Reversible Covalent Bonds Research Articles

Reversible Grafting in Surface Organometallic Chemistry with a Late Transition‐Metal Amidinate Precursor

Supported catalysts are central to industrial catalytic processes. While traditional synthesis methods often yield poorly defined materials, thus complicating structural elucidation, Surface Organometallic Chemistry (SOMC) offers a solution, producing well‐defined structures. Recent advances in SOMC precursor development have shown that amidinate‐based precursors are a privileged class of precursors to generate supported metallic nanoparticles. In that context, this study investigates the grafting mechanism of a prototypical amidinate precursor, Ir(COD)(DIA) (1‐Ir), onto SiO2. Unique to amidinate complexes, grafting is shown to occur without ligand release, creating a reversible covalent bond. Using Ir‐TBOS as a molecular analogue, the structure of the grafted species and the reversibility of the reaction with O‐H groups are demonstrated using IR spectroscopy, single X‐Ray diffraction, variable‐temperature NMR spectroscopy, X‐Ray absorption spectroscopy (XAS), and supported by DFT calculations. Notably, we show that a partial degrafting is also possible at elevated temperatures under vacuum

Organoboron catalysis for direct amide/peptide bond formation.

Amides and peptides are ubiquitous functional groups found in several natural and artificial materials, and they are essential for the advancement of life and material sciences. In particular, their relevance in clinical medicine and drug discovery has increased in recent years. Dehydrative condensation of readily available carboxylic acids with amines is the most "direct" method for amide synthesis; however, this methodology generally requires a stoichiometric amount of condensation agent (coupling reagent). Catalytic direct dehydrative amidation has become an "ideal" methodology for synthesizing amides from the perspective of green chemistry, with water as the only byproduct in principle, high atom efficiency, environmentally friendly, energy saving, and safety. Conversely, organoboron compounds, such as boronic acids, which are widely used in various industries as coupling reagents for Suzuki-Miyaura cross-coupling reactions or pharmaceutical structures, are environmentally friendly molecules that have low toxicity and are easy to handle. Based on the chemical properties of organoboron compounds, they have potential Lewis acidity and the ability to form reversible covalent bonds with dehydration, making them attractive as catalysts. This review explores studies on the development of direct dehydrative amide/peptide bond formation reactions from carboxylic acids using organoboron catalysis, classifying them based on chemical bonding and catalysis over approximately 25 years, from the early developmental days to 2023.

Design and in vitro/in vivo evaluation of chitosan-polyvinyl alcohol copolymer material cross-linked by dynamic borate ester covalent for pregabalin film-forming delivery system

This research introduced a novel polymer synthesized by combining chitosan and modified polyvinyl alcohol, cross-linked with boric acid using dynamic covalent bonds. The polymer was developed to formulate a pregabalin Film-forming system (FFS) for treating postherpetic neuralgia via topical application, showcasing notable skin adhesion and drug delivery properites. The chitosan-boric acid-modified polyvinyl alcohol polymer was analyzed using NMR, FTIR. The exceptional features of the optimized FFS were evaluated through rheometer, Differential scanning calorimetry (Tg = 45.98 °C), contact angle (θ = 78.62°). The elongation (60.05 ± 3.67 %), cohesion (56.94 ± 4.65 MPa) and skin adhesion (58.12 ± 2.99 kPa) of chitosan-boric acid-modified polyvinyl alcohol were found to be 5.2, 6.8, and 8.3 times higher than those of the pure chitosan film, attributed to the double network structure formed by the cross-linked reversible dynamic covalent bond. The optimized pregabalin FFS exhibited increased in vitro (86.25 ± 1.87 μg/g) and in vivo (100.42 ± 7.44 μg/g) skin retention amounts compared to in vivo oral administration (28.43 ± 4.61 μg/g). In summary, the utilization of borate ester dynamic covalent bonds in developing chitosan-based film-forming polymer proved beneficial in improving skin adhesion and topical therapeutic effectiveness, thereby mitigating the risk of systemic side effects associated with oral administration.

Biopolymer immune implants co-loaded with TMZ, R848 and IOX1 for perioperative therapy of glioblastoma

Glioblastoma (GBM), a prevalent and aggressive brain tumor, poses significant treatment challenges due to its rapid progression and the difficulty in achieving complete surgical resection. The current treatment regime, primarily surgery followed by radiotherapy and chemotherapy, offers limited success, with a five-year survival rate of less than 10 %. For addressing the challenges faced in the treatment of GBM, an approach using a biopolymer implant constructed with dynamic reversible covalent bonds, was designed to achieve controlled and constant-rate release of chemotherapy drug (Temozolomide, TMZ), immune adjuvant (Resiquimod, R848) and checkpoint inhibitor (5-carboxy-8-hydroxyquinoline, IOX1). The safety evaluation demonstrated the biocompatibility of the implants, with no significant inflammatory response or adverse effects on various systemic organs. In vivo antitumor study showed that the local delivery of drug combination via this implant significantly inhibited tumor recurrence of orthotopic GBM. Immune analysis revealed that the combination of the three drugs effectively activated systemic antitumor immune responses and induced memory effects. The synergistic mechanism of the drug combination was further validated by RNA whole sequencing. The innovative approach of combining chemotherapy and immunotherapy in biopolymer immune implants for GBM treatment showed promising and opens new avenues for treating GBM, particularly in addressing postoperative recurrence. Statement of significanceOur research introduces a pioneering approach in treating orthotopic brain glioblastoma (GBM), characterized by inevitable tumor recurrence, poor immune infiltration and the restrictive nature of the blood-brain barrier. To break the impasse of ineffective treatment for GBM, the innovative use of dynamically reversible covalent bonds in polymer matrix ensures the controlled, stable and sustained release of drug combinations of the chemotherapeutic agent temozolomide, immune adjuvants and checkpoint inhibitors, which maintains the optimal concentration in the tumor, overcoming problems associated with conventional chemotherapy such as systemic toxicity and low tumor targeting. Empirical evidence from in vivo experiments on the rat GBM model demonstrates significant outcomes: 90 % tumor size reduction and prolonged survival with over 70 % tumor cure rate.

Ordered Carbonaceous Framework Synthesized from Hexaazatrinaphthylene with Enediyne Groups via Solid-State Bergman Cyclization Reaction.

Porous materials synthesized through bottom-up approaches, such as metal-organic frameworks and covalent organic frameworks, have attracted attention owing to their design flexibility for functional materials. However, achieving the chemical and thermal stability of these materials for various applications is challenging considering the reversible coordination bonds and irreversible covalent bonds in their frameworks. Thus, ordered carbonaceous frameworks (OCFs) emerge as a promising class of bottom-up materials with good periodicity, thermal and chemical stability, and electrical conductivity. However, a few OCFs have been reported owing to the limited range of precursor molecules. Herein, we designed a hexaazatrinaphthylene-based molecule with enediyne groups as a precursor molecule for synthesizing an OCF. The solid-state Bergman cyclization of enediyne groups at a low temperature formed a microporous polymer and an OCF, exhibiting redox activity and demonstrating their potential for electrochemical applications. The microporous polymer was used as an active material in sodium-ion batteries, while the OCF was used as an electrochemical capacitor. These findings illustrate the utility of the Bergman cyclization reaction for synthesizing microporous polymers and OCFs with a customizable functionality for broad applications.

Alginate Cryogels for Rapid Hemostasis and Toluidine Blue-Mediated Photodynamic Inactivation of Bacteria.

The development of new wound dressings with fast hemostatic and bactericidal properties for prehospital care is critical. Antibacterial photodynamic therapy (aPDT) has attracted attention due to its broad-spectrum antibacterial activity and minimal bacterial resistance. However, photosensitizers used in aPDT often face issues such as poor water solubility, short-lived singlet oxygen (1O2), and limited 1O2 diffusion range. In this study, sodium alginate was covalently modified with the photosensitizer toluidine blue O (TBO) and phenylboronic acid (PBA). The modified alginate was then cross-linked with Ca(II) ions and lyophilized to form a cryogel, named SA@Ca(II)@TBO@PBA (SCTP). This cryogel functions as an antibacterial photodynamic wound dressing. The chemical immobilization of TBO and PBA enhanced the cryogel's targeting ability. PBA formed reversible covalent bonds with diol groups on bacterial cell surfaces, allowing the cryogel to capture bacteria effectively and enhance aPDT. The bactericidal efficiency of the cryogel was tested through in vitro antibacterial assays, and its hemostatic properties were confirmed in vivo. The results indicate that this cryogel has excellent hemostatic and antibacterial capabilities, showing great promise as a wound dressing for clinical applications.

Photoinduced π-Bond breakage causing dynamic closing-opening shell transition of Z-type Diphenylmaleonitriles molecules

Organic molecules with dynamic covalent-bonding characteristics have attracted much attention for their important role in constructing stimulus-responsive smart materials. However, it is difficult to realize sensitive and reversible covalent bond cleavage/formation through external stimuli in the aggregated state of molecules. Herein, a series of 2,3-diphenylmaleonitriles (DPMNs) with photoinduced π-bond cleavage properties have been designed and synthesized to construct the dynamic covalent bond materials. The cis-form 2,3-diphenylmaleonitriles (Z-DPMNs) exhibit significant photochromism in both solid and solution states under ultraviolet light and visible light. The photochromism stems from the photoinduced π-bond splitting of Z-DPMNs, resulting in a transition from the closed-shell to open-shell structure. Moreover, the twisted structure and molecular stacking of Z-DPMNs, the push-pull electron effect of substituents, and the external factors including temperature and solvent polarity have important effects on the dynamic conversion of π-bonds. Based on the sensitive and reversible optical performance transformation, Z-DPMNs can be applied as safety ink in anti-counterfeiting, information encryption and storage systems. This work not only provides an approach for constructing dynamic covalent bonds but also greatly enriches stimulus-responsive materials.

Use of protease substrate specificity screening in the rational design of selective protease inhibitors with unnatural amino acids: Application to HGFA, matriptase, and hepsin.

Inhibition of the proteolytic processing of hepatocyte growth factor (HGF) and macrophage stimulating protein (MSP) is an attractive approach for the drug discovery of novel anticancer therapeutics which prevent tumor progression and metastasis. Here, we utilized an improved and expanded version of positional scanning of substrate combinatorial libraries (PS-SCL) technique called HyCoSuL to optimize peptidomimetic inhibitors of the HGF/MSP activating serine proteases, HGFA, matriptase, and hepsin. These inhibitors have an electrophilic ketone serine trapping warhead and thus form a reversible covalent bond to the protease. We demonstrate that by varying the P2, P3, and P4 positions of the inhibitor with unnatural amino acids based on the protease substrate preferences learned from HyCoSuL, we can predictably modify the potency and selectivity of the inhibitor. We identified the tetrapeptide JH-1144 (8) as a single digit nM inhibitor of HGFA, matriptase and hepsin with excellent selectivity over Factor Xa and thrombin. These unnatural peptides have increased metabolic stability relative to natural peptides of similar structure. The tripeptide inhibitor PK-1-89 (2) has excellent pharmacokinetics in mice with good compound exposure out to 24 h. In addition, we obtained an X-ray structure of the inhibitor MM1132 (15) bound to matriptase revealing an interesting binding conformation useful for future inhibitor design.

Versatile room temperature phosphorescence polymer with luminophore content as low as 0.05 wt%

To impart processability and practical serviceability to organic room temperature phosphorescence (RTP) molecules, and address phase separation and rigid confinement environment of conventional RTP polymers, a small amount of Schiff base bonds crosslinked tetraphenylene luminescence networks are pinned to the borate ester bonds crosslinked epoxy networks producing reversible interlocked polymer networks-based halogen-free RTP material. By taking advantage of the conjugation interaction of Schiff base linkages, and phase separation inhibition/molecular confinement effects of the interlocking networks, excellent fluorescence quantum yield (up to 78.9 %), RTP lifetime (660 ms) and quantum yield (16.7 %) are achieved with ultra-low concentration of luminophores (0.05 wt%). Moreover, the resultant acquires decent tensile strength (3.8 MPa) and a high elongation-at-break (365 %) owing to its unique molecular design. The phosphorescence lifetimes (457 ∼ 602 ms) are only slightly affected even after cyclic stretching (at 50 % strain for 100 cycles), or soaking in water (for 30 days), or heating (90 °C). The built-in reversible covalent bonds and the topological network reorganization further enable injection molding and self-healing of the material. Having been repeatedly crushed/hot-pressed, the recycled material still shows RTP lifetime and quantum yield of 398 ms and 14.6 %, respectively. The present work provides a feasible approach to fabricate multifunctional robust organic phosphorescent materials with application prospects.

New Advances in Covalent Network Polymers via Dynamic Covalent Chemistry.

Covalent network polymers, as materials composed of atoms interconnected by covalent bonds in a continuous network, are known for their thermal and chemical stability. Over the past two decades, these materials have undergone significant transformations, gaining properties such as malleability, environmental responsiveness, recyclability, crystallinity, and customizable porosity, enabled by the development and integration of dynamic covalent chemistry (DCvC). In this review, we explore the innovative realm of covalent network polymers by focusing on the recent advances achieved through the application of DCvC. We start by examining the history and fundamental principles of DCvC, detailing its inception and core concepts and noting its key role in reversible covalent bond formation. Then the reprocessability of covalent network polymers enabled by DCvC is thoroughly discussed, starting from the significant milestones that marked the evolution of these polymers and progressing to their current trends and applications. The influence of DCvC on the crystallinity of covalent network polymers is then reviewed, covering their bond diversity, synthesis techniques, and functionalities. In the concluding section, we address the current challenges faced in the field of covalent network polymers and speculates on potential future directions.

Dynamic covalent interface engineering for 2D MXene membrane with interchangeable surface groups and tunable layer spacing for water treatment

Two-dimensional (2D) MXene-based materials are promising for water purification due to their nanometer interlayers, however, achieving adaptable and engineerable nanochannel surface properties in the 2D MXene membrane remains challenging. We propose a pioneering approach, called dynamic covalent interface engineering (DCIE), to address this issue. A poly (4-vinylphenylboric acid)-grafted MXene membrane was prepared, binding interchangeable diols via dynamic boronic ester chemistry. Alternative diols enhanced interlayer distancing to 1.49–1.60 nm. The interlayer-anchored diols transition from anionic to cationic and from hydrophilic to hydrophobic states through reversible covalent bond formation and cleavage, with no residue effect of previous diols. As a result, the membrane with swiftly tailored nanochannel properties exhibits exceptional switchable permeability and selectivity (98 % for Congo Red, 97 % for Gentian Violet) for various water treatment scenarios. This innovative method presents a promising strategy for fabricating customizable and switchable 2D MXene-based membranes with enhanced molecular transport and sieving effects, thus advancing water purification applications.

Photoswitchable Cascades for Allosteric and Bidirectional Control over Covalent Bonds and Assemblies.

Studies of complex systems and emerging properties to mimic biosystems are at the forefront of chemical research. Dynamic multistep cascades, especially those exhibiting allosteric regulation, are challenging. Herein, we demonstrate a versatile platform of photoswitchable covalent cascades toward remote and bidirectional control of reversible covalent bonds and ensuing assemblies. The relay of a photochromic switch, keto-enol equilibrium, and ring-chain equilibrium allows light-mediated reversible allosteric structural changes. The accompanying distinct reactivity further enables photoswitchable dynamic covalent bonding and release of substrates bidirectionally through alternating two wavelengths of light, essentially realizing light-mediated signaling cycles. The downfall of energy by covalent bond formation/scission upon photochemical reactions offers the driving force for the controlled direction of the cascade. To show the molecular diversity, photoswitchable on-demand assembly/disassembly of covalent polymers, including structurally reconfigurable polymers, was realized. This work achieves photoswitchable allosteric regulation of covalent architectures within dynamic multistep cascades, which has rarely been reported before. The results resemble allosteric control within biological signaling networks and should set the stage for many endeavors, such as dynamic assemblies, molecular motors, responsive polymers, and intelligent materials.

Engineering bio-brick protein scaffolds for organizing enzyme assemblies.

Enzyme scaffolding is an emerging approach for enhancing the catalytic efficiency of multi-enzymatic cascades by controlling their spatial organization and stoichiometry. This study introduces a novel family of engineered SCAffolding Bricks, named SCABs, utilizing the consensus tetratricopeptide repeat (CTPR) domain for organized multi-enzyme systems. Two SCAB systems are developed, one employing head-to-tail interactions with reversible covalent disulfide bonds, the other relying on non-covalent metal-driven assembly via engineered metal coordinating interfaces. Enzymes are directly fused to SCAB modules, triggering assembly in a non-reducing environment or by metal presence. A proof-of-concept with formate dehydrogenase (FDH) and L-alanine dehydrogenase (AlaDH) shows enhanced specific productivity by 3.6-fold compared to free enzymes, with the covalent stapling outperforming the metal-driven assembly. This enhancement likely stems from higher-order supramolecular assembly and improved NADH cofactor regeneration, resulting in more efficient cascades. This study underscores the potential of protein engineering to tailor scaffolds, leveraging supramolecular spatial-organizing tools, for more efficient enzymatic cascade reactions.

A review on comprehending immunotherapeutic approaches inducing ferroptosis: Managing tumour immunity.

Ferroptosis, a necrotic, iron-dependent controlled cell death mechanism, is distinguished by the development of lipid peroxides to fatal proportions. Malignant tumours, influenced by iron to promote fast development, are vulnerable to ferroptosis. Based upon mounting evidence it has been observed that ferroptosis may be immunogenic and hence may complement immunotherapies. A new approach includes iron oxide-loaded nano-vaccines (IONVs), having supremacy for the traits of the tumour microenvironment (TME) to deliver specific antigens through improving the immunostimulatory capacity by molecular disintegration and reversible covalent bonds that target the tumour cells and induce ferroptosis. Apart from IONVs, another newer approach to induce ferroptosis in tumour cells is through oncolytic virus (OVs). One such oncolytic virus is the Newcastle Disease Virus (NDV), which can only multiply in cancer cells through the p53-SLC7A11-GPX4 pathway that leads to elevated levels of lipid peroxide and intracellular reactive oxygen species leading to the induction of ferroptosis that induce ferritinophagy.

Self‐healing anti‐corrosion coatings: A mechanism study using computational materials science

AbstractSelf‐healing coatings possess the remarkable ability to autonomously mend damages and restore their corrosion protection capabilities, which are compromised due to environmental influences or external forces. The progression of computational materials science has significantly bolstered theoretical explorations into self‐healing anti‐corrosion coatings. Such inquiries enhance our grasp of self‐healing mechanisms, refine coating efficacy, and curtail the expenditures associated with empirical approaches. The research advancements in computational materials science for self‐healing coatings are reviewed here. It delineates the theoretical elucidation of self‐healing mechanisms through the lens of molecular dynamics, density functional theory, Monte Carlo simulations, and finite element analysis. The computational exploration of intrinsic self‐healing coatings primarily involves dynamic reversible covalent bonds, dynamic reversible non‐covalent bonds, and shape memory effect; whereas, extrinsic self‐healing coatings concentrate on the modalities of film‐forming substances and the adsorption behaviours of corrosion inhibitors. These simulation techniques not only shed light on the self‐healing processes at a microscopic scale but also enable the prediction and enhancement of the macroscopic performance attributes of the coatings in practical applications. The merits and constraints of these computational simulation methodologies when applied to self‐healing coatings are critically assessed. Looking ahead, efforts will be directed towards a more profound amalgamation of computational simulations, empirical investigations, and artificial intelligence. This will pave the way for creating a comprehensive database cataloguing the self‐healing properties of coatings, thereby streamlining material selection and design with greater efficiency.

Reprocessable and self-healable boronic-ester based poly(styrene-b-isoprene-b-styrene) vitrimeric elastomer with improved thermo-mechanical property and adhesive performance

It is fascinating to develop vitrimeric elastomers with excellent processability and improved physical properties through incorporating reversible covalent bonds into traditional thermoplastic elastomers. In this work, a poly(styrene-b-isoprene-b-styrene) (SIS) thermoplastic elastomer was selected as the base elastomer and converted into vitrimer through peroxide-induced crosslinking reaction with di-vinyl-terminated boronic ester crosslinker. Kissinger model predicts that the activation energy of vitrimer crosslinking process is slightly higher than that of chemical crosslinking process. The peroxide content was adjusted to tune the composition of permanent chemical crosslinks and dynamic chemical crosslinks. In this way, SIS vitrimer elastomer with tailored multiple network structure was successfully prepared. The stress relaxation behavior of all SIS-BE samples shows Arrhenius-type temperature-dependency and the bond-exchange activation energy (Ea) of SIS-D0.5-B5 sample was estimated as 44.14 kJ/mol. SIS vitrimer elastomer shows improved creep-resistance, comparative mechanical strength and elastic recovery in relative to crosslinked SIS elastomer while maintaining good reprocessbility and self-healing efficiency. Additionally, SIS vitrimeric elastomer shows an increased lap-shear strength from 0.53 MPa to 1.02 MPa with the increase of DCP content. Therefore, we have demonstrated the potential for industrial-scale production of SIS vitrimer elastomer and its applications as reprocessable and healable adhesives.

Self-healing and antistatic waterborne polyurethane hybrid coating resulting from hard but reversible Zr-O-Si networks

Robust, self-healing waterborne coatings have become the preferred choice in the field of flexible electronic devices owing to their outstanding compliance, restorability, and environmental friendliness. Nevertheless, most of the existing self-healing waterborne polymers exhibit viscoelasticity, irreversible fatigue damage, and the challenge of reconciling self-healing functions with mechanical properties, all stemming from inherent molecular structure contradictions between flexibility and rigidity. Here, we propose a novel strategy that utilizes a nanofiller with dynamic reversible bonds to overcome the self-healing limitations that theoretically demand flexible chain, for achieving both mechanical robustness and self-healing ability in the waterborne polyurethane (WPU) hybrid coating system. We modified tetrapropyl zirconate (TPOZ) with 3-aminopropyltriethoxysilane (APTES) to enhance compatibility between the matrix and inorganic particles, while the formation of dynamic reversible bonds through both condensation hydrolysis endows the self-healing abilities. The WPU hybrid coating was designed by covalently incorporating amino-modified TPOZ (A-ZrO2) into a glycinamide-functionalized WPU network, conferring excellent fracture energy (50.3 kJ/m2), elastic recovery, along with antistatic capability to the coating. Furthermore, the hybrid coating maintains a robust mechanical performance alongside 92.58 % of healing efficiency, exhibiting a potential for flexible electronics application. The hybridization strategy via incorporation of the nanofillers with hard but reversible covalent bond resolves the inherent robustness-healing trade-off, providing exciting thoughts to expand WPU applications.

Flexible vanillin-polyacrylate/chitosan/mesoporous nanosilica-MXene composite film with self-healing ability towards dual-mode sensors

Manufacturing flexible sensors with prominent mechanical properties, multifunctional sensing abilities, and remarkable self-healing capabilities remains a difficult task. In this study, a novel vanillin-modified polyacrylate (VPA), which is capable of forming green dynamic covalent crosslinking with chitosan (CS), was synthesized. The synthesized VPA was combined with mesoporous silica-modified MXene (AMS-MXene) and covalently cross-linked simultaneously with CS, resulting in the formation of a flexible composite conductive film designed for dual-mode sensors. Due to the multidimensional structure formed by the mesoporous silica and MXene layers, the resulting composite film is not only suitable for strain sensing but also excels in gas response sensing. Most importantly, the composite films demonstrate a remarkable self-healing capability through reversible dynamic covalent bonds, specifically Schiff base bonds, coupled with multiple hydrogen bonding interactions with AMS-MXene. This robust self-repair functionality remains effective even at a low temperature of 30 °C. Additionally, the synergistic antibacterial effect exerted by vanillin and CS in the film can endow the composite sensor with excellent antimicrobial properties. This multifunctional composite film holds tremendous potential for applications in green flexible wearable sensors. Furthermore, it can show diverse applications in a wide variety of fields, driving advances in wearable technology and human health monitoring.

Innovative Systems for the Delivery of Naturally Occurring Antimicrobial Volatiles in Active Food-Packaging Technologies for Fresh and Minimally Processed Produce: Stimuli-Responsive Materials.

Certain naturally occurring volatile organic compounds are able to mitigate food spoilage caused by microbial growth. Their considerable vapor pressure enables them to create an antimicrobial atmosphere within a package, and this property can be used for the development of active food-packaging technologies. The volatility of these molecules, however, makes their stabilization difficult and limits their effectiveness. Whilst much research is being undertaken on the use of natural antimicrobial volatiles for inhibiting microbial growth in food, less attention has been paid to the design of controlled-release mechanisms that permit the efficient application of these compounds. Most studies to date either spray the volatile directly onto the fresh product, immerse it in a solution containing the volatile, or embed the volatile in a paper disc to create a vapor in the headspace of a package. More sophisticated alternatives would be delivery systems for the sustained release of volatiles into the package headspace. Such systems are based on the encapsulation of a volatile in organic or inorganic matrices (cyclodextrins, electrospun non-wovens, polymer films, micelles, molecular frameworks, etc.). However, most of these devices lack an efficient triggering mechanism for the release of the volatile; most are activated by humidity. All of these techniques are revised in the present work, and the most recent and innovative methods for entrapping and releasing volatiles based on reversible covalent bonds are also discussed.

Mussel inspired sequential protein delivery based on self-healing injectable nanocomposite hydrogel

Polysaccharide based self-healing and injectable hydrogels with reversible characteristics have widespread potential in protein drug delivery. However, it is a challenge to design the dynamic hydrogel for sequential release of protein drugs. Herein, we developed a novel mussel inspired sequential protein delivery dynamic polysaccharide hydrogel. The nanocomposite hydrogel can be fabricated through doping polydopamine nanoparticles (PDA NPs) into reversible covalent bond (imine bonds) crosslinked polymer networks of oxidized hyaluronic acid (OHA) and carboxymethyl chitosan (CEC), named PDA NPs@OHA-l-CEC. Besides multiple capabilities (i.e., injection, self-healing, and biodegradability), the nanocomposite hydrogel can achieve sustained and sequential protein delivery of vascular endothelial growth factor (VEGF) and bovine serum albumin (BSA). PDA NPs doped in hydrogel matrix serve dual roles, acting as secondary protein release structures and form dynamic non-covalent interactions (i.e., hydrogen bonds) with polysaccharides. Moreover, by adjusting the oxidation degree of OHA, the hydrogels with different crosslinking density could control overall protein release rate. Analysis of different release kinetic models revealed that Fickian diffusion drove rapid VEGF release, while the slower BSA release followed a Super Case II transport mechanism. The novel biocompatible system achieved sequential release of protein drugs has potentials in multi-stage synergistic drug deliver based on dynamic hydrogel.