Study On UHMWPE Loaded With Alendronate Sodium

Ultra-high molecular weight polyethylene (UHMWPE) has been used as the component material for total hip joint replacement prostheses for approximate five decades. However UHMWPE wear debris generated from the prostheses could stimulate osteolysis, which is thought to be the major factor that induces the loosening of prosthesis. Considerable researches have been focused on prevention of peri-implant osteolysis. The main approaches include reducing the generation of wear debris in terms of tribology and material science, and preventing osteolysis pharmacologically. Our previous study has developed UHMWPE loaded with 17β-estradiol with the acceptable mechanical and tribological properties. However, the use of 17β-estradiol may be limited by gender because it is a kind of estrogen hormone, which is usually used to treat the osteoporosis of postmenopausal women. Furthermore, the distribution of drug in UHMWPE is needed to be investigated. In this study, UHMWPE loaded with alendronate sodium (UHMWPE-ALN) was processed by the solvent evaporation and hot press methods. Alendronate sodium (ALN) is an aminobisphosphonate which possesses the inhibitory effect on osteolysis and good thermal stability. It is expected that a stable release of drug could be achieved with the generation of wear debris after implanted. Therefore, UHMWPE-ALN may be used to potential component material to prevent the wear debris-induced osteolysis and increase the longevity of joint replacement prosthesis.The functional group, density, surface energy, drug distribution, crystal structure, crystallinity and mechanical properties of UHMWPE-ALN were characterized by fourier transform infrared spectroscopy (FT-IR), the drain away liquid method, contact angle measurement, time-of-flight secondary ion mass spectrometry analysis (ToF-SIMS), X ray diffraction (XRD), differential scanning calorimetry (DSC) analysis, small punch test and micro-hardness test, compared with UHMWPE in this study respectively. In this study, two methods to generate UHMWPE-ALN wear debris were explored and compared, and the in vitro drug release of UHMWPE-ALN wear debris was investigated. An inverted cell culturing apparatus and procedures were used when UHMWPE-ALN wear debris was co-cultured with osteoblast cells and macrophage cells respectively in vitro to study the biological reaction to the wear debris. Cell morphology was observed by optical microscope. Cell proliferation of osteoblast cells and macrophage cells were investigated by MTT assay. The differentiation of osteoblast cells was studied by determining the activity of alkaline phosphatase (ALP), and the expression of pro-osteolytic cytokines (interleukin-6, IL-6 and tumor necrosis factor-a, TNF-a) were investigated by enzyme-linked immunosorbnent assay (ELISA).FTIR analysis demonstrated that hot press had no effect on the chemical structure of ALN, the characteristic functional groups (peaks at 3500 cm-1-3400 cm-1 owing to OH and NH2 stretching vibration, peaks at 1640 cm-1 owing to NH2 bending vibration, peaks at 1050 cm-1 and 1020 cm-1 owing to P=O stretching vibration, peaks at 926 cm-1 owing to OH bending vibration) all appeared in UHMWPE-ALN and no new addition peak except those attributed to pure UHMWPE and ALN was observed. Since ALN possesses the characteristic elements such as N, P, O and Na, ToF-SIMS analysis showed that ALN did not agglomerate in UHMWPE-ALN by investigating the distribution of second ions (Na+, C3H8N+, PO3- and PO3H-),. The results of the density, surface energy and crystal structure indicated that ALN did not affect the mechanical properties at the present content of ALN. Although the crystallinity degree of UHMWPE-ALN decreased, the results of small punch test and hardness test demonstrated that there was no statistically significant difference in the mechanical properties. As reported in other studies, positive, statistically significant correlations were observed between the wear resistant of UHMWPE and the initial peak load, ultimate load from the small punch test. The relation of wear mass loss of the UHMWPE acetabular cup and the micro-hardness followed a negative power law. Thus, it was inferred that ALN had no effect on wear resistance of UHMWPE-ALN at the present content.The results of the in vitro drug release showed that the release procedure could be divided into three stages:burst release, quick release and stable release. The percentage of drug released from UHMWPE-ALN wear debris was about 34% when the release finally come to the third stage. The results of cell culture indicated that ALN in the experimental concentration (10-8-10-6 mol/L) could improve the proliferation and differentiation of osteoblast cells, inhibit the proliferation and secretion of pro-osteolytic cytokines (IL-6 and TNF-a) of macrophage cells. These results indicated that ALN released from UHMWPE-ALN wear debris could enhance the osteogenesis but inhibit the osteolysis.The present study demonstrated that UHMWPE-ALN processed by hot press possessed the same material properties similar to those of UHMWPE, and would be potentially used to prevent the wear debris-induced osteolysis by affecting on osteoblast cells and macrophage cells in total hip replacements.