Preparation Of Bioactive Ceramic Composites And Its Antibacterial Activity And Regenerative Repair Effect

The treatment of tissue defects and related infections,especially infections caused by drug-resistant bacteria and biofilms,has always been a difficult problem in the medical field.There are few biomaterials that can inhibit bacterial infection and promote tissue repair at the same time.Studies have found that the combined use of two antibacterial materials with different antibacterial mechanisms is more effective than using one antibacterial agent alone,and can reduce the production of new drug-resistant bacteria.In addition,the inhibition of bacteria not only relies on antibacterial materials,but also can be achieved by using immune cells,the enemy of bacteria.If materials can stimulate the conversion of macrophages to the M1 phenotype,immune antibacterial can be achieved,and the development of drug resistance in bacteria can be reduced.Bioactive ceramics can release inorganic biologically active ions and have a regulatory effect on the adhesion,proliferation and differentiation of related cells,and show a good effect of promoting repair.It is also possible to introduce functional elements such as Cu and Zn to endow the material antibacterial and immunoregulatory functions.Our subject is that using bioactive ceramics as the basis,adopting strategies such as combined antibacterial and immune antibacterial,preparing bioactive ceramic composites to achieve high-efficiency anti-drug-resistant bacterial infections and promote tissue repair effects.The main research contents and results are as follows:(1)The combined antibacterial strategy of heat and copper ions was used,and a polydopamine/copper-doped calcium silicate(PDA/Cu-CS)composite hydrogel was prepared for skin defects and infections.The hydrogel had good photothermal properties and could release copper ions.The focus was that the “hot ions effect” had synergy effect on inhibition of drug-resistant bacteria,with fast,high-efficiency and long-lasting antibacterial effects.At the same time,the complexation of polydopamine and copper ions(PDA/Cu)in the hydrogel system could enhance the photothermal,antibacterial and angiogenesis properties of the materials.An infectious skin wound model was used to evaluate the antibacterial and wound repair effects of the composite hydrogel in vivo.The hydrogel could quickly remove infection,promote skin tissue regeneration,accelerate the angiogenesis and collagen deposition.(2)Using immune antibacterial strategies,the Cu-Zn bi-layer nanofibrous membranes that affects the polarization of macrophages in different directions at different time periods was designed to treat implant-related infections(IRIs)and implant osseointegration disorders.Cu-Zn membranes were composed of cuprorivaite(CaCuSi₄O₁₀)loaded gelatin membrane(upper layer)and hardystonite(Ca2Zn Si2O7)loaded PCL membrane(lower layer).Cu-Zn membranes could release Cu²⁺ rapidly and in large quantities,and Zn²⁺ slowly and continuously.Cu²⁺ released from the membranes exerted direct antibacterial and anti-biofilm properties through generation of ROS.In early stage,membranes rapidly released Cu²⁺ more than Zn²⁺,stimulated macrophage polarization to M1 phenotype,induced pro-inflammatory immune responses,inhibited bacteria growth.In late stage,the concentration of Zn²⁺ was more than Cu²⁺,which promoted macrophage polarization to M2 phenotype,induced antiinflammatory effects,and accelerated the formation of new bone.The results of in vivo experiments also showed that the Cu-Zn bi-layer membranes could eliminate the infection of implants in the body,promote the regeneration of bone tissue at the bone defect site.(3)Adopting the strategy of combining “hot ions effect”,and endowing the material with targeted bacteria performance,the copper-doped mesoporous silica/polydopamine/glycol chitosan(MCS/PDA/GCS)composite nanoparticles was prepared.Nanoparticles possessed the function of bacteria targeting.When an infection occurred,the environment became acidic,and p H-sensitive nanoparticles could accumulate on the surface of the bacteria to achieve a targeting effect.The “targeted hot ions effect” of nanoparticles inhibited drug-resistant bacteria and biofilms.At the same time,nanoparticles affected the polarization of macrophages to M1 during mild heat,and enhanced the bacteria phagocytosis of macrophages.The material could eliminate drug-resistant bacterial infections on the wound surface under the strategy of combining the “targeted hot ions effect”.In addition,nanoparticles under mild heat could promote endothelial cell migration and angiogenesis,accelerate wound closure,and promote epithelial formation and angiogenesis.