Chitosan-based Biomedical Materials:Controllable Construction,Properties And Applications

Chitosan(CS)is the only basic polysaccharide in nature,and has been widely used in biomedical fields.Chitosan-based biomedical materials can be tailored with various forms and versatile functions by chemical modification and exploration of preparation techniques.However,the controllable construction of chitosan-based biomedical materials is still very challenging,which is manifested by its poor processability,inadequate mechanical properties,and operation inconvenience.Therefore,selective construction of CS-based biomedical materials with prominent properties for different clinical demands is of great significance for solving practical clinical problems and expanding the application field of chitosan materials.In this paper,chitosan was selected as the main substrate,and a series of CS-based biomedical materials with different forms and excellent performance were constructed according to the clinical issues in different application fields.Specific research contents are listed as follows:(1)Poor periodontal regeneration is mainly caused by root absorption and bone ingrowth adhesion of non-functional cells,which further hinders the formation of new bone tissue.To solve this problem,a pure CS-based bio-mimetic double-layer composite materials with asymmetric structure was constructed via novel microgel self-deposition technique.This CS composite materials were composed of a porous layer and a dense layer.Its microstructure and mechanical properties can satisfy the criteria for guided tissue regeneration(GTR)membrane.Materials properties could be tune by deacetylation degree(D.D)adjustment.The rat skull defect model was applied to estimate the in vivo bone regeneration performance.The micro-CT and histological results manifested that CS double-layer composites with high D.D exhibited outstanding bone regenerative ability and superior degradation compatibility over the commercialized Bio-gide~?membrane.(2)The poor healing capacity and potential peritendinous adhesion of injured tendons has made tendon repair as a primary clinical concern.Rat tendon stem/progenitor cells(TSPCs)were first incorporated with CS double-layer composites for tendon regeneration.CS double-layer composites with high D.D and molecular weight has excellent tensile properties under dry/wet conditions.It showed positive tendinous gene and protein expression adjustment for TSPCs.The higher production of collagen I(COL1)and tenomodulin(TNMD),higher biomechanical properties and lower adhesion score for Achilles tendon repair model demonstrated that the CS double-layer composites were capable of inducing conspicuous tenogenic differentiation and superior phenotypic maturity.The introduction of TSPCs into the CS scaffold resulted in a synergistic effect on tendon regeneration and yielded better-aligned collagen fibers with elongated,spindle-shaped cells.(3)Aiming for the clinical emergency hemostasis problem of massive carotid arterial bleeding and internal bleeding,a CS-based hydrogel hemostatic adhesive(CCS@gel)were constructed with injectable,self-healing and rapid gelation properties.CCS@gel can form gel rapidly at the bleeding site(t<15 s).In vitro mechanics and adhesion performance evaluation,in vitro compatibility evaluation(cell,blood,tissue),rat splenic/liver bleeding model and carotid artery bleeding model were used to verify the hemostatic plugging effect.Compared with commercialized fibrin glue,CCS@gel had better hemostasis effect on a variety of anticoagulant visceral wounds and carotid bleeding.In addition,due to the unique self-contractile characteristics of CCS@gel under physiological conditions,it could achieve long-term wound sealing and promote wound closure.(4)Considering the early detection of cancer cells,smart systems with stimulus triggered features have become increasingly popular nowadays.On account of the highly reductive micro-environment in tumor tissues,a redox-responsive fluorescent AIE bioprobe based on CS was designed and synthesized.This AIE bioprobe possessed excellent water dispersibility and nano-size stability under physiological conditions.Under the reductive microenvironment of tumor cells,the water dispersibility of the AIE probe becomes worse owing to the cleavage of carboxyl groups.The dispersibility alteration further induces the aggregation of AIE nanoparticles and enhances intracellular retention,allowing for targeted imaging reinforcement and selective suppression of cancer cells.