Synthesis And Surface Modification Of Medical Poly (Phthalazinone Ether Ketone)

Bone implant materials are an important branch of biomaterials.The commonly used bone implant materials mainly include metal materials,ceramic materials and polymer materials.Polyaryletherketone materials have been widely used in orthopaedic surgery since the end of the last century due to less metal ion release,good biocompatibility,X-ray permeability and mechanical properties close to those of human bone.Conventional polyether ether ketone（PEEK）has poor solubility and dissolves only in H₂SO₄（98%）acid at room temperature due to its highly crystallinity,which limits the machinability of this materials.It is necessary to develop a medical polyaryletherketone material that can meet the needs and has excellent processing properties,low cost and independent intellectual property rights.At the same time,it is also a key research direction to enhance the low surface bioactivity of medical polyaryletherketone and to solve the problem of poor integration of the material with bone tissue.We had previously synthesised poly（phthalazinone ether ketone）（PPEK）using DHPZ and DFK by solution nucleophilic substitution stepwise polycondensation.In order to apply PPEK to the field of biomaterials,the effect of reaction conditions on the molecular weight and molecular weight distribution of the polymer was investigated in detail in this paper,including the initial monomer concentration,reaction temperature,excess molar ratio of monomers and reaction time.When the initial monomer concentration increased from 0.8 g/m L to 1.2 g/m L,the number average molecular weight of the polymer increased significantly,indicating that a higher initial monomer concentration was beneficial to the increase of the molecular weight of the polymer.When the temperature of the polymerisation reaction was 180℃,190℃and 200℃respectively,it was found that the higher the temperature,the faster the polymerisation reaction and the higher the molecular weight of the polymer obtained.When the polymerization reaction time was extended from 8 h to 14 h,the molecular weight of the product would go through a process of first increasing and then stabilizing.The effect of the excess molar ratio of monomer on the molecular weight and molecular weight distribution was also explored,so as to control the molecular weight of the product.In order to optimise the PPEK refining process,the effects of the type and proportion of solvents and the proportion of poor solvents on the refining effect of the polymer were investigated.The inorganic and organic impurity contents of the refined samples were characterised by ICP and GC-MS analysis respectively,which demonstrate the reduction of the residual organic impurity content in the samples to less than 0.1%and the total metal element content of concern to less than 100 ppm.The mechanical property,thermal property,solubility,rheological property and biological property of PPEK20000,PPEK40000and PPEK60000 were investigated in this paper.Hydroxylated PPEK（PPEK-OH）,aminated PPEK（PPEK-NH₂）and sulfonated PPEK（PPEK-SO₃H）were obtained by chemical modification base on PPEK.The adsorption of human fibronectin（Fn）on the surfaces of PPEK-OH,PPEK-NH₂ and PPEK-SO₃H samples was found to be increased by 20%,35%and 32%respectively compared with PPEK by QCM-D testing.The surface chemically modified PPEK samples were prepared by solution-spin-coating and marked as PPEK-F,PPEK-OH-F,PPEK-NH₂-F and PPEK-SO₃H-F.All modified samples showed improved osteoblast adherence compared to the unmodified samples.The results of the ALP activity test,alizarin red staining and PCR showed that the cells cultured on the surface of PPEK-NH₂-F and PPEK-SO₃H-F showed that a 2～3 fold increase in ALP activity at 7 and 14 days and a 2～3 fold increase in quantitative alizarin red staining data,and that the expression levels of the osteogenic differentiation-related genes Runx2,ALP and COL-I were significantly higher at 3,7 and 14 days.