| The physical/chemical properties of the material surface play decisive roles in the cell-material interactions,and therefore affect the therapeutic effects after the implantation of biomaterials.The cells-materials interactions and structures of cells microenvironment are dynamic.Because their physical/chemical properties can respond to changes of signals from external or physiological environments,the intelligent responsive biomaterials can achieve dynamic cell-material interactions and targeting therapies.Among all the physiological environment stimulis,reactive oxygen species(ROS)are closely related to the development of various pathological processes,and their influences are various in different physiological processes.In this study,ROS-related biomaterials responding to stimili both in vitro and in vivo were designed respectively.The changes of their physicochemical properties under stimuli were studied and the therapeutic effects in vivo and in vitro were evaluated.Firstly,UV-responsive monomers pyrenemethyl acrylate was synthesized,followed by copolymerization with acrylic acid to obtain photo-responsive amphiphilic copolymers P(PA-co-AA).The micelles formed by self-assembly of P(PA-co-AA)in water have the same responsiveness,and could form UV-responsive multilayers through layer-by-layer electrostatic self-assembly with positively charged polymers.Under UV irradiation,the disintegration of the micelles due to the cleavage of the pyrenemethyl ester bond caused the increase of surface roughness,hydrophilicity and swelling ratio.Changes above together resulted in promoted adhesion of A549,Hep G2,and EC cells on multilayers in short-term,but had less effects on cell proliferation.Aiming at the bacterial biofilm infection after clinical biomaterials implantion,the micelles formed by P(PA-co-AA)were assembled with chitosans to prepare multilayers for the surface coating of biomaterials.Under UV irradiation,the multilayers also experienced physical/chemical changes such as roughness and hydrophilicity.In addition,a large amount of ROS were generated in-situ in a short time.The in vitro biological evaluation proved that the multilayers had more significant biofilm destruction and anti-bacterial effects(bactericidal rate > 99.999%)than antibiotics.Moreover,the surface after UV irradiation was more conducive to the adhesion and proliferation of EC,FIB,SMC cells.The back subcutaneous implatation model of rats showed that the multilayers coated on silicone slides significantly reduced the density of living bacteria and inflammation after biofilm infection,and therefore,promoted tissue regeneration.Finally,a dexamethasone loaded ROS-responsive and scavenging nanoparticles syetem were designed to for treatment of osteoarthritis.Polythioketals with a ROS-responsive structrue were synthesized,followed by extension of molecular weight by diisocyanate to obtain polythioketal urethanes(PTKU).The chemical structures of PTKU were proved and their thermodynamical,mechanical,fluorescent and material processing properties were characterized.The nanoparticles prepared by the emulsification method could scavenge various types of ROS,and the change of chemical structure,decrease of molecular weight,and change of particle morphology and particle size under ROS were observed.Dexamethasone-loaded PTKU nanoparticles could significantly reduce ROS levels in vitro and in vivo of osteoarthritis,promote the transformation of macrophages into anti-inflammatory phenotype,and help regeneration of osteoarthritis.Here,through the design of ultraviolet light-responsive and ROS-responsive materials,the controlled generation of ROS solved clinical biofilm infections and tissue repair problems,as well as alleviated the inflammatory response in osteoarthritis and promote cartilage regeneration.Preliminary explanation of their mechanisms were given.This paper provides a reference for a comprehensive understanding of the characteristics and functions of ROS in various application scenarios. |
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