Studies of Biodegradable and Injectable Composite Bone Filler Based on Polymer and Calcium Phosphate Ceramic Powder
Date Issued
2012
Date
2012
Author(s)
Wu, Chang-Chin
Abstract
While many different filler materials have been applied in vertebral augmentation procedures, none is perfect in all biomechanical and biological characteristics. To minimize possible shortages, we synthesized a new biodegradable, injectable and premixed composite made from poly(propylene fumarate) (PPF) and biphasic α-tricalcium phosphate (α-TCP)/hydroxyapatite (HAP) ceramics powder and evaluated the material properties of the compound in vitro. We mixed the PPF cross-linked by N-Vinyl pyrrolidinone and biphasic α-TCP/HAP powder in different ratios with benzoyl peroxide as an initiator.
The setting time and temperature were recorded, although they could be manipulated by differing the concentrations of hydroquinone and N-N-Dimethyl-p-Toluidine. Degradation, cytocompatibility, mechanical properties, and radio-opacity were analyzed after the composites were cured by a cylindrical shape. We also compared the study materials with polymethyl methacrylate (PMMA) and PPF with pure HAP particles. Results showed lower temperature during curing process (38-44oC), sufficient initial mechanical compression fracture strength (61.1±3.7MPa), and gradual degradation were observed in the newly developed bone filler. Radio-opacity in Hounsfield units was similar to PMMA as determined by computed tomography scan. Both pH value variation and cytotoxicity were within biological tolerable limits based on the biocompatibility tests.
Mixtures with 70% α-TCP/HAP powder were superior to other groups and were applied in vivo study.
To evaluate these cements in vivo, a porcine vertebral model was applied. Besides the before-mentioned 70% α-TCP/HAP/PPF mixture, 70% TtCP/DCP/PPF composite was also recruited in vivo for commercial availability and similar biphasic transformation properties after hydration to compare these two biodegradable cements with PMMA. Twelve miniature pigs had been enrolled in this study. Four cylindrical holes were drilled at the center of lateral cortex of vertebral bodies of lumbar spine with 5mm in diameter and 10mm in length through lateral retroperitoneal approach. The premixed cements were injected into the holes randomly and hardened in situ with setting time and highest setting temperature recorded. After 3months and 6months, the pigs were sacrificed. The retrieved spines specimens were scanned with X-ray and computed tomography. Samples were prepared for histological studies with/without de-calcification. The different appearances of solidified cements and the interaction zones between cement and bone were analyzed and compared.
Setting temperatures of PMMA were significantly higher than composite groups. There were two leakages of cement in spinal canals without significant neurological complication.
The differences were difficult to be identified by plain X-ray films and CT scans provided better resolutions for morphologic comparisons, volumetric measurement and quantified radiopacity among groups. Little volume, morphology and Hounsfield unit variation of PMMA is detected between 3 months’ and 6 months’ groups and implies inert nature of PMMA cement. Only 2 of 12 PMMA blocks were surrounded by radiolucent lines, and those lines were fibrous tissues in histology. While the remainder without radio-lucent lines were direct bone-PMMA contact. In contrast, irregular sclerotic ring along the cement blocks, significant decreases of cement volume and morphologic changes showed the degradability of both composite cements, despite the decreases of HU were not significant. More cement block laminations, radiolucent halos and vertebral deformities were observed in TtCP/DCP group, and this implied better degradability with obvious influences on surrounding host tissues by released products. Regarding control groups, the defects shrunk significantly with significant increase in Hounsfield units and this indicates good bone healing property of young porcine individuals.
New bone formation with substitution of cement were observed in histological specimens of both composite cements groups, but we are unable to quantify the differences between groups for sampling divergences, processing losses, staining errors and observer’s biases. Besides new bone formation and remodeling along outer surfaces of some composites blocks, however in some other blocks, abundant fibrous tissues surrounding, or even invading into blocks, was also observed in some vertebra. Radiological and histological changes were observed in all composite groups and these modifications were along diminished block boundaries. These suggested gradual substitution of decomposed composite by new bone formation, which could not be inspected around PMMA block.
In non-decalcified histology, results of PMMA group were more reliable but neither new bone formation nor composite substitution was identified along the PMMA blocks. When combining the results of gross, histological and radiographic finding, each radiologic finding corresponding to a specific histological illustration, such as radio-lucent line indicating histological fibrous tissue and sclerotic rings representing new bone formation with remodeling. Even though it is unable to make histological slices identical completely to CT scan slices, CT scanning could be a preliminary and easy way for evaluation of injectable bone cements in vertebral bodies.
This study indicated that these composites of PPF and biphasic CPCs powder are promising, premixed, injectable biodegradable bone fillers for these two composites possessing characteristics better than PMMA’s, but there are still some improvements should be done to increase reliability of the composite in the future.
Subjects
osteoporosis
vertebroplasty
poly(methylmethacrylate)
poly(propylene fumarate)
calcium phosphate
biodegradable cement
injectable bone cement
animal study
computed tomography
Type
thesis
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