A Study Of Nano HA/PPS Composite As A Biomaterial To Repair Skull Defects

Skull defects frequently occur to the patients with diseases of brain injury, cerebrovascular accident and brain tumors and other complications after a surgery legacy. Skull defects can result in a series of neurological symptoms, causing severe headache, dizziness, fatigue, irritability, memory loss, depression, shock and a decline of noise tolerance. Every year, about 50,000 cases need surgical repairs for skull defects in China, thus demanding a big amount of cranial prosthesis implant material.Up to date,cranial prosthesis while undergoing a succession of several thousand years of history,so far,still not getting the science and biological properties of the material perfect combination of an ideal replacement implant material. Currently, titanium mesh is the most widely used clinical material,showing a number of obvious disadvantages and complications,such as: ① patients sensitive to hot and cold, local chronic pain, seroma more; ② after repair, influence patients underwent CT, MRI and other medical examination; ③ chronic cutting ulcers,stress-induced skull perforation repair failure; ④ temporal fossa zygomatic arch,box,and other irregular surfaces eyebrow skull parts repair appearance unsatisfactory cosmetic results; ⑤ custom cycle for a long time, the price is relatively expensive.This study is focusing on developing a new hard tissue biomaterial, especially polymer composites in terms of skull repair basic research and clinical application. First, we prepared a variety of chemical stability,excellent mechanical properties of the modified polyphenylene sulfide compounds, but these materials are poorly biocompatible. Meanwhile, the nano-hydroxyapatite has excellent biocompatibility and promotes osteoblast performance, but the mechanical strength, brittleness and fatigue resistance is insufficient and is limited in clinical applications of bone tissue implant. Therefore, we developed a novel material,which is made from polyphenylene sulfide nano-hydroxyapatite and two materials with a combination of their respective material properties. The new material is overall excellent, cheaper hard tissue implant materials for skull defects repair implant.Research methods:(1) The use of physical blending and direct complex Preparation of Nano HA / PPS composites. Comparison of two different formulations of the proportion of composite materials prepared by a water-absorbent, contact angle, simulated body fluid pH change detection study nano-characterization and mechanical properties of HA-PPS composites.(2) According to the national standard GB / T standard biological evaluation of medical devices by the acute toxicity test, cytotoxicity test, hemolysis experiments evaluate new technology to produce nano-HA / PPS composite biocompatibility.(3) The nano HA / PPS and osteoblasts in vitro co-culture, to determine the effect of nano HA / PPS on osteoblast proliferation and differentiation. Establishing skull defect animal model implanted nano-HA/PPS composites by X ray imaging, histopathology test, osteogenic activity related gene PCR analysis, further evaluation of nano-HA / PPS composites in the biological activity in vitro and in vivo and Repair bone skull defects after integration.Results:1. Characterization and Mechanical Properties of Nano HA / PPS composites(1) Direct Composite particle size uniformity as good as micron, hydroxyapatite uniformly filled polyphenylene sulfide matrix.(2) composite hydrophilic good, hydroxyapatite added polyphenylene sulfide can effectively reduce the surface contact angle,contact angle PPS is 93.22 °, direct composite(3:7) Material of contact angle is 25.83,the contact angle of direct composite(4:6) material is 33.33 °, the contact angle decreased, indicating a high hydrophilic material. In the material water absorption tests also found that the composite material hydrophilic improved test results consistent with the contact angle.(3) increase the stiffness of the composite material. In the flexural strength test, the flexural strength of the composite material 93.288 MPa, flexural modulus 5159.78 MPa, polyphenylene sulfide pure bending strength 103.68 MPa, flexural modulus 2789.5MPa. In the tensile test, the tensile strength of 45.948 MPa, tensile modulus 2696.95 MPa, pure PPS tensile strength 60.974 MPa, tensile modulus 1740.19 MPa. Thus, adding hydroxyapatite in PPS can improve the stiffness of the material.(4) changes in p H caused by immersion in SBF,p H range is caused by direct composite 7.4-7.51,pH range caused by physical blending composites between 7.4-7.72 direct than physical blending composites Composite materials are more stable, more suitable for implantation in the human body.2. Biocompatibility of Nano-HA / PPS composites(1) nano-HA / PPS composite extract celiac gross observation and histopathology were not there poisoning rats after injection;(2) Cytotoxicity was found in rat L929 fibroblast cells were co-cultured cell morphology evaluation test of nano-HA / PPS composites,non-toxic, CCK-8 assay cell relative growth rate(RGR) index has reached toxic levels 0 evaluate cytotoxicity.(3) test confirmed hemolytic nano-HA/PPS composites blood compatibility, hemolysis rate was 1.66%.Biocompatible nano-HA / PPS composites is good, and its acute toxicity tests, in vitro cytotoxicity, blood compatibility test results are complex countries to develop biological implant material safety evaluation standards, excellent biocompatibility.3. Evaluation of the biological activity of nano-HA / PPS composites(1) MG-63 cells in the nano-HA / PPS composite surface grew well, with better than pure PPS cell adhesion;(2) Nano-HA / PPS composites can promote the proliferation of MG-6 cells, more pronounced effect than pure PPS;(3) Nano-HA / PPS composites can improve the MG-63 cells into bone-specific protein expression and MG-63 cells into osteoblasts;(4) Nano-HA / PPS composites skull defects after implantation of bone tissue healing well; a significant increase as an important marker of bone-related genes, such as: ALP, Colα1(I),IGF-1,OC,TGF- of mRNA expression.Conclusion:Nano-HA prepared by direct complex legal / PPS composites has stable physical properties and significantly improve hydrophilic properties, flexural strength and tensile strength as compared to pure PPS. Biocompatibility evaluation have shown nano-HA / PPS composite safe poison, good biocompatibility. In vitro results indicate the biomaterial can promote osteoblast proliferation and increase expression of specific proteins in the body after implantation into bone healing well. The increased osteogenic marker gene expression may be associated with better performance biomaterials engineering, as a potential alternative materials to repair the skull.