Fabrication of versatile hydrogels in a facile and effective manner represents a pivotal challenge in the field of biomaterials. Herein, a novel strategy is presented for preparing on-demand degradable hydrogels with multilevel responsiveness. By employing selenol-dichlorotetrazine nucleophilic aromatic substitution (SNAr) to synthesize hydrogels under mild conditions in a buffer solution, the necessity of additives or posttreatments can be obviated. The nucleophilic and redox reactions between selenol and tetrazine culminate in the formation of three degradable chemical bonds-diselenide, aryl selenide, and dearomatized selenide-in a single, expeditious step. The resultant hydrogel manifests exceptional adaptability to intricate environments in conjunction with self-healing and on-demand degradation properties. Furthermore, the resulting material demonstrated light-triggered antibacterial activity. Animal studies further underscore the potential of integrating metformin into Se-Tz hydrogels under green light irradiation, as it effectively stimulates angiogenesis and collagen deposition, thereby fostering efficient wound healing. In comparison to previously documented hydrogels, Se-Tz hydrogels exhibit controlled degradation and drug release, outstanding antibacterial activity, mechanical robustness, and bioactivity, all without the need for costly and intricate preparation procedures. These findings underscore Se-Tz hydrogels as a safe and effective therapeutic option for diabetic wound dressings.
Anti-Bacterial Agents , Hydrogels , Wound Healing , Wound Healing/drug effects , Hydrogels/chemistry , Animals , Mice , Anti-Bacterial Agents/pharmacology , Anti-Bacterial Agents/chemistry , Biocompatible Materials/chemistry , Biocompatible Materials/pharmacology , Disease Models, Animal
Photoinduced 3D printing based on the reversible addition-fragmentation chain transfer (RAFT) process has emerged as a robust method for creating diverse functional materials. However, achieving precise control over the mechanical properties of these printed objects remains a critical challenge for practical application. Here, we demonstrated a RAFT step-growth polymerization of a bifunctional xanthate and bifunctional vinyl acetate. Additionally, we demonstrated photoinduced 3D printing through RAFT step-growth polymerization with a tetrafunctional xanthate and a bifunctional vinyl acetate. By adjusting the molar ratio of the components in the printing resins, we finely tuned the polymerization mechanism from step-growth to chain-growth. This adjustment resulted in a remarkable range of tunable Young's moduli, ranging from 7.6â MPa to 997.1â MPa. Moreover, post-functionalization and polymer welding of the printed objects with varying mechanical properties opens up a promising way to produce tailor-made materials with specific and tunable properties.
The periosteum plays a vital role in the regeneration of critical-size bone defects and highly comminuted fractures, promoting the differentiation of osteoblasts, accelerating the reconstruction of the vascular network, and guiding bone tissue regeneration. However, the materials loaded with exogenous growth factors are limited by the release and activity of the elements. Therefore, the material structure must be carefully designed for the periosteal function. Here, a self-adaptive biomimetic periosteum strategy is proposed, which is a novel interpenetrating double network hydrogel consisting of diselenide-containing gelatin and calcium alginate (modified natural collagen and polysaccharide) to enhance the stability, anti-swelling, and delayed degradation of the hydrogel. The diselenide bond continuously releases nitric oxide (NO) by metabolizing endogenous nitrosated thiols (RSNO), activates the nitric oxide-cycle guanosine monophosphate (NO-cGMP) signal pathway, coordinates the coupling effect of angiogenesis and osteogenesis, and accelerates the repair of bone defects. This self-adaptive biomimetic periosteum with the interpenetrating double network structure formed by the diselenide-containing gelatin and calcium alginate has been proven to be safe and effective in repairing critical-size bone defects and is expected to provide a promising strategy for solving clinical problems.
Nitric Oxide , Periosteum , Periosteum/chemistry , Nitric Oxide/analysis , Gelatin/pharmacology , Gelatin/chemistry , Biomimetics , Angiogenesis , Bone Regeneration , Osteogenesis , Alginates , Hydrogels/chemistry , Tissue Scaffolds/chemistry , Tissue Engineering
Covalent adaptable networks (CANs) possess unique properties as a result of their internal dynamic bonds, such as self-healing and reprocessing abilities. In this study, we report a thermally responsive C-Se dynamic covalent chemistry (DCC) that relies on the transalkylation exchange between selenonium salts and selenides, which undergo a fast transalkylation reaction in the absence of any catalyst. Additionally, we demonstrate the presence of a dissociative mechanism in the absence of selenide groups. After incorporation of this DCC into selenide-containing polymer materials, it was observed that the cross-linked networks display varying dynamic exchange rates when using different alkylation reagents, suggesting that the reprocessing capacity of selenide-containing materials can be regulated. Also, by incorporating selenonium salts into polymer materials, we observed that the materials exhibited good healing ability at elevated temperatures as well as excellent solvent resistance at ambient temperature. This novel dynamic covalent chemistry thus provides a straightforward method for the healing and reprocessing of selenide-containing materials.
BACKGROUND: Multifunctional hydrogels with controllable degradation and drug release have attracted extensive attention in diabetic wound healing. This study focused on the acceleration of diabetic wound healing with selenide-linked polydopamine-reinforced hybrid hydrogels with on-demand degradation and light-triggered nanozyme release. METHODS: Herein, selenium-containing hybrid hydrogels, defined as DSeP@PB, were fabricated via the reinforcement of selenol-end capping polyethylene glycol (PEG) hydrogels by polydopamine nanoparticles (PDANPs) and Prussian blue nanozymes in a one-pot approach in the absence of any other chemical additive or organic solvent based on diselenide and selenide bonding-guided crosslinking, making them accessible for large-scale mass production. RESULTS: Reinforcement by PDANPs greatly increases the mechanical properties of the hydrogels, realizing excellent injectability and flexible mechanical properties for DSeP@PB. Dynamic diselenide introduction endowed the hydrogels with on-demand degradation under reducing or oxidizing conditions and light-triggered nanozyme release. The bioactivity of Prussian blue nanozymes afforded the hydrogels with efficient antibacterial, ROS-scavenging and immunomodulatory effects, which protected cells from oxidative damage and reduced inflammation. Further animal studies indicated that DSeP@PB under red light irradiation showed the most efficient wound healing activity by stimulating angiogenesis and collagen deposition and inhibiting inflammation. CONCLUSION: The combined merits of DSeP@PB (on-demand degradation, light-triggered release, flexible mechanical robustness, antibacterial, ROS-scavenging and immunomodulatory capacities) enable its high potential as a new hydrogel dressing that can be harnessed for safe and efficient therapeutics for diabetic wound healing.
The application of reversible deactivation radical polymerization techniques in 3D printing is emerging as a powerful method to build "living" polymer networks, which can be easily postmodified with various functionalities. However, the building speed of these systems is still limited compared to commercial systems. Herein, a digital light processing (DLP)-based 3D printing system via photoinduced free radical-promoted cationic reversible addition-fragmentation chain transfer polymerization of vinyl ethers, which can build "living" objects by a commercial DLP 3D printer at a relatively fast building speed (12.99 cm h-1 ), is reported. The polymerization behavior and printing conditions are studied in detail. The livingness of the printed objects is demonstrated by spatially controlled postmodification with a fluorescent monomer.
Developing biodegradable cationic polymers with high antibacterial efficiency and low cytotoxicity is of great significance in biological applications. Selenium is an essential trace element for the human body, and selenium-containing compounds are promising in various health-related applications. To combine selenium with biodegradability, selenide-functionalized polycaprolactones (PCL) with different hydrophobic substituents were synthesized followed by selenoniumization. The optimal polyselenonium salt showed excellent antibacterial activity with an MBC of 2 µg mL-1 and an MIC of 1 µg mL-1 and exhibited good biocompatibility before and after degradation. In addition, the obtained selenium polymer can be well blended with commercial PCL by electrospinning, and films with good antibacterial activity were prepared. This work enriches the knowledge of selenium derivatives and lays a foundation for follow-up research on selenium cationic polymers in the antimicrobial field.
Anti-Infective Agents , Antineoplastic Agents , Selenium , Humans , Polymers/chemistry , Selenium/chemistry , Anti-Bacterial Agents/chemistry
Photoinduced polymerization is an attractive technique with the advantages of easy operation, mild conditions, and excellent temporospatial controllability. However, the application of this technique in step-growth polymerization is highly challenging. Here, we present a catalyst-free, visible-light-induced step-growth polymerization method utilizing a photo-RAFT single-unit monomer insertion reaction between the xanthate and vinyl ether groups. Benefitting from this reaction, a pendant cationic RAFT agent can be generated in each repeating unit of the polymer backbone. Both cationic and radical side chain extensions were successfully realized, providing a facile approach for the postpolymerization of step-growth polymers for the development of various functional polymeric materials.
Diselenide, as a dynamic covalent bond, has been widely applied in functional materials due to its response to light, heat, sonication, pH, and other stimuli. Herein, a polarization-induced metathesis mechanism for diselenides under heating conditions in the dark is proposed. First, a radical trap experiment is used to prove that the exchange reaction of diselenides in the dark does not involve any radicals. Second, the dynamic exchange reaction of diselenides is found to be affected not only by the polarity of the solvent but also by the introduction of polar groups into the molecular skeleton. Furthermore, DFT calculations also support the notion that polarity has a large effect on the heterolytic rather than homolytic bond dissociation energies. The experimental results for allyl selenide small molecules, polymers, and polymer materials catalyzed by diselenide all support the polarization-induced metathesis mechanism. In short, we successfully enhanced the understanding of the mechanism for diselenide metathesis.
Selenium-containing polystyrene (DSe-PS) microspheres were synthesized by soap-free emulsion polymerization using 1,2-bis(2,3,5,6-tetrafluoro-4-vinylphenyl)diselane (FVPDSe) and divinylbenzene (DVB) as crosslinking agents. The particle size of the obtained DSe-PS was characterized by a scanning electron microscope and dynamic light scattering. The results showed that the diameter of the obtained DSe-PS microspheres could be adjusted by changing the ratio of the monomer and crosslinker/water. The diselenide moiety in the obtained DSe-PS microspheres could be oxidized to seleninic acid by H2O2 which can catalyze the oxidation of acrolein. The oxidized DSe-PS microspheres exhibited higher catalytic activity and selectivity to methyl acrylate in a model oxidation of acrolein.
Polymer molecular weight distribution (MWD) is a key parameter of polymers. Here we present a robust method for controlling polymer MWD in controlled cationic polymerizations. A latent mediator strategy was designed and combined with temporal programming to regenerate mediators at different times during polymerization. Both the breadths and shapes of MWD curves were tuned easily by adjusting an external light source. Bimodal, trimodal, and tetramodal distributions were obtained, and the breadths could be varied from 1.06 to 2.09. Polymers with different MWDs prepared by this method had good chain end fidelity, which was demonstrated with successful chain-extension experiments. In addition, the introduction of temporal programming with a computer-controlled single chip for the light source opened an avenue for the use of artificial intelligence in polymer synthesis.
A new kind of on-demand dissolution hydrogel is successfully synthesized by modification of chitosan using γ-selenobutyrolactone. The chitosan hydrogel with different selenium contents is formed by ring opening of γ-selenobutyrolactone with the amines of D-glucosamine units on the chitosan backbone. The structure of the hydrogel was confirmed by 1H NMR, XRD and XPS. Its physical and biological properties were evaluated by rheology characterization, degradation tests and cytotoxicity test. The hydrogel showed excellent biocompatibility and good degradation properties under oxidation or reduction conditions. All the evidence demonstrated that this type of material has good prospects for dressing applications.
Selenium-containing monomer (p-phenylseleno) styrene (p-PhSeSt) is polymerized by reversible addition-fragmentation chain transfer polymerization. Polymer, (P(p-PhSeSt)), with controlled molecular weight and narrow molecular weight is obtained. The selenide moiety in obtained P(p-PhSeSt) can be selectively oxidized to selenoxide or selenone groups by H2 O2 or NaClO, respectively. These oxidized groups can be further reduced to selenide by Na2 S2 O4 . The structure changing of polymers during such redox cycle is characterized by nuclear magnetic resonance, X-ray photoelectron spectroscopy, and size exclusion chromatography. Properties, such as thermal performance, glass transition temperature, water contact angles, and refractive indices, of the resulting polymers are systematically investigated before and after oxidation. In addition, SiO2 inverse opal photonic crystal (IOPC) is fabricated by sacrificial polymer colloidal template method. Owing to changes of the RIs of P(p-PhSeSt) after selective oxidation, the predictable change of PC bandgap as a redox-responsive PC sensor is successfully realized, which provides new perspectives for modulating photonic crystals.
Silicon Dioxide , Macromolecular Substances , Oxidation-Reduction , Polymerization , Selenium Oxides
Three-dimensional (3D) printing utilizing controlled polymerization systems is emerging as a powerful approach to fabricate "living" objects, which can be further modified with various functionalities. Here, we report photoinduced free radical-promoted cationic reversible addition-fragmentation chain transfer (RAFT) polymerization under broad wavelengths from ultraviolet (UV) to near-infrared (NIR) light. A commercially available iron catalyst, cyclopentadienyl iron dicarbonyl dimer (Fe2(Cp)2(CO)4), was used as the photocatalyst, and several diphenyliodonium salts were examined as oxidants. Various poly(vinyl ether)s with controlled molecular weights and a narrow dispersity (1.06-1.32) were prepared through this method. Relatively high chain-end fidelity can be observed and has been demonstrated by successful chain-extension experiments. In addition, benefiting from the penetrating ability of NIR light, 3D objects with different thicknesses were achieved by employing stereolithography-based 3D printing techniques. Furthermore, the postfunctionalization of these 3D printed objects with fluorescent monomers provides a facile method to build 3D objects with complex functionality and potential applications in anticounterfeiting materials.
Polymers , Printing, Three-Dimensional , Cations , Free Radicals , Iron , Polymerization
We present a robust manganese-catalyzed cationic reversible addition-fragmentation chain transfer (RAFT) polymerization induced by visible light. Well-defined poly(vinyl ether)s with controlled molecular weight and molecular weight distributions (MWDs) can be conveniently prepared at room temperature without monomer purification. The commercially available manganese carbonyl bromide is used as the photocatalyst for cationic RAFT polymerization. Moreover, this method has been further applied in both batch and continuous flow systems, providing a visible light induced flow cationic polymerization under mild conditions.
Manganese , Polymers , Catalysis , Cations , Light , Polymerization
Pendant selenium-containing maleimide polymers with different selenium contents are synthesized via a radical copolymerization of styrene and N-butylmaleimide phenyl selenide. The polymer structures are characterized by nuclear magnetic resonance, gel permeation chromatography, Fourier transform infrared spectroscopy, ultraviolet-visible spectroscopy, and scanning electron microscopy with an energy-dispersive spectrometer, which results in the desired structures and selenium contents. The refractive indices of the polymers, which change as a function of different contents of selenium and oxidative stimuli by H2 O2 or O3 , are investigated. Finally, a photonic crystal (PC) is prepared based on the selenium-containing polymer. The visible color changes of the PC are investigated as a function of different concentrations and contact times of O3 .
Ozone , Selenium , Maleimides , Polymerization , Polymers , Spectroscopy, Fourier Transform Infrared
On-demand dissolution of hydrogels is being increasingly studied for their potential use in burn wound dressing applications. Herein, a dynamic diselenide-containing hydrogel is developed through a very simple one-pot and two-step process starting from the selenol functionalization of a partially hydrolyzed poly(2-ethyl-2-oxazoline) with γ-butyroselenolactone. The hydrogel spontaneously cross-links via an in situ oxidation of the selenol functionalities in air. The gelation process and the final viscoelastic properties of the gel are characterized by rheological experiments. The mechanical properties of those new diselenide-containing hydrogels are easily tuned by varying the concentration of γ-butyroselenolactone. The materials also show good skin adhesion and UV light responsiveness. A unique feature of the hydrogel is its capability to be fully and rapidly dissolved on-demand, via oxidation or reduction of the diselenide cross-links, making them particularly attractive for burn wound dressing applications.
Bandages , Hydrogels , Rheology , Skin
Ring-opening copolymerization (ROCOP) is an effective means to prepare functionalized polyester. In this work, a type of selenide-containing polyesters with controllable structure, molecular weight, and molecular weight distribution was successfully prepared by ROCOP of γ-selenobutyrolactone and epoxy compounds. The influence of the catalyst, solvent, and reaction temperature on the reaction efficiency was examined. Then, kinetic study was investigated under an optimized condition. The structure of the copolymers was carefully characterized by nuclear magnetic resonance (NMR), 1H NMR, 13C NMR, and 77Se NMR, Matrix-assisted laser-desorption-ionization time-of-flight mass spectrometry (MALDI-TOF-MS), and size exclusion chromatography (SEC). The resulting polymers showed a linear structure with a sequence regulated backbone repeating unit of ester-selenide. On this basis, some typical epoxides were investigated to verify the scope of the polymerization system. Due to the "living"/controlled characteristics of this ROCOP, multiblock, amphiphilic, and stereotactic copolymers could be prepared with a pre-designed structure. As expected, the selenide-containing amphiphilic copolymer could self-assemble to micelles and showed an oxidative response.
Stimuli-responsive functional gels have shown significant potential for application in biosensing and drug release systems. In this study, aggregation-induced emission luminogen (AIEgen)-functionalized, diselenide-crosslinked polymer gels were synthesized via free radical copolymerization. A series of polymer gels with different crosslink densities or tetraphenylethylene (TPE) contents were synthesized. The diselenide crosslinker in the gels could be fragmented in the presence of H2O2 or dithiothreitol (DTT) due to its redox-responsive property. Thus, the TPE-containing polymer chains were released into the aqueous solution. As a result, the aqueous solution exhibited enhanced fluorescence emission due to the strong hydrophobicity of TPE. The degradation of polymer gels and fluorescence enhancement in an aqueous solution under different H2O2 or DTT concentrations were studied. Furthermore, the polymer gels could be used as drug carriers, suggesting a visual drug release process under the action of external redox agents. The AIEgen-functionalized, diselenide-crosslinked polymer gels hold great potential in the biomedical area for biosensing and controlled drug delivery.
A near-infrared (NIR) light induced controlled cationic polymerization is presented here. The halide abstraction reaction between the cyclopentadienyl iron dicarbonyl dimer (Fe2(Cp)2(CO)4) and an organic halide is utilized to generate initial radicals or cations under mild conditions, which can be further combined with both radical and cationic reversible addition-fragmentation chain transfer (RAFT) polymerization. Well-defined poly(vinyl ether)s and polyacrylates are prepared successfully under NIR light by this method. The excellent penetration ability of NIR light through thick barriers has been verified by polymerization in the presence of an A4 paper. In addition, iron-based radical polymerization has been used for three-dimensional (3D) printing to fabricate materials with different thicknesses.
