Construction Of Biofunctional Titanium Surface And Its Biological Responses Based On The Modification Of OGP

Titanium and its alloys have been commonly used in the orthopedics field because of their corrosion resistance,light weight,good mechanical properties,and biocompatibility.However,during the repairing process for hard tissue,the integration between titanium implant and its surrounding bone was slowly due to the inherent bio-inertness of the titanium implant surfac,which even causes the loosening and failure in the later stage.The main reasons are as follows:(1)bacteria infection around the titanium implant results in the adhesion of bacteria and proliferate in large amounts to form biofilms on the implant surface,which can inhibitthe combination of the implant and the surrounding bone tissue;(2)long-term inflammation caused by titanium implantation promotes the activation of osteoclasts,leading to the imbalance of bone metabolism around the implant and delaying osseointegration.Therefore,the functional modification of titanium surface to promote bone-implant interface seamless formation is the focus of current research.Growth factor therapy is considered to be a promising method for the promotion of new bone formation.It plays an important role in antibacterial and the regulation of cell behavior,including cell recruitment,migration,adhesion,proliferation and differentiation.In view of this,in this work,the osteogenic growth factor(Osteogenic growth peptide,OGP)was modified with two functional small molecules respectively.Then,the modified OGP was fixed covalently on the titanium surface to prepare two kinds of biofunctionalized titanium substrate with the function of promoting osseointegration as well as antibacterial or regulating bone balance.The main research contents and conclusions are as follows:1.Modification of osteogenic growth peptide which inhibits bacterial infection and its application on titanium surfaceTo improve osseointegration and antibiosis,a novel antimicrobial osteogenic growth peptide OGP-CIP was synthesized by conjugating osteogenic growth peptide(OGP)and ciprofloxacin(CIP)firstly.Then OGP-CIP was grafted onto the Ti substrate surfaces by a silanization-based amide reaction.Thereafter,the capabilities of modified Ti substrates on osseointegration and antibiosis were measured with material characterization,cell experiments and antimicrobial activity in vitro.The results proved that OGP-CIP was successfully synthesized and immobilized onto Ti substrate surfaces.Moreover,the antimicrobial peptide-modified surfaces could promote the spreading,proliferation and differentiation of osteoblasts when compared with unmodified Ti substrates.Meanwhile,bacteria studies(Staphylococcus aureus and Escherichia coli)proved that the antibacterial property of antimicrobial peptide functionalized Ti implant was improved obviously.2.Modification of osteogenic growth peptide which regulates the balance of bone metabolism and its application on titanium surfaceTo modify titanium(Ti)substrates and accordingly regulate the balance between osteoclast activation and osteoblast differentiation,a multifunctional peptide OGP-NAC was synthesized via conjugating osteogenic growth peptide(OGP)with N-acetylcysteine(NAC).Then,the synthesized peptide OGP-NAC was employed to functionalize Ti substrates.The responses of both osteoblasts and osteoclasts were investigated in vitro.The results proved that OGP-NAC was successfully synthesized and immobilized onto Ti substrate surfaces.Thereafter,studies on introducing RAW 264.7 cells to osteoclasts demonstrated that the OGP-NAC modified Ti surface could inhibit the formation of polykaryotic cells,the secretion of TRAP and the expression of osteoclast related genes,consequently,inhibit the formation and activation of osteoclasts.Meanwhile,the modified surface can significantly promote the spreading,proliferation and differentiation of osteoblasts,as well as up-regulate the expression of osteogenic-related genes.