio-polymer film with antioxidant, water resistance and ultraviolet-proof properties

Cross-linking is the most promising method for preparing high-performance chitosan/gelatin bio-polymer film. In this work, vanillin cross-linked chitosan/gelatin bio-polymer (CGGV) film with good mechanics, water resistance, antioxidant and ultraviolet-proof property was prepared. The micro-structure, physical and functional properties of CGGV film were studied. Results showed that vanillin as a cross-linking agent provided a compact inner micro-structure through Schiff base and hydrogen bond interaction. Moderate cross-linking significantly improved mechanical strength, thermal ability, hydrophobicity of the films and reduced the water vapor permeability, swelling ratio and water solubility. Especially, CGGV films showed stronger ultraviolet-proof properties and possessed potent radical scavenging activity. Therefore, CGGV film is suitable to protect per-mature fruits and could be used as novel multifunctional packaging in the agriculture and foods industry.

A double cross-linked hydrogel based on water-soluble chitosan and oxidized hyaluronic acid as an antibacterial dressing

Quaternary ammonium chitosan (QCS) is a cationic polymer with high antimicrobial properties, but its cations can cause damage to normal cells. Thus, the biocompatibility of QCS in hydrogel dressings should be concerned. In this study, QCS was used as an additive in the preparation of the carboxymethyl chitosan (CMC) and oxidized hyaluronic acid (OHA) hydrogel, and the effect of its content in the hydrogel on antibacterial and biocompatibility was systematically investigated. First, QCS was mixed at a different ratio with CMC to form a QCS/CMC solution. Then, the QCS/CMC solution was added into the OHA solution to obtain the OHA-CMC/QCS hydrogel, which is a double cross-linked network formed by the Schiff base and electrostatic interaction. With the increase of the QCS content in the hydrogel, its mechanical and antibacterial properties were enhanced. The antibacterial rate of OHA-CMC/QCS5 hydrogel with 5% QCS content against Staphylococcus aureus reached 99.80%, and it also showed biocompatibility under the experimental conditions. This work provides a theoretical basis for the use of QCS to prepare the hydrogels that are both antibacterial and biocompatible. The prepared OHA-CMC/QCS5 hydrogel is an ideal candidate for antimicrobial dressings.

Composite Hydrogel Dressings with Enhanced Mechanical Properties and Anti-Inflammatory Ability for Effectively Promoting Wound Repair.

Hydrogel dressings have been used as a crucial method to keep the wound wet and hasten the healing process. Due to safety concerns regarding the gel components, low mechanical adhesiveness, and unsatisfactory anti-inflammatory capacity qualities for practical uses in vivo, leading to the clinical translation of wound dressings is still difficult. A type of composite hydrogel (acrylamide/polyethylene glycol diacrylate/tannic acid, ie, AM/PEGDA/TA) by double bond crosslinking, Schiff base, and hydrogen bond interaction is proposed. The mechanical characteristics, adhesiveness, and biocompatibility of the hydrogel system were all thoroughly examined. Additionally, a full-thickness cutaneous wound model was employed to assess the in vivo wound healing capacity of resulting hydrogel dressings. Benefiting the mechanism of multiple crosslinking, the designed composite hydrogels showed significant mechanical strength, outstanding adhesive capability, and good cytocompatibility. Moreover, the hydrogel system also had excellent shape adaptability, and they can be perfectly integrated into the irregularly shaped wounds through a fast in situ forming approach. Additional in vivo tests supported the findings that the full-thickness wound treated with the composite hydrogels showed quicker epithelial tissue regeneration, fewer inflammatory cells, more collagen deposition, and greater levels of platelet endothelial cell adhesion molecule (CD31) expression. These above results might offer a practical and affordable product or method of skin wound therapy in a medical context.

Enhancing the properties of electrospun polyvinyl Alcohol/Oxidized sodium alginate nanofibers with fluorescence carbon Dots: Preparation and characterization

The objective of this study was to develop fluorescence nanofibrous polyvinyl alcohol/oxidized sodium alginate (PVA-OSA) incorporated with carbon dots (CDs) through Schiff-base interaction. The carbon dots used in this study were derived from the polyphenol-enriched extract of pomegranate peel, as established in previous work, as the reinforcing and antioxidant agent to enhance the physicochemical and biological properties of the nanofibers were used. The fabricated nanofibers were characterized using FE-SEM, FT-IR, XRD, and DSC analysis. The FE-SEM results revealed that an increase in the number of CDs in the nanofibers led to a decrease in diameter (809.6 ± 77.1 nm to 273.16 ± 41.1 nm). Furthermore, surface modification caused a significant reduction in the amount of surface roughness of the nanofibers. Incorporating CDs not only reduced the scaffold diameter but also improved its mechanical properties and promoted the growth of fibroblast cells. The ultimate tensile strength of scaffolds with and without CDs was 2.15 ± 0.02 MPa and 1.53 ± 0.74 MPa respectively. The influence of CDs amount on the properties of nanofibers showed that the swelling capacity and degradability of nanofibers can be adjusted by changing the range of CDs. Apart from the aforementioned benefits of incorporating CDs in improving nanofiber properties, their exceptional antioxidant properties can be harnessed for protecting nanofibers against oxidation and as a healing agent in wound dressings.

Laponite stabilized endogenous antibacterial hydrogel as wet-tissue adhesive

Clinical adhesives for suture-less wound closure remain the problem of poor biocompatibility, weak adhesive strength, and no endogenous antibacterial ability. Here, we designed a novel antibacterial hydrogel (CP-Lap hydrogel) consisting of chitosan and ε-polylysine after being modified with gallic acid (pyrogallol structure). The hydrogel was crosslinked by glutaraldehyde and Laponite via Schiff base and dynamic Laponite-pyrogallol interaction, free from heavy metal and oxidants. Given its dual crosslinking feature, the CP-Lap hydrogel exhibited adequate mechanical strength (150–240 kPa) and demonstrated swelling and degradation resistance. For a typical lap shear test with pigskin, the apparent adhesion strength of the CP-Lap hydrogel could be enhanced to ∼30 kPa benefiting from the O2 blocking effect provided by nanoconfinement space between Laponite. In addition, the hydrogel showed effective antibacterial properties and excellent biocompatibility. The results indicated that this hydrogel has great potential for wound-closing bioadhesives to avoid chronic infections and further harm.

Characterization and bio-functional performance of chitosan/poly (vinyl alcohol)/trans-cinnamaldehyde ternary biopolymeric films

Bioactive films of chitosan (CS)/polyvinyl alcohol (PVA)/trans-cinnamaldehyde (CIN) were prepared by co-blending, and the impact of varying concentrations (0.5, 1.0 and 1.5 %) of CIN on the physicochemical properties of the ternary films was investigated. The ATR/FT-IR analysis revealed that the bioactive film is modulated by Schiff base (C=N) and hydrogen-bond interactions of CS, PVA, and CIN. Inclusion of CIN into the film improved mechanical properties with tensile strength increased from 0.5 % (68.52 MPa) to 1.5 % (76.95 MPa). The presence of CIN within the CS/PVA film also remarkably affected oxygen permeability and improved light transmittance. Additionally, the water barrier and contact angle properties were improved with increasing CIN content. The morphology of the CIN-containing films appeared non-stratified and dense when observed by SEM and AFM. Moreover, spore germination and in vitro assays confirmed strong antifungal activity of the CIN-containing film against P. italicum (~90 %) and B. cinerea (~85 %). The ternary films also exhibited excellent antioxidant activity, as evidenced by DPPH radical scavenging activity (31.43 %) and ferric reducing power (OD700 nm = 0.172) at the highest CIN concentration tested. Thus, this bioactive CIN films are proposed as a versatile packaging material for the food industry.

Glycopeptide‐Based Multifunctional Hydrogels Promote Diabetic Wound Healing through pH Regulation of Microenvironment

AbstractExcessive inflammation, bacterial infection, and blocked angiogenesis make diabetic wound healing challenging. Multifunctional wound dressings have several advantages in diabetic wound healing. In addition, the pH regulation of the microenvironment is shown to be a key factor that promotes skin regeneration through cellular immune regulation. However, few reports have focused on the development of functional dressings with the ability to regulate the pH microenvironment and promote diabetic wound healing. This study presents a novel approach for regulating the pH microenvironment of diabetic wound sites using a glycopeptide‐based hydrogel consisting of modified hyaluronic acid and poly(6‐aminocaproic acid). This hydrogel forms a network through Schiff base interactions and metal complexation, which suppresses inflammation and accelerates angiogenesis during wound healing. Hydrogels not only have adequate mechanical properties and self‐healing ability but can also support tissue adhesion. They can also promote the secretion of inducible cAMP early repressor, which promotes the polarization of macrophages toward the M2 type. The in vivo results confirm that hydrogel promotes diabetic wound repair and skin regeneration by exerting rapid anti‐inflammatory effects and promoting angiogenesis. Therefore, this hydrogel system represents an effective strategy for treating diabetic wounds.

Injectable and self-healing double network polysaccharide hydrogel as a minimally-invasive delivery platform

Injectable hydrogels exhibiting self-healing ability are promising carriers for controlled and sustained delivery in a minimally-invasive format for biomedical applications. We designed a polysaccharide-based double network hydrogel by mixing solutions of aldehyde-alginate (aAlg) and acrylic acid-chitosan (aCS) in the presence of adipic acid dihydrazide and FeCl2 that resulted in dual crosslinking mediated by Schiff base and ionic interactions. The hydrogel exhibited excellent thixotropic and self-healing properties with a high compressive fracture strength of ≈ 48 kPa. Encapsulated cells were viable within the hydrogel, and after their release from the degraded gel. The controlled release of Doxorubicin and Ciprofloxacin from the hydrogels established the gel as a delivery platform. The released drugs were effective in killing cancer cells or arresting the growth of both bacteria. This work presents a self-healing and injectable degradable hydrogel that may be used as a minimally-invasive platform for the delivery of drugs and cells.

Dual stimuli-responsive nanocarriers based on polyethylene glycol-mediated schiff base interactions for overcoming tumour chemoresistance

Multifunctional and stimulus-sensitive intelligent nanodrug delivery systems (NDDSs) can significantly optimize the effectiveness of theranostic agents for cancer treatment. In this study, redox and pH dual-responsive nanocarriers (CPNPs) were prepared through molecular assembly by utilizing the Schiff base interactions of cystamine (Cys), PEG-NH2 and formaldehyde (FA) under aqueous conditions with a one-pot, one-step technique. First, the degradation products of CPNPs exhibited good biocompatibility, and the high concentration of intact CPNPs (200 µg/mL) could inhibit the growth of cells. In addition, doxorubicin (DOX) was encapsulated in CPNPs simply by changing the pH (DOX@CPNPs), and pH/GSH-responsive release behaviour was confirmed. In vitro, CPNPs significantly increased the uptake of DOX and enhanced the cytotoxicity of DOX to tumour cells. More importantly, DOX@CPNPs strongly reversed drug resistance in three different types of cancer cells, exhibiting significant anticancer effects. Collectively, this study presents the easy preparation of nanomedicines that respond to multiple stimuli, which highlights the advantages of Schiff base-based nanomedicines for cancer therapy and reversing chemoresistance.

Microspheres powder as potential clinical auxiliary materials for combining with platelet-rich plasma to prepare cream gel towards wound treatment

Platelet-rich plasma (PRP), which contains several growth factors (GFs), is used clinically in various wound treatments. To promote treatment efficacy of PRP in wound healing, the present study is inspired by the spreadable feature of commonly used creams in dermatology, developing a microspheres powder, which can be used easily to combine with PRP to form a cream gel. The microspheres powder is composed of hydroxy propyl chitosan (CSPO) microspheres and oxidized alginic acid (OALG) microspheres. Due the advanced permeability among microspheres that caused by larger specific surface area and abundant gaps, by simply adding PRP into microspheres powder, even without stirring, a granular gel is immediately formed based on electrostatic action and Schiff base interaction between OALG microspheres and CSPO microspheres, as well as fibrin network formed by PRP and thrombin. The PRP-granular gel exhibited bulk hydrogel feature, while it's shear-thinning and self-healing performance makes it behave like creams, thus can be applied to the whole wound area via spread. Besides, due to the charge action and Schiff base interaction, the PRP-granular gel can attach on the wound, ensuring PRP functions on the wound. Subsequently, in vivo evaluation confirms that the PRP-granular gel can promote the healing of skin wounds. Further transcriptome sequencing suggests that the PRP-granular gel can change the expression of multiple genes in wound tissue by which it can alter the process of wound healing. In a word, the present study demonstrates the great potential of transforming this gel into the next generation of PRP-based bioactive wound dressing.

Dual‐Crosslinked Dynamic Hydrogel Incorporating {Mo154} with pH and NIR Responsiveness for Chemo‐Photothermal Therapy (Adv. Mater. 40/2021)

Photothermal Materials In article number 2007761, Shiqi Wang, Hélder Santos, and co-workers introduce a polyoxometalate {Mo154}-incorporating, dual-crosslinked dynamic hydrogel (Mo154Gel) formed by Schiff base and electrostatic interactions. Mo154Gel shows exceptional photothermal conversion, and pH- and near-infrared-laser-triggered drug release. This work paves the way for the development of novel {Mo154}-based platforms incorporated in self-healing and injectable hydrogels for combinatorial chemo-photothermal cancer therapy.

Dual-Crosslinked Dynamic Hydrogel Incorporating {Mo154 } with pH and NIR Responsiveness for Chemo-Photothermal Therapy.

Polyoxometalates are an emerging class of molecular clusters, with well-defined structures and chemical compositions that are produced through simple, low-cost, and highly reproducible methods. In particular, the wheel-shaped cluster {Mo154 } is a promising photothermal agent due to its intervalence charge transfer transitions. However, its toxicity hinders its systemic administration, being the development of a localized delivery system still incipient. Herein, an injectable and self-healing hydrogel of easy preparation and administration is developed, incorporating both {Mo154 } and doxorubicin for synergistic photothermal and chemotherapy applications. The hydrogel is composed of benzylaldehyde functionalized polyethylene glycol, poly(N-isopropylacrylamide) functionalized chitosan and {Mo154 }. The gelation occurs within 60s at room temperature, and the dual crosslinking by Schiff base and electrostatic interactions generates a dynamic network, which enables self-healing after injection. Moreover, the hydrogel delivers chemotherapeutic drugs, with a release triggered by dual near infra-red (NIR) radiation and pH changes. This stimuli-responsive release system along with the photothermal conversion ability of the hydrogel allows the simultaneous combination of photothermal and chemotherapy. This synergic system efficiently ablates the cancer tumor in vivo with no systemic toxicity. Overall, this work paves the way for the development of novel {Mo154 }-based systems, incorporated in self-healing and injectable hydrogels for dual chemo-photothermal therapy.

Polydopamine-modified SnO2 nanofiber composite coated QCM gas sensor for high-performance formaldehyde sensing

This paper introduces a quartz crystal microbalance sensor (QCM) based on SnO2 NFs/PDA composite with multi-layer stacked fiber nanostructure, which possesses high sensitivity and selectivity to formaldehyde gas. SnO2 NFs/PDA composite was synthesized via electrospinning and further oxidative polymerization. The morphology and chemical compositions of the as-prepared composite nanomaterials were confirmed by a series of material characterization technologies. The QCM sensor based on SnO2 NFs/PDA nanomaterials exhibited excellent sensing characteristics over a wide range of formaldehyde concentration (0.5 − 50 ppm), such as high sensitivity (12.2 Hz/ppm), short response/recovery times (25 s/38 s), high linearity and selectivity. The frequency shift characteristics and electrical parameters of the prepared sensors were confirmed by impedance analysis. The adsorption mechanism of formaldehyde gas could be attributed to hydrogen bonding and the combination of aldehyde ammonia Schiff base interactions. This work indicated that SnO2 NFs/PDA based QCM possessed great potential in actual formaldehyde sensing, which provided a feasible solution for designing highly sensitive and selective formaldehyde sensor.

Synthesis and characterization of a manganese(II) complex containing N(sp 2)4-donor Schiff base ligand and interaction toward biomacromolecules

In this work, an N4-donor Schiff base ligand, N,N'-(propane-1,2-diyl)bis(1-phenyl-1-(pyridin-2-yl)methanimine) (PPPM) and its Mn(II) complex, [Mn(PPPM)(OAc)2]·3H2O (1), were prepared and identified by elemental analysis, FT-IR, 1H NMR spectroscopy as well single-crystal X-ray diffraction. X-ray structure analysis of 1 revealed a distorted square-face bicapped trigonal prism geometry around manganese atom with MnN4O4 environment containing an N4-donor PPPM and two O2-donor acetato ligands. The ligand has a chiral center on carbon atom which leads to the formation of a racemic mixture of complex 1. In the crystal structure of complex, intermolecular hydrogen bonds form R4 4(8) hydrogen bond motifs. The ability of two optical isomers of PPPM ligand and manganese complex to interact with 10 selected biomacromolecules (BRAF kinase, CatB, DNA gyrase, HDAC7, rHA, RNR, TrxR, TS, Top II, B-DNA) was investigated by docking studies. These studies revealed that PPPMR,S and 1 R,S isomers can bind to these molecules better than doxorubicin (except B-DNA).

Preparation of antifogging and enhanced antimicrobial biopolymer coating and its applications in lettuce preservation

This study focused on the development of a new biopolymer coating with antifogging and antimicrobial properties. The dual functional coatings, which consisted of multiple layers of chitosan (CS) and alginate dialdehyde (ADA), were prepared by layer-by-layer assembly driven by Schiff base, hydrogen bonding, and electrostatic interactions. Fourier transform-infrared spectroscopy indicated the formation of a Schiff base between CS and ADA. The six-layer coating had high transparency, optimum hydrophilicity and antifogging property as characterized by spectroscopy, water contact angle analysis and antifogging testing. The antibacterial activity of the six-layer coating was better than that of CS alone. Furthermore, the six-layer coating reduced decay of fresh-cut lettuce during storage. The results from this study suggest that coatings consisting of CS and ADA can prevent fogging, inhibit microbial growth, and maintain the quality of fresh produce throughout storage.

Materials design and sensing mechanism of novel calix[6]arene composite for sensitively detecting amine drugs

In order to improve the convenience and sensitivity of amphetamines drug testing and reduce the threat of drugs to humans, we have designed a QCM gas sensor to detect amine-containing drugs. The sensing material is designed based on the chemical nature of amine drugs. The sensing mechanism is derived from a reversible Schiff base interaction between the amino group of the drug and the carbonyl group of the novel calix[6]arene derivatives as well as the hydrogen bond interaction between amino group and hydroxyl. The new composite material was well characterized by different analytical techniques including 1H nuclear magnetic resonance (1H-NMR), fourier transform infrared spectroscopy (FT-IR), scanning electronic microscopy (SEM), transmission electron microscope (TEM), Raman spectra, powder X-ray diffraction, etc. The sensing experiments were conducted by coating the composite onto quartz crystal microbalance (QCM) transducers. The experimental results indicated that the novel calixarene derivatives and their GO complexes based on the design have excellent selectivity, high sensitivity and repeatability to β-phenylethylamine.