Construction Of Functional Hydrogels With Dynamic Covalent Bonds

Gels,a polymer networks with three-dimensional spatial structure,can absorb a large amount of solvent and can be formed with small molecules or macromolecules?including protein molecules?.Although gels have many excellent properties,their ideal properties are often changed or even lost at macroscopic or microscopic cracks,limiting their useful life.In response to this challenge,"smart"soft materials,self-healing gels,have emerged.Smart gels have the ability to respond to external stimuli such as pH,alternating current?AC?,ultraviolet light,temperature,electric and magnetic fields.However,these strong external stimuli hinder their biomedical applications severely in vivo.Hydrogels are a special type of gel in which the swelling agent is water,which has good biocompatibility and water permeability.Hydrogels with different microstructures and properties can be obtained through artificial synthesis.Under mild conditions,enzymes have good biocompatibility with drugs,proteins,and living cells.Compared with the self-healing process that is directly regulated by the acid or other stimulus response,enzyme-controlled self-healing can not only significantly improve the hydrogel repair efficiency,but also maintain the homogeneity of the hydrogel network and the activity of the organism.In addition to simulating biological self-healing function,the simulating living tissues and organs as well as muscle movement is also an important research area.Protein hydrogels have made outstanding contributions in this field.They have many unique characteristics and advantages including inherent bio-friendliness and biodegradability,which can provide artificial micro-environment,highly simulate the key features of living tissues,cell environment,and extracellular matrix.Therefore,inspired by the excellent properties of the enzyme and protein hydrogels,we have constructed several functional hydrogels based on the dynamic chemistry concept?chemical interactions and physical interactions?.It is hoped that these hydrogels will play a potential role in drug delivery,cell proliferation,tissue engineering,biomedical and biomaterials.1.Enzyme-regulated fast self-healing of a pillararene-based hydrogel.Self-healing,one of the exciting attributes of materials,is often used to repair damage to biological and artificial systems.The self-healing process is very common in living organisms.For example,human skin can automatically repair wounds.The enzyme-regulated self-healing method is fast,efficient,and biocompatible.Here,we constructed an enzyme-controlled fast self-healing hydrogel that formed a dynamic hydrazide-linked hydrogel through amino-containing pillar[5]arene-derivant and dialdehyde-functionalized PEG(DF-PEG₄₀₀₀).Then add two enzymes?Glucose oxidase?GOx?and Catalase?CAT??to it.Based on the synergistic action of the enzymes,the hydrogel recovery efficiency and speed are significantly improved.Specifically,the double-enzyme synergistic effect allows the hydrogel to be completely repaired in only about 5 minutes,but it takes more than 1 day for the hydrogel without the dual enzyme system.When the broken hydrogel is treated with a small amount of glucose,the GOx in the hydrogel can reduce the pH of the system by producing gluconic acid,which accelerates the reconstruction of the dynamic hydrazide bond.Subsequently,CAT can decompose hydrogen peroxide?H₂O₂?produced during GOx catalysis process,reducing the effect of H₂O₂ on the mechanical properties of the hydrogel.At the same time,we modify the pyrene-1-carbaldehyde onto the amino-containing pillar[5]arene-derivant and prepare a self-healing conductive hydrogel that can uniformly disperse the single-walled carbon nanotubes?SWCNT?by the?-?interactions between the pyrene and the SWCNT.This not only provides a method for dispersing carbon nanotubes,but also provides a unique method of preparing a conductive hydrogel.This conductive self-healing hydrogel is expected to be widely used in memory devices,drug carriers,biosensors,ultracapacitors,solar cells and other fields.2.Injectable fast self-healing protein hydrogelIt is no exaggeration to say that life is bred,produced,and grown in hydrogels.In organisms,tissues are mostly web gel materials composed of proteins and poly-saccharides that contain large amounts of water,this ensures the efficient delivery of biological substances.Hydrogels with good biocompatibility,water permeability,and different microstructures and properties have a wide range of applications in the biomedical field.Proteins are one of the main substances that sustain the life activities of organisms,and they have complex three-dimensional structures and biological functions.Protein hydrogels are inherently bio-friendly and biodegradable.These properties can promote the development of drug delivery,cell proliferation,tissue engineering,biomedicine,and biomaterials.Here,we reduced the disulfide bonds between BSA protein molecules to form hydrogels by the mismatch of disulfide bonds.The BSA protein hydrogel has efficient and rapid self-healing properties.The broken protein hydrogel only needs 1-2 minutes to fully repair under H₂O₂stimulation response.The self-healing process of BSA protein hydrogel will be accelerated with a little H₂O₂ that is added dropwise at the fracture interface.This is because H₂O₂ can accelerate thiol oxidation.The protein hydrogel has a good shear thinning effect,exhibits fluid properties only under about 39%strain,and has excellent recovery properties.It can be extruded only with a pinhole syringe.The protein hydrogel is expected to find a wide range of applications in drug delivery,tissue engineering,injectable gels,3D bio-printing,and biomedical applications.3.Designed highly stretchable protein hydrogels to mimic the biomechanical behavior of musclesIn living organisms,muscle tissue consists of muscle fibers,which are assembled from many sarcomeres,and sarcomere is mainly composed of thick filaments,thin filaments,and titin that plays a major role in elasticity.During muscle contraction and relaxation,these two myofilaments could slide past each other to achieve functioning not only relying on the precise control of titin as molecular spring,but also related to calcium-ion-induced conformational change in the proteins.Integration of these features endows the muscles with excellent biomechanical behavior,that is,a unique combination of extensibility,strength and resilience.Chemists have been working on mimicking the process of muscle expansion,but simulating elastic muscles with outstanding mechanical properties and biocompatibility remains a big challenge.Here,we introduce physical interactions into chemically cross-linked protein hydrogels,which greatly enhances the tensile properties of protein hydrogels.In combination with the intrinsic and extrinsic characteristics of the protein hydrogels,we successfully simulated the movement of the body's muscles.We used a dynamic covalently crosslinked BSA protein hydrogel to form a network-like hydrogel backbone with an alginate chain,where reversible non-covalent interactions between BSA and alginate chains render the hydrogel excellent stretchability and excellent recovery performance.This is due to the fact that BSA protein can slide along the alginate chain during the stretching process,and the protein structure will unfold as the stretching force increases.It is worth noting that the hydrogel can achieve a 1200%strain at break.The hydrogel has large energy dissipation during the stretching process and it determines the excellent recovery performance.And the contraction recovery process of Ca²⁺-regulated hydrogels is also highly consistent with the natural muscle contraction process.In addition,the protein hydrogel has excellent biocompatibility and is expected to be applied in biomedical materials and tissue engineering in the future,and it contributes to the visual recognition of muscle movement.