| Objective:Implantable titanium and its alloy medical implants have been well developed and widely used in the clinic to replace damaged joint tissue and restore its function.Despite the good biocompatibility and mechanical properties of titanium and titanium alloys,implant failure due to excessive implant-bone bonding time and poor binding still occurs,suggesting that we need to modify the surface of the implant to improve the process to increase the success rate of the implant.Previous studies on the promotion of osseointegration through surface modification of implants have focused on the biological responses of certain bone-forming cells.With the deepening of the understanding of the concept of “osteoimmunomodulation”,the current basic consensus is: the inherent inflammatory response of the device after implantation into the host directly affects the metabolic balance of bone remodeling,which is the key factor in determining the prognosis of the implant.Therefore,it is necessary to study the effects of implant surface modification on the function of macrophage inflammatory secretion more thoroughly The surface characteristics of the implant should also coordinate the preparation of bone immunomodulatory materials,thereby promoting bone formation and facilitating osseointegration.Methods:1.Aspirin is coated in chitosan nanoparticles(ACS);then the prepared titanium discs are primed with PTL nanofilms;the negatively charged sodium hyaluronate and the positively charged type I collagen containing ACS are loaded by electrostatic adsorption sequentially.2.The prepared ACS and self-assembled type I collagen were observed by transmission electron microscopy(TEM).The morphology,properties and elemental composition of titanium discs,prepared Ti-PTL discs,Ti-PTL-HA discs and Ti-PTL-HA-(COL-ACS)discs were observed and analyzed by transmission electron microscopy(TEM),scanning electron microscopy(SEM),X-ray photoelectron spectroscopy(XPS)and contact angle measuring instrument.3.To analyse the release profile of ASA the titanium samples loaded with different volumes of aspirin in 1 to 7 days was determined in deionized water.The biocompatibility of the different samples was detected by rat bone marrow mesenchymal stem cells(BMSCs).According to the results,the optimal concentration was selected for subsequent experiments.4.The relevant inflammatory factors on the surface of different samples were detected by LPS-induced macrophages.In the different macrophage co-culture model,the early adhesion,migration and osteogenesis of BMSCs on different sample surfaces were observed.5.Titanium rods with different surface modifications were implanted into the rat femur defect model,and the implanted tissue attached with the titanium rod was taken out on the 3rd,7th,and 28 th days.Then,HE,VG and CD68+ staining treatment were carried out,and the initial anti-inflammatory ability and osteogenic ability of the sample were studied and analyzed.Results:1.The surface of ACS was smooth and well dispersed under TEM.The self-assembled type I collagen showed characteristic morphology.XPS and SEM results showed that the pure Ti discs with different modification steps were successfully loaded with PTL,HA and COL-ACS.The composite multilayer structure;the contact angle experiment not only confirmed that the successful loading of different modified films also confirmed that the material gradually modified and had good wettability.2.The sustained release capacity of samples loaded with different volumes of aspirin was proportional to the volume of drug added in 1 to 7 days.As for the proliferation and differentiation ability of BMSCs on different samples surfaces,the result suggest that lower dose group(3.0 ml)performed well in promoting cell proliferation and intracellular alkaline phosphatase activity,which was used in subsequent experiments.3.The results of LPS-induced macrophage inflammatory products on different material surfaces demonstrate that samples loaded with aspirin have the ability to inhibit the secretion of related inflammatory genes or proteins;results in the different models of conditioned media is proved that the multilayered samples with aspirin has better ability to promote BMSCs migration,adhesion,spreading and differentiation into bone than the blank titanium group.4.In the study of femur defects rat in vivo,the samples with composite multilayer structure loaded with aspirin showed that the bone defects loaded with aspirin were formed,the bone formation speed is fast and the inflammation reaction is light than the blank group.Conclusion:The PTL-primed aspirin-loading multifunctional structure prepared by this study can achieve the purpose of sustained release of aspirin,and has good biocompatibility,which is beneficial to the migration,spreading and osteogenic differentiation of BMSCs.It can resist the initial inflammatory reaction after implantation in vivo and has the ability to promote osseointegration. |
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