Novel Porous Surface Modified Bioactive Bone Cement For Use In Vertebroplasty

BackgroundThere are about1.81million cases of osteoporotic vertebral fracture eachyear in our country. Vertebroplasty is commonly used for osteoporotic vertebralfracture, during which polymethylmethacrylate bone cement polymerizes andhardens upon injection into the vertebral body and stabilizes the fracture.However, there are several disadvantages of the bone cement: nonbiodegradable,nonosteogenic activity and high elastic modulus. The ideal bone cements for usein vertebroplasty is expected to be biodegradable, have osteogenic activity andlow elastic modulus. Bioglass, a biological material developed in recent years,have good biocompatibility and bioactivity. Chitosan, a natural polymer, hasgood biocompatibility. A new bone cement can be developed if chitosanparticles and bioglass particles were incorporated into polymethylmethacrylatebone cement. The resulting bone cement would be biodegradable and show bioactivity.ObjectivesThe aim of this study is to develop a new injectable bone cement for use inverteoplasty which is biodegradable, possess osteogenic activity and has lowelastic modulus.Materials and Methods1. The new bone cement was composed of bioactive glass particles, chitosanparticles and polymethyl methacrylate powders.45S5bioactive glass was milledinto about10μm particles in diameter. Average molecular weight of chitosanwas300KD, and degree of acetylation is greater than90%.Polymethylmethacrylate bone cement came from simplex P bone cement. Therewere three different groups in this experiment according to the components ofsolid phase. BC40group was composed of40wt%bioglass particles,50wt%ofpolymethyl methacrylate powders and10wt%chitosan particles. BC50groupwas composed of50wt%bioglass particles,40wt%of polymethyl methacrylatepowders and10wt%chitosan particles. As control group, PMMA was composedof100wt%of polymethyl methacrylate powders. The liquid phase waspurchased from the Stryker Company of US. The composition was97.5wt%ofmethyl methacrylate,2.5wt%of dimethyl-p-toluidine and7.5mg/mLhydroquinone. After curing, each group of bone cement was examined withscanning electron microscope to observe the surface morphology and determinethe distribution of the components.2. Bone cement samples were soaked in phosphate buffer solution for4 weeks. Samples before and after1week,2weeks and4weeks degradation wastaken out and dried, and then compressive strength and elastic modulus wasexamined. After immersion in simulated body fluid for21days, bone cementsamples of BC40group were tested for in vitro biological activity with scanningelectron microscopy, energy dispersive spectrometer and X-ray diffraction.3. We used PMMA as control. MC3T3-E1mouse osteoblast cell was used toevaluate cytotoxity, cell adhension, cell proliferation and cell differentiation.4. After bone cement samples were implanted in rabbit femoral condylebone defect model for12weeks, samples were examined using micro-CT andhistological analysis to analyze bone formation and invivo degradation ofmaterials.Results1. Results of scanning electron microscopy revealed that chitosan particlesand bioactive glass particles uniformly distributed in the PMMA matrix in BC40and BC50group while PMMA group presented a smooth surface structure.2. The setting time of BC40group, BC50group and PMMA group were12.7±0.3min,14.2±0.3min and8.6±0.3min respectively. The setting time ofBC40group and BC50group were longer than that of PMMA group. Thecompressive strength of BC40group and BC50group after4weeks degradationdecreased to72.71±3.53Mpa and63.60±4.92Mpa, while the compressivestrength of the PMMA group did not decreased. The elastic modulus of BC40group and BC50group deceased to1.54±0.04Gpa and1.49±0.05Gparespectvely, which were lower than that of PMMA group. After4weeks of degradation in PBS, the surface of BC40formed irregular macroporores withabout100μm in diameter. The results of SEM showed apatite crystallizationwas observed on surface of BC40after immersed in SBF for7days. The EDSanalysis revealed that silicon peak dispeared and the peak of calcium andphosphorus significantly increased after soaked for7days. X-ray diffractionanalysis showed that a peak was present at the diffraction angle32°.3. There were no significant difference between cytotoxity of PMMA groupand BC40group. The cell number of osteoblasts attached on PMMA groupsample after3h culture was lower than that on BC40group sample. Bundles ofcells were not fully extended on PMMA group sample, while expandedcytoskeleton is clearly visible on BC40group sample. Cell number on BC40group sample was higher than that on PMMA group sample after proliferationfor4days. The level of alkaline phosphatase on BC40group sample was higherthan that on PMMA group sample after cultured for7days and14days inosteogenic differentiation.4. Micro-CT showed that new bone ingrowth was observed in BC40, whileno bone ingrowth in PMMA. The new bone volume of BC40is higher than thatof PMMA. A large part of material was degraded at the edge of BC40andporous surface structure was observed. However, no degradation was observedin PMMA. The residual material volume ratio of BC40was lower than that ofPMMA. Results of the histological analysis indicated that chemical bondingformed between BC40and host bone, and new bone ingrowth was observed. Alayer of fibrous tissue existed between the PMMA and host bone. ConclusionsBone cement BC40is partially biodegradable and has good bioactivity,sufficient strength and low elastic modulus. Our findings suggested a newbioactive bone cement for use in vertebroplasty.