07 05 31 micro CT sympsosium Saartje by flwifnVD

VIEWS: 12 PAGES: 22

									Micro-CT symposium 31/05/07




Characterization of porous scaffold
    materials for bone tissue
           engineering
                         - Saartje Impens -
                 GBE project
•    2 different aims:

    1. Setting up a protocol for the healing of large
       and complex, but critical bone defects

    2. High throughput screening of different
       scaffolds (= porous structure)

        With the aid of micro-CT evaluation
  1. Healing of critical bone defects
           Scaffold       Scaffold seeding and
                           culturing with cells




                                      Cells +
                                      medium



                        Bioreactor
Bone Patient own                                  Operation Haeled
defect cells + growth
           factors                                 Room      bone
                                                            defect
                               In vitro
                                  input = material
2. High                             + coating +
                                                                     Optimize
                                                                     scaffold
                                   growth factors
throughput                        Toxicity testing
screening                                                                                         Yes
                                                                                                                Clinical
                                               Not Ok                                   No                     approved
                                                               REJECT                                           scaffold

                   If 2D plates are   Ok
                       possible
                                                                                        Optimization
  2D plates                                 3D scaffold                                  possible?                  Yes
                                                                                                          No
                      Macrostructural & µ-CT screening              Macrostructural
                     Mechanical parameters                           shortcoming
                         Fluid Flow                                                                     Further screening until
                                                          Not Ok                                         clinical approvement

                   input = cells                                                                                     Yes
                                              Ok                                                          No
                                                                     No perfusion
                                                                   perfusion possible
2D cell seeding                            3D cell seeding
                                                                                                          in vivo screening
                                                                                                              nude mice
2D cell culture                            3D cell culture
                                                                                             No
                                                                        output =                        Yes
                  time point analysis                                 proliferation
                                                                     differentiation
             GBE strategy
• Multidisciplinary approach
               Micro-CT use
1. Micro-CT based characterization of scaffolds
  –   Calculate structural parameters
  –   Calculate mechanical parameters with the aid of a
      FE-model
  –   Calculate fluid flow


2. Evaluation of bone formation in explanted
   scaffold
  –   Replacement of histology?
     1. Scaffold characterization
• Important parameters for bone formation in Matlab
   – Porosity                   As high as possible (100%)
   – Specific surface area      As high as possible
       (Mentat)                 >3,95mm-1 (Ding et al. based on bone)
   – Pore size                  100-800µm
       (PorousAnalyser)
   – Permeability               As high as possible
       (PoreNet)                 > 10-8m2 (Kohles et al. based on bone)
   – Interconnectivity          As high as possible (100%)

• Mechanical parameters with FE-modeling (Mesh creation in Matlab)
   Expected load during walking is 1,2 x body weight
   – Strength                   100% under yield strength
   – Stiffness                  17-20 GPa (cortical bone)
                                 10-1500MPa (trabecular bone)
   – Stretch on surface         (500-)1500-4000µstrain
   1. Scaffold characterization




Scaffolds   Reconstructed micro-CT   FE-mesh
                 Image
   1. Scaffold characterization
• Structural and biomechanical parameters
     Scaffold characterization
• Extra important parameter for the GBE project
  – Fluid flow
     • Nutrient & Oxygen transport
  – Wall shear stress
     • May stimulate proliferation and differentiation
       i.e. May stimulate bone formation




Ideally Computing Fluid Flow of micro-
 CT based models
   1. Scaffold characterization
• 2D Fluid flow on µCT based model
                                Inflow: 1 ml/min




                                          Scaffold:
                                          Ø 6 mm, L 8 mm




  Figures: Tim van Cleynenbreugel
       1. Scaffold characterization
• 3D Fluid flow on CAD-based model




Figures: Silvia Truscello
   1. Scaffold characterization
• Problems occur when meshing regular
  scaffolds produced by rapid prototyping

                              Blue  Best
                              Violet
                              Pink
                              Orange
                              Red  Worst
                                    Manually
                                    remeshing
    2. Substitute for Histology
• Evaluation different scaffold materials
  – Time consuming
     • Embedding 2 weeks
     • Sectioning
        – 1 scaffold/day
        – Labor intensive
     • Staining
        – 1 day                     *
     • Analysis
        – 1 scaffold/day
        – Labor intensive
1. Scaffold characterization
    2. Substitute for Histology
• Polymer scaffolds
                           Binarized histological
                           Section
            Histological
            image


                           Interpolated
                           micro-CT image



                           After registration
                            Green: Overlap
                            Blue: only histology
                            Red: only micro-CT
    2. Substitute for Histology
• Distinguish between scaffold and bone by
  thresholding?
                        Bone


                        Scaffold


                        Zone of bone ingrowth


                         Difficult, depends on
                          scaffold material
    2. Substitute for Histology
• Micro-CT analysis
  – Micro-CT Scanning

  – Micro-CT scanning
    explant

  – Positioning and subtrac-
    ting in Mimics to
    determine the amount
    of bone ingrowth
2. Substitute for Histology
                     Conclusion
• Micro-CT is a very useful tool for this type of
  research
   – Scaffold parameters can be calculated
      • Prior to implantation
      • Non destructive
   – Time consuming histology
      • Can be replaced
      • If necessary, histology can be performed after scanning
• If FE models and meshing problems are solved
   – Fluid flow
   – Wall shear stresses
  can be calculated
               Acknowledgement
Special thanks goes to:

•   Jan Schrooten
•   Tim van Cleynenbreugel
•   Barbara Neirinck
•   Silvia Truscello
•   Greet Kerckhofs




                             -Thanks-
-Thanks-

								
To top