| Load-bearing orthopedic implants,like artificial knee implants,artificial hip implants,and intervertebral cages,which are applied to the limbs and spine.The load-bearing orthopedic implants not only provide structure for filling the bone defects,but also bear mechanical forces during movement.Hence,these implants must have good mechanical properties which match the natural bone.At present,the materials used for load-bearing orthopedic implants in clinical orthopedics mainly include metal materials represented by titanium alloys,and special engineering plastic materials represented by PEEK.Titanium alloys have a lower elastic modulus(100-110 GPa)and better biocompatibility than most other metallic alloys used in orthopedic clinical practice.PEEK has an elastic modulus of 3.5–3.9 GPa,which is closer to that of natural bone(10-30 GPa).Moreover,mechanical strength of the special engineering plastic materials can be further enhanced by doping other materials.However,the surface of both Titanium alloys and PEEK is biologically inert,and they fail to achieve strong and direct interaction between the bone and the surface(osseointegration).The weak osseointegration performance of the surface will have negative effect on the rapid osteogenesis and the long-term service life for the implant.With the advancement of public health and medical care,the average life expectancy of human beings increased.At the same time,the age of joint replacement for becoming gradually younger.This situation would result in shorter service life for the load-bearing orthopedic implants with poor osseointegration than the patient's life expectancy,which would inevitably lead to revision surgery.However,the physical health and bone conditions of patients who need revision surgery would become worse than those of the initial surgery,which brings great challenge to the revision operation.The risks of revision surgery,the pain suffered by patients,and the financial burden put forward urgent requirements for improving the osseointegration performance of load-bearing bone implants.Surface modification of implants is a promising approach to overcome the bioinertness of the surface,leading to improved osseointegration.On the one hand,it can promote osteogenic differentiation and bone development by adjusting the physical and chemical signals on the surface of the implant;On the other hand,surface modification can be used to adjust the microenvironment around the implant,which could suppress negative factors that are not conducive to tissue repair,and enhance positive factors that promote bone regeneration.Tantalum and tantalum-based composite materials have good biological properties and corrosion resistance,and their osteogenic activity can be improved by doping other elements.Therefore,the tantalum-based coating on the surface of load-bearing implants has received a lot of attention.In this study,we used magnetron sputtering technology to prepare tantalum-based coatings on the surface of the load-bearing bone implant material,and tried to achieve a better osseointegration effect by improving the biological activity of the surface and adjusting the local microenvironment surrounding the implant.The research content mainly includes the following two parts:1.Preparation of TaCN coating on the surface of titanium alloy implants to achieve good osseointegration repair by recruiting bone growth factors in the local microenvironment.This part is composed of chapters 2-3.We obtained TaC and TaCN coatings on titanium alloy samples by magnetron sputtering technology,and the pure TC4 substrate was set as control.The results of AFM found that the morphology and roughness of TaC and TaCN coatings are similar,and they were slightly lower than that of TC4,which indicate that the coatings have little effect on the surface morphology of the sample.The water contact angle test indicates that the two coating materials of TaC and TaCN were hydrophilic.The in vitro studies on cell adhesion,cell viability and cell proliferation found that the biocompatibility of TaC and TaCN groups was better than that of TC4.However,the effects of the two coating materials on the osteogenic differentiation of BMSCs were quite different:Compared with the TaC and TC4 groups,TaCN could promote the secretion of alkaline phosphatase.TaCN could up-regulate the expression for BMP-2,Runx-2,and OPN at 4 and 7 days.While the expression of Runx-2 for TaC group was lower than the TaCN group at 4 days.Moreover,the expression of BMP-2,Runx-2,and OPN for TaC was lower than the TaCN group at 7 days.In summary,both TaC and TaCN coatings have good biocompatibility,and TaCN coating can significantly promote the osteogenic differentiation of BMSCs.To explore the related mechanism,we further analyzed the physical and chemical properties of the coatings which soak in the SBF for 72 h,it is found that the surface of the TaCN coating exhibits a negatively charged surface with abundant functional groups(OH-).In vitro protein adhesion experiments and in vivo protein array analysis provide evidence that the positively charged host BGFs and protein could be enriched on the surface of implants to improve bone healing.Under the forementioned cascade effect,TaCN shows superior performance of osseointegration in vivo,in which the amount of newly formed bone around the TaCN implant is nearly 2-folds higher than that around the Ti6Al4 V implant,and the bone tissues around the implant are in direct contact with the TaCN surface.The excellent osseointegration of TaCN film demonstrates that it can be a potential method to enhance osseointegration for artificial bone tissue engineering.More importantly,this work provides an innovative and clinically transformable strategy to improve bone healing via mobilizing host BGFs to the site of repair.2.Preparation of 3D printed porous PEI-TCP to improve bone ingrowth,and preparation TaN coating on the surface of the scaffolds to improve biocompatibility and anti-inflammatory effects,which in turn promote osseointegration through the coordination of osteogenesis and anti-inflammatory effects.This part is composed of chapters 4-5.Polyetherimide(PEI)was selected for the study of 3D printed bone scaffold.PEI is a special engineering plastic whose cost is lower than PEEK,and it is easier to process than PEEK.Its mechanical properties are close to PEEK.In this part of the work,PEI and PEI-TCP(contains 10 wt.%?-TCP)scaffolds were fabricated via FDM technology,and then 10 wt.% ?-TCP was doped into the PEI material,and then PEI-TaN and PEI-TCP-TaN scaffolds were obtained by depositing TaN coating on the surface of PEI and PEI-TCP scaffolds by magnetron sputtering technology.The mechanical test and in vitro experiment shown that the incorporation of ?-TCP and TaN can improve the mechanical properties and biocompatibility of the material.However,the PEI-TCP has no obvious effect on cell proliferation.The two groups which doped with ?-TCP(PEI-TCP,PEI-TCP-TaN)could improve the secretion alkaline phosphatase,enhance the mineralization of extracellular matrix,and up-regulate the expression of osteogenic related genes(BMP-2,Runx-2,OCN,OPN).However,there was little difference in osteogenic activity before and after application of TaN coating.We speculate that TaN has no obvious osteogenesis effect,and its good biocompatibility cascade that promotes osteogenic differentiation.The in vitro inflammatory experiments show that the incorporation of ?-TCP enhanced the inflammatory response.PEI-TCP could up-regulate the expression pro-inflammatory genes,such as CD11c?iNOS?TNF-?,while PEI-TaN and PEI-TCP-TaN could down-regulate the expression of these genes.This result showed that the TaN coating on the surface of the scaffolds successfully inhibited the inflammatory response.Finally,animal experiments provided evidence that the PEI-TCP-TaN coating can significantly enhance bone ingrowth and regeneration.The anti-inflammatory effect of TaN and the osteogenic effect of?-TCP can synergistically promote good osseointegration of the implants.This study demonstrates that PEI-TCP-TaN is a potentially promising orthopedic implant,and it also provides a feasible strategy for coordinating the inflammatory response and osteogenic differentiation.More importantly,this is a beneficial attempt to combine surface treatment with the structure of 3D printed porous scaffolds for better osseointegration. |
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