Preparation And Study Of Titanium Implants With Immunomodulation And Osteointegration Properties

As an effective clinical bone replacement / implant material,titanium and its alloy have similar mechanical properties and excellent mechanical properties with natural bone.However,due to the biological inertness of titanium,it is difficult to form an effective osseointegration around the implants and easy to cause inflammatory responses.Therefore,it has become an important research direction to modify the surface of the titanium materials to improve the osseointegration ability of titanium surfaces.Herein,in this study,we immobilized the LL-37 peptide loaded silk fibroin nanoparticles on titanium surfaces by silane coupling and glutaraldehyde chemical grafting methods.The synergistic biological regulation of mesenchymal stem cells and macrophages improved titanium osseintegration.The main research contents and conclusions are listed as follows:1.Synthesis and characterization of peptide LL-37 loaded silk fibroin nanoparticles on titanium surfacesSilk fibroin nanoparticles loaded with peptide LL-37 were fixed on the surface of titanium by silane coupling and glutaraldehyde chemical grafting.SEM,AFM,XRD,contact angle test and peptide release experiments showed that the Ti-SF / LL-37 group had been successfully fabricated and peptide LL-37 was successfully loaded.Peptide LL-37 was released quickly in the initial hours and slowed down in the following days.The actual cumulative releases amounts of the Ti-SF / LL-37 group was 1.49?g.2.The in vitro studiesIn this section,mesenchymal stem cells and macrophages were employed to explore the cell recruitment,early adhesion,proliferation,and paracrine-effets.MTT,ALP,alive / skeletal staining,qRT-PCR,immunofluorescence staining,Transwell and other in vitro cell experiments proved that the Ti-SF / LL-37 group can recruit mesenchymal stem cells and macrophages and it had no significant cytotoxicity.Moreover,it was beneficial for cell growth and spreading.At the same time,it can also regulate the biological communications between the two cells to regulate inflammatory responses and promote osteointegration.3.The in vivo studiesIn this section,a femur-defect model of rats was constructed and the sample s were implanted.The endogenous MSCs and macrophages recruitment,inflamma tory response-and new bone formation were studied by H&E staining,Masson's staining,and immunohistochemistry staining.The results showed that the Ti-SF/L L-37 group can curb thepro-inflammatory response,improve anti-inflammatory re sponse,and promote the osteointegration.In this study,the Ti-SF/ LL-37 group was proved to be able to recruit mese nchymal stem cells and macrophages and regulate their biological functions.Mes enchymal stem cells could be attracted to migrate to the implantation sites.The paracrine of mesenchymal stem cells can regulate the phenotype switch of macro phages(from pro-inflammatory phenotype to anti-inflammatory phenotype),Then the anti-inflammatory response was improved and a better osteointegration was a chieved.This study,presented a great of significance to regulate inflammatory re sponses and improve osteointegration of titanium implants.