| Objective : To treat the complicated pathological environment of wound healing,the hydrogels,which own unique three-dimensional network structure with high water content,is widely used in soft tissue repair field such as system of drug delivery,tissue engineering and wound dressings.This study aims to develop an innovative but simple design strategy of double network hydrogel based on entanglement effect.The hydrogel can achieve adhesive,self-healing,and highly stretchable and the the application of the gel in the wound healing were evaluated both in vitro and vivo.Methods: PEG-based polymers were chosen as a model and the DN hydrogels can be achieved by combining a covalent PEGDA network with a noncovalent network containing diffusive,long PEG chains.Mc value of the dynamic PEG chains by measuring the viscosity ? of PEG solutions as a function of molecular weight Mw.DN-high hydrogels were prepared by simply mixing 35 kDa PEGDA monomers with PEG of high Mw = 35 kDa in an aqueous solution,followed by radical polymerization of PEGDA in the presence of 0.5% w/v photoinitiator Irgacure 2959.The mechanical properties,the adhesion and self-healing behavior of the DN Hydrogel were measured by conventional tensile tests,lap shear measurements and rheology.Then this hydrogel were used as a two/three-dimensional matrix for cell culture using fibroblast L929 cells to evaluate the biocompatibility of the hydrogel and its potential as an extracellular matrix.Finally,the hydrogel was applied to for both normal or infected wound model of rats,and the therapeutic effect of DN hydrogel was evaluated by histological analysis.Results: The adhesion to substrates including tissue matrices was instant and repeatable due to the diffusive PEG chains that can spontaneously penetrate and entangle with the substrate network.The mechanical properties of DN-high hydrogels were obviously improved and up to 76.0±11.2 kPa,which was 2 times for gel of pure PEGDA.And DN-high hydrogels also has a higher energy dissipation rate(38.9±5.3%).Meanwhile,the DN-high hydrogels have excellent property of adhesion in different substrates such as skin and glasses.When the DN-high hydrogels were cut off and contact just 10 s,it repair themselves and recover favourable mechanical properties.Due to the intrinsic biocompatibility of PEG,after 14 days the L929 cells cultured on/in DN-G hydrogel still survived well and maintained proliferative ability,and there was cell aggregation due to lack of adhesion sites of the hydrogel.In animal experiments,compared to commercial tissue adhesives currently used in clinic,the DN gel effectively accelerated wound healing and significantly reduce immune response in wound bed.In the model of infected wounds,the hydrogels loaded with antimicrobial agents can promote the healing of infected wounds.Conclusion: We reported a new strategy for preparing adhesive,selfhealing,and highly stretchable hydrogels based on the entanglement effects stemming from diffusive giant PEG chains within a double-network system.Studies both in vivo and in vitro have shown that the hydrogel drived by entanglement have excellent potential in wound repair.This new biological material strategy with low technology sensitivity provides a new avenue for the clinical application in wound healing. |
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