Construction And Functional Applications Of Elastic Electrospun Nanofibrous Hydrogels

Hydrogels are three-dimensional networks made of cross-linked hydrophilic polymers that could hold a large amount of water.Hydrogels are attractive for wide applications in fields of tissue engineering,wound healing,drug delivery,and electronic devices,due to their integrated properties of high water content,biocompatibility,and responsiveness to external stimuli.However,traditional hydrogels lack tissue-like fibrous structures and mechanical properties（e.g.,extracellular matrix,muscle,and heart tissue）,which makes it difficult to further improve their functionality and broaden their application areas.Nanofibers in biological soft tissues,such as collagen microfibers and elastic fibers in extracellular matrix and oriented collagen fiber bundles in skeletal muscle,provide exceptional mechanical properties and functionality for biological tissues.The unique fibrous structures in biological soft tissues have inspired researchers to construct nanofibrous structured hydrogels for improving the mechanical properties and biological functions of hydrogels.Nanofiber-based hydrogels include nanofiber/hydrogel composites and hydrogel nanofibers.Nanofiber/hydrogel composites can be prepared by introducing nanofibrous membranes or dispersed nanofibers into the hydrogel matrix.Hydrogel nanofibers can be prepared by self-assembly,repeated freeze-thawing,template synthesis,and electrospinning methods.Among the above methods,electrospinning has become the most popular method to prepare hydrogel nanofibers,owing to facile process,ease of scalable synthesis from different polymers,and tunable fiber structure.Moreover,electrospinning can also prepare a variety of functional non-hydrogel nanofiber materials（such as ceramic nanofibers and carbon nanofibers）,followed by combination with the hydrogel matrix to form nanofiber/hydrogel composites with various nanofiber structures.However,these materials suffer from poor stretchability and elasticity as well as low bioactivity,which cannot meet the mechanical integrity and biological activity requirement for practical applications.Therefore,the construction of elastic,stretchable,and bioactive electrospun nanofiber-based hydrogels remains a great challenge,and is of great importance for their practical applications in the fields of flexible sensors and biomedicine.In this paper,we focused on the preparation and functional applications of the elastic electrospun nanofiber-based hydrogels.The elastic and stretchable electrospun nanofibrous hydrogels with physically and chemically cross-linked network structure were prepared.The relationship between the double cross-linked networks and the mechanical properties of the hydrogels was systematically investigated.Moreover,a mechanically robust transparent nanofiber-reinforced hydrogel was constructed by using the flexible electrospun SiO₂ nanofibers as reinforcing component.The innovative strategy was to synthesize soft hydrogel matrices from acrylamide monomers in the presence of well-dispersed silica nanofibers and vinyl silane,which generated homogenous nanofiber-reinforced hydrogels with innovative interfacial chemical bonds.The effects of interfacial energy and strength between SiO₂ nanofibers and the hydrogel matrix on the mechanical properties of the hydrogels were studied,and their applications in strain sensing were investigated.Furthermore,flexible bioactive glass nanofibrous membranes were prepared by sol-gel electrospinning,and then bioactive glass nanofiber-based hydrogels were constructed by freeze-drying method.The self-expansion behavior,mechanical properties,bioadhesion ability,and hemostasis performances of the bioactive glass nanofiber-based hydrogels were systematically investigated.The main research results obtained are as follows:（1）The nanofibrous hydrogel membranes with dermis-mimicking network structure were prepared by electrospinning using waterborne polyurethane（WPU）as the elastic reinforcing component,ethanol-soluble zein as the hydrogel component,trimethylolpropane tris（2-methyl-1-aziridine propionate）（TTMA）as a crosslinker,and ethanol as the green solvent.TTMA was introduced into a hybrid electrospinning solution and the robust covalent cross-linking was constructed between zein and WPU by a subsequent thermally crosslinking process.The water-swollen hydrogel membranes maintained the nanofiber structural integrity with an average fiber diameter of 390 nm and a pore size of 0.42μm.Benefiting from the strong hydrogen bonding and chemical cross-linking between zein and polyurethane,the as-prepared nanofiber hydrogels exhibited the integrated mechanical characteristics of a stretch of 683%,a fracture strength of 6.5MPa,and a toughness of 20.7 MJ m^-3.During the deformation process,the dynamic chain entanglement readily dissociated and the hydrogen bonds were broken easily,serving as stress buffers to dissipate energy.Meanwhile,the strong covalent bonding between zein and WPU chains maintained the network structural integrity under large deformations,preventing the hydrogels from nonrecoverable damage.The nanofibrous hydrogel membranes showed good elasticity and tensile fatigue resistance,and the stress remains 79%of the initial state after 100 tensile cycles.（2）The chemically integrated silica-nanofiber-reinforced hydrogels（SFRHs）with robust mechanical and electronic performance were prepared by an in situ synthesis strategy.The strategy was to synthesize soft hydrogel matrices from acrylamide monomers in the presence of well-dispersed silica nanofibers and vinyl silane,which generated homogenous SFRHs with innovative interfacial chemical bonds.The interaction energies were quantitatively analyzed using a molecular dynamic Perl script.After introducing robust covalent bonding,the interfacial energy of the composite hydrogel significantly increased.The resultant SFRHs exhibited excellent mechanical properties including high mechanical strength of 0.3 MPa at a fracture strain of 1400%,high Young’s modulus of 0.11 MPa（comparable to human skin）,and superelasticity over 1000 tensile cycles without plastic deformation,while maintaining high transmittance（≥83%）.The SFRHs also showed robust compressive resilience and high compressive stress（2.6 MPa at 90%strain）.Moreover,the SFRHs showed high ionic conductivity(3.93 S m^–1)and could detect a broad range of strains（0.5–1100%）and pressures（1–28 k Pa）with robust sensitivity（GF of 2.67）and ultra-durability（10000 cycles）,which make them promising soft sensors for detecting various body movements,human pulse,and handwriting.（3）Flexible bioactive glass（69.5SiO₂-24.5Ca O-6P₂O₅ wt%）nanofibers were constructed by sol-gel electrospinning with the assistant of polymer template.The nanofibers had an amorphous structure with uniform distribution of the elements,resulting in few defects in the single nanofibers.And the nanofiber membranes had a Young’s modulus of 1.2 MPa,a tensile fracture stress of 0.23MPa,and a tensile strain of 6.4%.The bioactive glass nanofiber membranes were then homogenized in polyvinyl alcohol solution with citric acid as the cross-linking agent.The dispersions were freeze-dried into 3D nanofibrous hydrogel with hierarchical porous structure.These bioactive glass nanofibrous cryogels（BGNCs）exhibited high absorption capacity（～3100%）,fast self-expanding ability,near zero Poisson’s ratio,injectability,high compressive recovery at a stain of 80%,and robust fatigue resistance（plastic deformation of 0%after 800 cycles at a strain of 60%）.Moreover,the BGNCs could form stable adhesion on diverse tissue surfaces with high shear strength（approximately 7.32 k Pa for heart,5.09 k Pa for stomach,5.03 k Pa for muscle,and 6.49 k Pa for skin）,which is much higher than those of commercially available gelatin sponges.Moreover,the BGNCs presented high blood clotting,blood cell adhesion,and coagulation pathway activation ability.In addition,BGNCs exhibited superior capacity in stopping rabbit liver,femoral artery,and rat heart hemorrhages as compared with commercial gelatin hemostatic sponges.Furthermore,the BGNCs could effectively promote the angiogenesis and wound healing in the rat full-thickness skin wound model.