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Characterization of porous scaffold materials for bone tissue
engineering - Saartje Impens -
Micro-CT symposium 31/05/07
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
Bone defect
Operation Room
Patient own cells + growth
factors
Scaffold
Haeled bone defect
Bioreactor
Scaffold seeding and culturing with cells
In vitro
Cells + medium
Macrostructural & Mechanical parameters
Fluid Flow
input = cells
3D cell seeding
time point analysis
2D plates
3D cell culture
Optimization possible?
If 2D plates are possible
2D cell seeding
2D cell culture
µ-CT screening
3D scaffold
output = proliferation
differentiation
in vivo screening nude mice
Not Ok
Ok
Not Ok
Ok
input = material + coating +
growth factors
Toxicity testing
NoREJECT
Optimize scaffold
Yes
Further screening until clinical approvement
Macrostructural shortcoming
No perfusion perfusion possible
No
Yes
Clinical approved scaffold
Yes
Yes
No
No
2. High throughput screening
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
Scaffold: Ø 6 mm, L 8 mm
Inflow: 1 ml/min
Figures: Tim van Cleynenbreugel
• 3D Fluid flow on CAD-based model
1. Scaffold characterization
Figures: Silvia Truscello
1. Scaffold characterization
• Problems occur when meshing regular scaffolds produced by rapid prototyping
Blue Best
VioletPinkOrangeRed 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
Histologicalimage
Binarized histologicalSection
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?
Difficult, depends on scaffold material
Bone
Scaffold
Zone of bone ingrowth
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
AcknowledgementSpecial thanks goes to:
• Jan Schrooten• Tim van Cleynenbreugel• Barbara Neirinck• Silvia Truscello• Greet Kerckhofs
-Thanks-
-Thanks-