Reversible Cross-linking Research Articles

Light-Driven Installation of Aminooxyhomolysine on Histones and Its Application for Synthesizing Stable and Site-Specific 3'-DNA-Histone Cross-Links.

Histones react with various aldehyde-containing DNA modifications to form reversible but long-lived DNA-histone cross-links. The investigation of their biochemical effects and repair mechanisms has been impeded due to their reversibility and the lack of methods for synthesizing stable and structure-defined DNA-histone cross-links. Herein, we present a visible-light-driven strategy to install an aminooxyhomolysine on a histone at a defined position. Using this method, we synthesized a hydrolytically stable and site-specific 3'-DNA-histone cross-link derived from an abasic DNA lesion. Such an adduct can be efficiently repaired by proteolysis coupled with nuclease excision. This work provides a strategy that can be readily expanded to synthesize DNA-histone cross-links derived from other aldehyde-containing DNA modifications.

Fabrication of Zinc(II) Mediated Poly(Acrylamide Co Acrylic Acid) Hydrogel with Thixotropic and Tribological Properties.

Hydrogels have emerged as promising candidates for biomedical applications, such as replacing natural articular cartilage, owing to their unique viscoelastic properties. However, sufficient mechanical properties, self-healing ability, and adhesive nature are some issues limiting its application window. Here, a facile one-pot synthesis of dual cross-linked zinc-coordinated copolymer hydrogels is presented. The network structure of the copolymer hydrogels is strategically developed via dynamic and reversible physical cross-linking by Zn2+ ions and simultaneous covalent cross-linking through a covalent cross-linker viz methylene bisacrylamide. Fourier-transform infrared (FTIR), X-ray diffraction (XRD) scanning electron microscopy (SEM), and Brunauer-Emmett-Teller (BET) analysis have thoroughly characterized the structure of the synthesized hydrogels. The introduction of Zn2+ offers dynamic and reversible complexation, leading to excellent mechanical properties and self-healing features. Moreover, the percentage of the equilibrium water content of zinc-coordinated copolymer hydrogel samples is comparable with that of natural articular cartilage. The Shear sliding study shows the dominant adhesive behavior of HGel-Zn(NO3)2 sample compared to the parent HGel sample. This facile dual cross-linked hydrogel, HGel-Zn(NO3)2, with a combination of good mechanical properties, efficient self-recovery, adequate water content, and favorable adhesive nature, seems very promising to mimic the articular cartilage.

Recyclable Membranes through Reversible and Dynamic Crosslinking

Recyclable Membranes through Reversible and Dynamic Crosslinking

Reinforcement and Controlling the Stability of Poly(ε-caprolactone)-Based Polymeric Materials via Reversible and Movable Cross-Links Employing Cyclic Polyphenylene Sulfide.

Due to its biodegradation ability, poly(ε-caprolactone) (PCL) is a suitable alternative for packaging materials; however, its biodegradation can also lead to instability in its usage. Cyclic polyphenylene sulfide (7U) has been shown to form rotaxane structures with PCL by simple blending to generate the π-π stacking effect and movable cross-link. A 2-fold increase in toughness and no decrease in Young's modulus for the PCL-based polyurethane with 7U are observed. The rotaxane structures mainly exist in the amorphous regions and have no impact on the crystallinity of PCL. Under the catalysis of lipase in aqueous solution, the stability of PCL is improved due to the 7U's suppression of the attack from the enzymes on PCL. After dissolution of the PCL films in the organic solvent, the dispersion of 7U and the breakage of the cross-links lead to little suppression on degradation during the catalysis of lipase. Thus, the controlled stability of PCL using 7U can prolong the life span of the biodegraded PCL materials.

High Self‐Supporting Chitosan‐Based Hydrogel Ink for In Situ 3D Printed Diabetic Wound Dressing

AbstractCustomizable 3D‐printed biopolymer hydrogels, highly sought after for diabetic wound management, face challenges in clinical application due to weak physical crosslinking within their constituent inks. In this study, a novel chitosan‐based hydrogel ink with a dense yet reversible physical crosslinking network is subtly designed for the rapid in situ fabrication of personalized diabetic wound dressing. This robust network is established through multiple electrostatic and hydrogen bonding interactions between unique carboxymethyl chitosan and nanoclay, further reinforced by the introduction of amide bonds, which act as double hydrogen bond donors/acceptors. Benefiting from this network, the ink with low nanoclay content exhibits remarkable self‐supporting properties, enabling high‐fidelity, large‐scale, and complex 3D printability without additional processing, while substantially retaining its inherent rheological properties after autoclave sterilization and the incorporation of active components. Given these advantages, this multifunctional 3D printable hydrogel can be rapidly in situ constructed on diabetic wounds. Simultaneously, the 3D‐printed hydrogel demonstrates biodegradability, anti‐swelling, and appropriate mechanical properties, along with remarkable in vitro antibacterial and pro‐angiogenic capabilities, leading to effective diabetic wound healing in vivo. This work offers a new strategy for creating highly self‐supporting biopolymer inks and paves the way for developing advanced personalized wound dressings.

Bioenergetic-active photoluminescent bioactive Nanodressing for proangiogenic MRSA infected wound repair and microenviroment monitoring

Multidrug-resistant bacterial infected wound repair and real-time microenvironment monitoring are still critical challenges, due to the infection-induced inflammation and poor angiogenesis capacity, as well as the complicate wound microenvironment. Herein, we report a multifunctional photoluminescent bioactive hydrogel (GMCB) with cell bioenergy-supplying and excellent antioxidant activities for achieving infection inflammation wound repair and microenvironment monitoring. GMCB was constructed through a bioenergy-supplying poly(citrate-borate) nanomicelle, antioxidant myricetin and gelatin matrix. GMCB possesses injectable, adhesive, photoluminescent and biodegradable properties, demonstrating excellent cellular biocompatibility. GMCB also shows a pH-responsive photoluminescent change based on the reversible crosslinking between borate and myricetin, which would have the potential to monitoring the pH values of wounds. GMCB significantly promotes the cell migration, upregulates the expression of angiogenesis-related genes, efficiently clears reactive oxygen species, and inhibits the expression of inflammatory factors. Importantly, GMCB could release citrate to accelerate the cellular bioenergetics by enhancing mitochondrial membrane potential and ATP levels providing energy for multiple biological activities of cells. GMCB accelerates the repair of methicillin-resistant Staphylococcus aureus (MRSA) infected inflammatory wounds by inhibiting early-stage inflammation, promoting neovascularization and collagen deposition. This work provides a feasible strategy to design bioenergy-reinforcing and intelligent dressing for wound repair-monitoring integration.

Toughening Healable Supramolecular Double Polymer Networks Based on Hydrogen Bonding and Metal Coordination.

Double polymer networks (DNs) consist of two interpenetrating polymer networks and can offer properties that are not merely a sum of the parts. Here, we report an elastic DN made from two supramolecular polymers (SMPs) that consist of the same poly(n-butyl acrylate) (BA) backbone. The two polymers feature different non-covalent binding motifs, which form dynamic, reversible cross-links. The polymers were prepared by reversible addi-ti-on-frag-mentation chain-transfer polymerization of n-butyl acrylate and either the self-complementary hydrogen-bonding motif 2-ureido-4[1H]pyri-mi-dinone, or the 2,6-bis(1'-methyl-benz--imidazolyl)-pyridine ligand, which forms complexes with metal ions. The supramolecular DN made by these components combines features of the single networks, including high thermal stability and resistance to creep. The DN further exhibits excellent healability and displays a higher extensibility and a higher toughness than its constituents. The mechanical characteristics of the DN can be further enhanced by selectively pre-stretching one of the networks, which is readily possible due to the reversible formation of the supramolecular cross-links and their orthogonal stimuli-responsive-ness.

Reversible Vitrimisation of Single‐Use Plastics and their Mixtures

AbstractVitrimers are promising next‐generation materials, often exhibiting superior properties such as mechanical strength and solvent resistance compared to their thermoplastic counterparts, while still featuring recyclability due to their dynamic covalent crosslinks. The most common strategy to recycle vitrimers is via mechanical reprocessing at high temperatures, while others utilize chemical degradation to reobtain the constituent monomers. This work presents a new approach toward reprocessing by selectively breaking of the vitrimer's crosslinks, turning it back into a thermoplastic. This allows for reprocessing to be achieved in a more sustainable manner such as at lower temperatures and shorter times. After the desired shape has been obtained, facile re‐crosslinking turns the material into a vitrimer, with full restoration of thermal stability, mechanical properties, and gel fraction. To achieve this, a carbene C─H insertion strategy is utilized to introduce an imine‐based crosslinker into various thermoplastics and plastic mixtures to convert them into vitrimers. Properties typical of vitrimers such as a retained polymer network at high temperatures, and an Arrhenius‐type relationship between stress relaxation rate and temperature are observed, while its mechanical properties such as elongation at break and tensile toughness, particularly for plastic mixtures are significantly enhanced, first by crosslinking, then further enhanced up to 8 folds by the reversible crosslinking process.

Reversibly crosslinked polyurethane fibres from sugar-based 5-chloromethylfurfural: Synthesis, fibre-spinning and fibre-to-fibre recycling.

The development of recyclable crosslinked thermosetting fibres is a challenging research topic. In the present work, we have designed and synthesized polyurethane fibres from fructose-derived 5-chloromethylfurfural (CMF) and lignin-derived monomeric phenols. The greenhouse gas emissions associated with the production of CMF showed comparable results to that of 5-hydroxymethylfurfural (HMF), a high potential sugar-based platform molecule. The wet-spun biobased polyurethane fibres produced could be conveniently crosslinked using Diels-Alder chemistry to effectively enhance the glass transition temperature and mechanical properties. At a mildly elevated temperature (140 °C), the chemically crosslinked fibres could be effectively de-crosslinked, which enabled complete separation from a mixture with poly(ethylene terephthalate) (PET) and cotton fibres. These results outline a potential strategy to design and fabricate new biobased fibres with reversible crosslinking, which may enable fibre-to-fibre recycling.

A multifunctional self-reinforced injectable hydrogel for enhancing repair of infected bone defects by simultaneously targeting macrophages, bacteria, and bone marrow stromal cells

Injectable hydrogels (IHs) have demonstrated huge potential in promoting repair of infected bone defects (IBDs), but how to endow them with desired anti-bacterial, immunoregulatory, and osteo-inductive properties as well as avoid mechanical failure during their manipulation are challenging. In this regard, we developed a multifunctional AOHA-RA/Lap nanocomposite IH for IBDs repair, which was constructed mainly through two kinds of reversible cross-links: (i) the laponite (Lap) crystals mediated electrostatic interactions; (ii) the phenylboronic acid easter bonds between the 4-aminobenzeneboronic acid grafted oxidized hyaluronic acid (AOHA) and rosmarinic acid (RA). Due to the specific structural composition, the AOHA-RA/Lap IH demonstrated superior injectability, self-recoverability, spatial adaptation, and self-reinforced mechanical properties after being injected to the bone defect site. In addition, the RA molecules could be locally released from the hydrogel following a Weibull model for over 10 days. Systematic in vitro/vivo assays proved the strong anti-bacterial activity of the hydrogel against Staphylococcus aureus (S. aureus) and Escherichia coli (E. coli). Moreover, its capability of inducing M2 polarization of macrophages (Mφ) and osteogenic differentiation of bone marrow stromal cells (BMSCs) was verified either, and the mechanism of the former was identified to be related to the JAK1-STAT1 and PI3K-AKT signaling pathways and that of the latter was identified to be related to the calcium signaling pathway, extracellular matrix (ECM) receptor interaction and TGF-β signaling pathway. After being implanted to a S. aureus infected rat skull defect model, the AOHA-RA/Lap IH significantly accelerated repair of IBDs without causing significant systemic toxicity. Statement of significanceRosmarinic acid and laponite were utilized to develop an injectable hydrogel, promising for accelerating repair of infected bone defects in clinic. The gelation of the hydrogel was completely driven by two kinds of reversible cross-links, which endow the hydrogel superior spatial adaption, self-recoverability, and structural stability. The as-prepared hydrogel demonstrated superior anti-bacterial/anti-biofilm activity and could induce M2 polarization of macrophages and osteogenic differentiation of BMSCs. The mechanism behind macrophages polarization was identified to be related to the JAK1-STAT1 and PI3K-AKT signaling pathways. The mechanism behind osteogenic differentiation of BMSCs was identified to be related to the ECM receptor interaction and calcium signaling/TGF-β signaling pathways.

Conductive, injectable, and self-healing collagen-hyaluronic acid hydrogels loaded with bacterial cellulose and gold nanoparticles for heart tissue engineering

The increasing demand for advanced biomaterials in nerve tissue engineering presents numerous challenges due to the complexity of nerve tissues and the need for materials that can accurately replicate their intricate structure and function. In response, this study introduces a novel injectable hydrogel that is thermosensitive, self-healing, and conductive, offering promising potential for heart and nerve tissue engineering applications. The hydrogel is based on collagen and hyaluronic acid functionalized with 3-aminopropyl-triethoxysilane (APTES)-grafted oxidized bacterial cellulose and gold nanoparticles (~50 nm). Rheological analysis reveals a substantial enhancement in the elastic modulus of the collagen-hyaluronic acid matrix with the incorporation of bacterial cellulose/gold nanoparticles, improving by an order of magnitude at 1 % strain. This improvement comes with a slight decrease in gelation temperature, from 36 °C to 32 °C. Besides thermo-sensitivity, the nanocomposite hydrogel exhibits a remarkable self-sealing response (about 80 % effectiveness) due to reversible physical crosslinking. Electrical spatial resistance measurements on human embryonic stem cell-derived cardiomyocytes-loaded hydrogels yield a value of ~0.1 S/m, which is suitable for electrical stimulation. In vitro extracellular field potential measurements also affirm the hydrogel's potential as an injectable scaffold for heart tissue engineering, i.e., the electrically stimulated human stem cells exhibit 47 beats per minute with a cell discharge (depletion) of 5.47 μv. A rapid gel formation in the physiological temperature (about 2 min) and high H9C2 cytotoxicity (viability of >90 % after 72 h incubation) is attainable. The developed collagen-based nanocomposite hydrogel offers an injectable, thermosensitive, and self-healing biomaterial platform for nerve or myocardium regeneration.

Reversible Disulfide Bond Cross-Links as Tunable Levers of Phase Separation in Designer Biomolecular Condensates.

Biomolecular condensates (BCs) are membraneless hubs enriched with proteins and nucleic acids that have emerged as important players in many cellular functions. Uncovering the sequence determinants of proteins for phase separation is essential in understanding the biophysical and biochemical properties of BCs. Despite significant discoveries in the past decade, the role of cysteine residues in BC formation and dissolution has remained unknown. Here, to uncover the involvement of disulfide cross-links and their redox sensitivity in BCs, we designed a "stickers and spacers" model of phase-separating peptides interspersed with cysteines. Through biophysical investigations, we learned that cysteines promote liquid-liquid phase separation in oxidizing conditions and perpetuate liquid condensates through disulfide cross-links, which can be reversibly tuned with redox chemistry. By varying the composition of cysteines, subtle but distinct changes in the viscoelastic behavior of the condensates were observed. Empirically, we conclude that cysteines function neither as stickers nor spacers but as covalent nodes to lower the effective concentrations for sticker interactions and inhibit system-spanning percolation networks. Together, we unmask the possible role of cysteines in the formation of biomolecular condensates and their potential use as tunable covalent cross-linkers in developing redox-sensitive viscoelastic materials.

Self-healing and thermal transport behavior in catalytic vitrimer-graphene composite

Vitrimers are a distinct category of polymers that could conduct dynamic cross-linking in response to temperature stimuli. In this work, using a molecular dynamics simulation model, we explore self-healing and the thermal transport behavior of vitrimer-graphene composites to overcome its inherent slow self-healing process. The temperature-dependent reversible cross-link mechanisms, which possess the capacity to dynamically modify the mechanical properties of these substances, are studied by explicitly integrating the temperature-dependent reaction probabilities. This modeling approach efficiently predict the changes in the mechanical properties of vitrimers when undergoing temperature cycling both above and below the topological freezing point, as well as the damage healing and subsequent recuperation of mechanical behaviors. The heat transport behavior of the graphene-vitrimer composite is investigated using non-equilibrium molecular dynamics in conjunction with self-healing models. The thermal conductivity of vitrimer-graphene composites, calculated by including a bilayer graphene sheet with varied flake size and interlayer spacings, exhibits a considerable enhancement as compared to standalone vitrimers. Notably, the thermal conductivity is subject to change when the separation distance changes. These results shed light on the self-healing and heat transmission in vitrimer and open the door to possible applications in several fields, including electronics, energy efficiency, aerospace, and materials research.

Mussel-inspired tough ionogel with robust adhesion and mechanical adaptivity for impact resistance

Intrinsic adhesiveness and mechanical adaptivity allowing spontaneous anchoring and impact-stiffening, which facilitate safer impact protection, remain challenges for the design and synthesis of advanced tough impact-resistant materials. Herein, a novel biomimetic mechanically robust impact-resistant ionogel with the mussel-inspired diphasic structure was elaborately developed. The salt-bridge hydrogen bonds between carboxyl and imidazole groups inside rigid clusters serve as reversible crosslinking sites and prime energy-dissipation motifs, leading to strong noncovalent cohesion. Furthermore, the hydrophobic ionic liquid enriches surface interactions, providing extensive adhesive performance for in-situ attachment under external impact. Benefitting from the dynamic nature of the salt-bridge hydrogen bonds, the ionogel possesses impressive energy dissipation, self-healing, and recyclable properties. Notably, the prepared ionogel exhibits rate-dependent mechanical adaptivity and outstanding impact-stiffening performance with extraordinary initial modulus (∼6.3 GPa), impact strength (∼178.5 MPa), and impact toughness (∼89.6 MJ m−3) under high-speed impact (∼5200 s−1). This work offers promising biomimetic design inspirations for the future development of advanced, flexible, sustainable, and protective materials.

Closed-Loop Recyclable Poly(ester-disulfide)s for Potential Alternatives to Engineering Plastic.

Facile fabrication, low material complexity and closed-loop recycling are essential for polymer plastics to alter their linear product economy towards a cradle-to-cradle one. Covalent adaptable networks (CANs) are one way to achieve that, which intrinsically exhibit decent mechanical properties like the thermosets but could also be easily recycled like the thermoplastics. In this work, we introduce rigid ester structural motifs into dynamic poly(disulfide)s to form a series of dual polymer networks. Owning to the coherence of soft/rigid segments and the reversible sacrificial crosslinking, they exhibit tailorable mechanical properties and good resistance towards different chemicals. Their closed-loop recycling is achieved via mild solvolysis, maintaining materials' mechanical integrities. It offers a solution as a sustainable replacement for engineering plastics which are massively under production but hard to be recycled.

The effects of ACR/MAH ionic cross-linking on the cell morphology, mechanical properties, and dimensional stability of PVC foams

This study details a novel approach to enhance the dimensional stability of foamed polyvinyl chloride (PVC) materials through the introduction of a reversible cross-linking network. This is achieved via the carboxylation of acrylate polymers (ACR) utilizing the hydrolysis reaction of maleic anhydride (MAH) during the extrusion of PVC foam sheets. Subsequently, an ionic cross-linking network is formed using calcium-zinc (Ca-Zn) stabilizers. This paper elucidates the process of cell formation and the mechanisms underpinning the ACR/MAH ion network formation. Cell morphology of the foamed PVC was characterized using SEM, and the effects of ionic cross-linking on the plasticizing time, dimensional stability, and mechanical properties were analyzed through cell diameter distribution measurements and rheometry. The longitudinal and transverse dimensional shrinkage of PVC-F/MAH1 was reduced by 28.0 % and 28.9 %, respectively. The construction of the ACR/MAH ion cross-linking network not only augments the mechanical properties but also substantially enhances the dimensional stability of the material. This approach underscores the viability of ion cross-linking networks in advancing the performance parameters of PVC foams, suggesting a promising avenue for future research and development in polymer processing technology, and potentially expanding their application spectrum.

Biomass-derived dynamic polyurethanes: Enhanced self-healing and recyclability through reversible cross-linking

Chemically cross-linked polyurethanes (CCPUs), renowned for their superior solvent resistance, high strength, and exceptional thermostability, have emerged as extensively used polymeric materials. Despite their advantages, CCPUs face a significant limitation that their stable cross-linked structures can preclude healing and recycling once damaged. This limitation underscores the urgent need for a new CCPUs variant that offers self-healing and recyclability to extend service life. In this work, a new type of cross-linked polyurethanes (CPUs) was designed and synthesized by incorporating the biomass-derived castor oil (CO) as a cross-linking agent and dynamic disulfide bond into a traditional polyurethane without using any catalysts. These newly developed CPUs exhibit superior mechanical performance with an impressive tensile strength of 29.37 MPa and a remarkable maximum elongation at break of 769.9 %. Notably, our recycled CPU-2 can retain a tensile strength of 22.40 MPa and an elongation at break above 604.8 % even after four thermal recycling cycles. Furthermore, the addition of conductive carbon black (CB) into this CPU matrix imparts remarkable self-healing properties to the polyurethanes/carbon black composite (CPU-2/CB), activated solely by near-infrared light. This inventive approach effectively enhances the functionality of traditional CCPUs, broadening their application potential.

Commodity Rubber Material with Reversible Cross-linking Ability: Application of Boroxine Cross-links to Ethylene-Propylene Rubber

Commodity Rubber Material with Reversible Cross-linking Ability: Application of Boroxine Cross-links to Ethylene-Propylene Rubber

Stretchable Piezoresistive Pressure Sensor Array with Sophisticated Sensitivity, Strain-Insensitivity, and Reproducibility.

This study delves into the development of a novel 10 by 10 sensor array featuring 100 pressure sensor pixels, achieving remarkable sensitivity up to 888.79kPa-1, through the innovative design of sensor structure. The critical challenge of strain sensitivity inherent is addressed in stretchable piezoresistive pressure sensors, a domain that has seen significant interest due to their potential for practical applications. This approach involves synthesizing and electrospinning polybutadiene-urethane (PBU), a reversible cross-linking polymer, subsequently coated with MXene nanosheets to create a conductive fabric. This fabrication technique strategically enhances sensor sensitivity by minimizing initial current values and incorporating semi-cylindrical electrodes with Ag nanowires (AgNWs) selectively coated for optimal conductivity. The application of a pre-strain method to electrode construction ensures strain immunity, preserving the sensor's electrical properties under expansion. The sensor array demonstrated remarkable sensitivity by consistently detecting even subtle airflow from an air gun in a wind sensing test, while a novel deep learning methodology significantly enhanced the long-term sensing accuracy of polymer-based stretchable mechanical sensors, marking a major advancement in sensor technology. This research presents a significant step forward in enhancing the reliability and performance of stretchable piezoresistive pressure sensors, offering a comprehensive solution to their current limitations.

Gene therapy by virus-like self-spooling toroidal DNA condensates for revascularization of hindlimb ischemia

Peripheral arterial diseases (PAD) have been reported to be the leading cause for limb amputations, and the current therapeutic strategies including antiplatelet medication or intervene surgery are reported to not clinically benefit the patients with high-grade PAD. To this respect, revascularization based on angiogenetic vascular endothelial growth factor (VEGF) gene therapy was attempted for the potential treatment of critical PAD. Aiming for transcellular delivery of VEGF-encoding plasmid DNA (pDNA), we proposed to elaborate intriguing virus-like DNA condensates, wherein the supercoiled rigid micrometer-scaled plasmid DNA (pDNA) could be regulated in an orderly fashion into well-defined nano-toroids by following a self-spooling process with the aid of cationic block copolymer poly(ethylene glycol)-polylysine at an extraordinary ionic strength (NaCl: 600 mM). Moreover, reversible disulfide crosslinking was proposed between the polylysine segments with the aim of stabilizing these intriguing toroidal condensates. Pertaining to the critical hindlimb ischemia, our proposed toroidal VEGF-encoding pDNA condensates demonstrated high levels of VEGF expression at the dosage sites, which consequently contributed to the neo-vasculature (the particularly abundant formation of micro-vessels in the injected hindlimb), preventing the hindlimb ischemia from causing necrosis at the extremities. Moreover, excellent safety profiles have been demonstrated by our proposed toroidal condensates, as opposed to the apparent immunogenicity of the naked pDNA. Hence, our proposed virus-like DNA condensates herald potentials as gene therapy platform in persistent expressions of the therapeutic proteins, and might consequently be highlighted in the management of a variety of intractable diseases.