Tissue Engineering Composite Bone Cement for Reinforcing Osteoporotic Bone   Matthew A Wettergreen, Antonios G Mikos,  Mic...
Background <ul><li>Vertebroplasty as prophylactic treatment </li></ul><ul><li>Use of bone cements in vertebroplasty </li><...
Incorporation of Solid Phase <ul><li>Previous studies attempted to increase mechanical properties </li></ul><ul><ul><li>UH...
Hypothesis <ul><li>Hypothesis  – The permeability of a solid can be altered by modifying the surface to volume ratio of th...
Objective <ul><li>Investigate effect of surface to volume ratio of a porogen on permeability </li></ul><ul><li>Explore fea...
Methodology <ul><li>Generate and build micro-architecture </li></ul><ul><li>Create and evaluate porous scaffolds </li></ul...
<ul><li>Removal of solid similar to porogen process to create porosity in scaffolds </li></ul><ul><li>Size of micro-archit...
Generation of Y-Shapes 0.98 0.39 0.29 0.33 0.45 Avg. Volume = 0.221 mm 3 Avg. Volume = 0.221 mm 3 Bounding box =  1.0mm x ...
Building of 3-D architecture Fused Deposition Modeling Material Reservoir Piezo 1 mm y z
Creation of Porous Scaffolds <ul><li>50, 60, 70% porosity  by volume  created in acrylic resin </li></ul><ul><ul><li>Major...
Evaluation of Permeability <ul><li>Permeability is material property; fluid independent </li></ul><ul><li>Pore size is lar...
Permeability Results <ul><li>Higher surface to volume ratio resulted in higher permeability </li></ul><ul><li>Trabecular b...
Evaluation with QCT <ul><li>Samples scanned with Scanco  μ CT80 </li></ul><ul><li>Porosity evaluated by thresholding by de...
Error in build processes <ul><li>Print width range 90-115  μ m </li></ul><ul><li>Surface to volume ratio higher than initi...
SEM of Scaffolds <ul><li>Imprint of solubilized face shown </li></ul><ul><li>Build imperfections negligible </li></ul>
Results <ul><li>Higher surface/volume ratio contributes to increase in permeability </li></ul><ul><li>Interconnectedness p...
Results <ul><li>Global shape can be built using RP processes </li></ul><ul><ul><li>Build error may limit complex architect...
Future Directions <ul><li>Determine a dependence of architecture on pore size resulting in solid </li></ul><ul><li>FEA of ...
Acknowledgements <ul><li>Computational and Experimental Biomechanics Laboratory </li></ul><ul><li>Mikos Research Group </l...
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Tissue Engineered Composite Bone Cement For Reinforcing Osteoporotic Bone, 4/2003

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ABSTRACT
Tissue Engineered Composite Bone Cement For Reinforcing Osteoporotic Bone
Matthew Wettergreen, Michael A.K. Liebschner
Department of Bioengineering, Rice University, Houston, TX

INTRODUCTION: Injectable materials for use in vertebroblasty and kyphoplasty have been augmented with micro- or nano- sized particles to increase the overall mechanical strength of the composite material. These studies have focused solely on the improvement of the mechanical properties through the adjustment of geometry, architecture, and degradation profile of the material. The goal of the current study was the generation of a porous material, with a controlled rate of degradation, which can be used for injection purposes.

MATERIALS AND METHODS: By focusing on the engineering of an interconnected pore structure, a high surface area to volume ratio can be created, increasing the strength of the material while maintaining porosity. A novel injectable bone cement is created using a Calcium Phosphate slurry with solid phase polypropylene fumarate (PPF) particulates of engineered architecture. The PPF is formed into macrosize (~750um) two-dimensional star-like shapes using rapid prototyping technology and molding processes. The star shape is designed to seal the spaces between adjacent trabeculae, which have a spacing of approximately 1mm. Plugging of the inter-trabecular spacing should aid in the containment of the liquid bone cement during injection, preventing the common problem of overfilling.

RESULTS AND CONCLUSION: The optimal volume percent and +/-10% volume percent of PPF is introduced into the viscous material to create the injectable composite. The three formulations are then injected into cylindrical volumes for testing purposes. After curing, the samples are scanned on a µCT 80 (Scanco Medical, Basserdorf, Switzerland) with a resolution of 10um. Incorporation of a contrast agent will allow the visualization of each phase of the composite material using µCT. The scans will be used to evaluate the interconnected void spaces formed when the PPF degrades. A degradation study is performed to evaluate the degradation of the PPF micro-particles. Degraded samples will be mechanically tested to evaluate whether degradation of the microparticles reduces the mechanical strength of the cements to levels insufficient for usage in vertebroblasty and kyphoplasty. By using a composite material consisting of a liquid element phase, an ordered pore structure can be generated. The cured material may promote bone growth and could ultimately improve the biomechanical quality of the regenerated trabecular bone in a vertebral body after treatment. The incorporation of geometric shapes and regulated architecture into liquid injectable materials could be used in vertebroblasty and kyphoplasty for reinforcement or bone fracture repair.

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Tissue Engineered Composite Bone Cement For Reinforcing Osteoporotic Bone, 4/2003

  1. 1. Tissue Engineering Composite Bone Cement for Reinforcing Osteoporotic Bone Matthew A Wettergreen, Antonios G Mikos, Michael AK Liebschner
  2. 2. Background <ul><li>Vertebroplasty as prophylactic treatment </li></ul><ul><li>Use of bone cements in vertebroplasty </li></ul><ul><li>Positive effects </li></ul><ul><ul><li>Restoration of strength </li></ul></ul><ul><li>Negative effects </li></ul><ul><ul><li>Increased stiffness </li></ul></ul><ul><ul><li>Non-osteointegrative </li></ul></ul>
  3. 3. Incorporation of Solid Phase <ul><li>Previous studies attempted to increase mechanical properties </li></ul><ul><ul><li>UHMWPE + MMA, Yang et al., 1997 </li></ul></ul><ul><ul><li>Titanium + PMMA, Topoleski, 1995 </li></ul></ul><ul><li>Paradigm shift - Solid phase for therapeutic purposes </li></ul><ul><ul><li>Compensate for decreased strength of material </li></ul></ul><ul><li>Remove solid to create porous structure </li></ul><ul><li>Promote permeability to aid in regrowth </li></ul>
  4. 4. Hypothesis <ul><li>Hypothesis – The permeability of a solid can be altered by modifying the surface to volume ratio of the porogen used in that solid. </li></ul>
  5. 5. Objective <ul><li>Investigate effect of surface to volume ratio of a porogen on permeability </li></ul><ul><li>Explore feasibility of using rapid prototyping as an evaluation tool for porogen architecture fabrication </li></ul>
  6. 6. Methodology <ul><li>Generate and build micro-architecture </li></ul><ul><li>Create and evaluate porous scaffolds </li></ul><ul><ul><li>Porosity </li></ul></ul><ul><ul><li>Permeability </li></ul></ul><ul><li>Evaluate rapid prototyping processes </li></ul>
  7. 7. <ul><li>Removal of solid similar to porogen process to create porosity in scaffolds </li></ul><ul><li>Size of micro-architecture comparable to NaCl particles </li></ul><ul><li>Bounding box of micro-architecture small enough for use in syringe </li></ul><ul><li>High surface to volume ratio in comparison to control </li></ul>Micro-Architecture Design Demands
  8. 8. Generation of Y-Shapes 0.98 0.39 0.29 0.33 0.45 Avg. Volume = 0.221 mm 3 Avg. Volume = 0.221 mm 3 Bounding box = 1.0mm x 1.5mm Surface Area = 2.895 mm 2 Surface Area = 2.196 mm 2 Bounding box = 0.60mm x 0.60mm All dimensions in mm 0.50 - 0.71
  9. 9. Building of 3-D architecture Fused Deposition Modeling Material Reservoir Piezo 1 mm y z
  10. 10. Creation of Porous Scaffolds <ul><li>50, 60, 70% porosity by volume created in acrylic resin </li></ul><ul><ul><li>Majority of studies utilize weight percentage </li></ul></ul><ul><li>Scaffolds formed in GPC vials </li></ul><ul><ul><li>Final scaffold dimensions d=6mm, h=12mm </li></ul></ul><ul><li>NaCl removed with H 2 O, Y7 removed with EtOH </li></ul><ul><ul><li>Scaffolds submerged in H 2 O prior to evaluation </li></ul></ul>
  11. 11. Evaluation of Permeability <ul><li>Permeability is material property; fluid independent </li></ul><ul><li>Pore size is large determinant of permeability </li></ul>Q A = (k/ μ )( Δ P/ Δ L) Q A = Flow Rate (m 3 /s) μ = Dynamic Viscosity (Ns/m 2 ) Δ P = Pressure (N/m 2 ) L = Scaffold Length (m) k = Intrinsic Permeability (m 2 ) Darcy’s Law of permeability
  12. 12. Permeability Results <ul><li>Higher surface to volume ratio resulted in higher permeability </li></ul><ul><li>Trabecular bone permeability between 7E -6 – 8E -5 for given porosity values </li></ul>1.71E -04 3 50% Vol. Y7 Scaffolds broke apart 3 60% Vol. Y7 2 2 5 n Scaffolds broke apart 70% Vol. Y7 2 not permeable 70% Vol. NaCl 1.92E -05 , 1 not permeable 60% Vol. NaCl 9.19E -06 , 4 not permeable 50% Vol. NaCl Permeability, k (m 2 ) Porosity value
  13. 13. Evaluation with QCT <ul><li>Samples scanned with Scanco μ CT80 </li></ul><ul><li>Porosity evaluated by thresholding by density </li></ul><ul><li>Connectivity of scaffolds evaluated by inspection </li></ul>30.17% 50% Vol. Y7 45.18% 70% Vol. NaCl 23.49% 60% Vol. NaCl Porosity Sample
  14. 14. Error in build processes <ul><li>Print width range 90-115 μ m </li></ul><ul><li>Surface to volume ratio higher than initial calculation due to print error </li></ul>
  15. 15. SEM of Scaffolds <ul><li>Imprint of solubilized face shown </li></ul><ul><li>Build imperfections negligible </li></ul>
  16. 16. Results <ul><li>Higher surface/volume ratio contributes to increase in permeability </li></ul><ul><li>Interconnectedness prevents fabrication of scaffolds in acrylic at high porosity </li></ul><ul><ul><li>Lower porosity gives higher permeability as compared to NaCl scaffolds </li></ul></ul>
  17. 17. Results <ul><li>Global shape can be built using RP processes </li></ul><ul><ul><li>Build error may limit complex architectures </li></ul></ul><ul><li>Rapid prototyping can be used to explore architecture for use as injectable composite </li></ul><ul><ul><li>Future build processes would need to include speed as design demand - photocrosslinking </li></ul></ul>
  18. 18. Future Directions <ul><li>Determine a dependence of architecture on pore size resulting in solid </li></ul><ul><li>FEA of geometry for optimal permeability </li></ul><ul><li>Correlate surface to volume ratio with permeability </li></ul>
  19. 19. Acknowledgements <ul><li>Computational and Experimental Biomechanics Laboratory </li></ul><ul><li>Mikos Research Group </li></ul><ul><li>Funding Source </li></ul><ul><ul><li>Texas ATP Grant </li></ul></ul>
  20. 20. Thank You

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