Modification Of Apparent Scaffold Properties Through Porogen Surface To Volume Ratio Manipulation, 4/2004

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Information about Modification Of Apparent Scaffold Properties Through Porogen Surface To...

Published on September 3, 2008

Author: organprinter

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Description

Poster presented at the 50th Meeting of the Orthopaedic Research Society, San Francisco CA

ABSTRACT
MODIFICATION OF APPARENT SCAFFOLD PROPERTIES THROUGH POROGEN SURFACE TO VOLUME RATIO MANIPULATION

*Wettergreen, M A; **Pan, J E; *Lemoine, J J; *Mikos, A G; +*Liebschner, M A K
*Rice University, TX, 77251,

INTRODUCTION
Transfer properties through scaffolds are a determining factor for their success in vivo. The ability of the architecture to be perfused by a liquid plays a large role in the degradation and nutrition delivery to encapsulated cells within. Permeation properties have been shown to be directly related to pore size and (with a lower correlation) to pore volume and surface area. The architecture and arrangement of the pore structures (void volume) also plays a large role in the determination of mechanical properties of the composite solid. Optimal scaffold design includes the introduction of porous structures into which cells and fluid can travel while maintaining a mechanically stable structure.
Current predictive models of permeability with high correlation rely upon several “pore structure” parameters. The goal of these parameters is to quantitatively describe the microenvironment of the pores that inhibit or promote fluid flow [1]. While values such as tortuosity and threshold diameter have accounted for some architectural concerns, the effects due to surface chemistry have yet to be explored. New models incorporating surface charge and hydrophobic interactions would help to further describe the microenvironment responsible for fluid flow.
The hypothesis of this study was that by using a porogen with an increased surface/volume ratio, the resulting hydraulic permeability will be higher than when using a standard sodium chloride porogen. There were two goals of this study: 1) Construct porous scaffolds using porogens with varying architecture and surface/volume ratio and 2) Measure and compare pore structure parameters to current mathematical models.

METHODS
Porogens with varying architectures (Figure 1) were generated using CAD processes and then built using rapid prototyping (Patternmaster, SolidScape, Merrimac, NH) and molding techniques. Scaffolds of varying porosities (60, 70, and 80%) were generated by incorporating either the prototyped or salt porogens into poly(propylene fumarate) (PPF). Following crosslinking of the PPF, leaching of scaffolds with salt porogens was performed in H2O; scaffolds with prototyped porogens were first placed in DMSO and then H2O. Scaffolds were then scanned using a μCT 80 (Scanco Medical, Basserdorf, Switzerland) to evaluate porosity and permeability. Slice images from μCT were used to evaluate average pore size of scaffolds. Following scanning, scaffolds were placed in a steady-flow permeability apparatus to determine hydraulic permeability. Finally,. mercury intrusion porosimetry (MIP) was completed on scaffolds to evaluate porosity and pore size distribution.

RESULTS
The use of porogens with high surface to volume ratio results in an increase in permeability of the resulting scaffold as long as 1) The pore size of the resulting solid is kept above a critical value promoting hydraulic flow and 2) pore volume is high enough to ensure that the pores are interconnected. Mechanical compression data demonstrated a relation between porosity and mechanical integrity. Comparison of the two models of permeability demonstrated that the arrangement of pore volumes has a direct effect upon the mechanical strength of the solid structure [2].

DISCUSSION
This study investigated methods to improve the transport properties of porous scaffolds by modifying the surface to volume ratio of the porogens used. By increasing the surface/volume ratio of the porogens, while maintaining pore size above critical threshold values, permeability of a polymer scaffold can be increased over values obtained with normal porogens. Consistent wi

all measured INTRODUCTION The ease with which fluid may flow through a porous solid, or permeability, is one of the most important transfer parameters in tissue engineering because of its direct relation to flow rate and thus shear stress. While an adequate permeability is desired for cell seeded scaffolds, only porosity, a volumetric measure of void space, can be created. The optimal environment of a scaffold is currently unknown, but by modulating the architecture of the void volume, a more permeable scaffold may be obtained. Modeling of this void volume may aid in the design of scaffolds that are optimized for a specific fluid profile. CONCLUSIONS An increase in permeability as a result of surface/volume ratio of the porogens was demonstrated; permeabilities were within the range of trabecular bone (3.0E-6 – 2.0E-4) Results agree with previous research (Scheidegger) indicating increase in permeability as function of surface area modulation Error matches previous studies (Breysse); similar specimens may exhibit orders of magnitude difference in results Surface/volume ratio at fixed porosity reaches a maxima above which the volume of the polymer is not sufficient to coat all of the porogen while still maintaining mechanical integrity Current theoretical models do not take into account complex geometry, may need to use reverse engineering to develop predictive model through curve fitting Hierarchical model or network model combined with topological concepts may be optimal for the complete representation and determination of the fluid properties ACKNOWLEDGEMENTS The SEM images where prepared by Adam Horch REFERENCES 1) Dullien, FAL. Porous Media: Fluid Transport and Pore Structure. 1979, Academic Press, New York. 2) Scheidegger, AE, The Physics of Flow Through Porous Media. 1974, University of Toronto Press, Toronto. 3) Arramon YP, Nauman EA. The Intrinsic Permeability of Cancellous Bone. Cowin SC, editor. Bone Biomechanics Handbook. Boca Raton: CRC Press LLC; 2001:(25)1-(25)41. 4) Breysse D, Gerard B. Modeling of Permeability in Cement-based materials: part 1–uncracked medium. Cem Concr Res, 1997. 27(5): p. 761-775. MODIFICATION OF APPARENT SCAFFOLD PROPERTIES THROUGH POROGEN SURFACE TO VOLUME RATIO MANIPULATION *Wettergreen, M A; **Pan, J E; *Lemoine, J J; *Mikos, A G; *Liebschner, M A K *Department of Bioengineering, Rice University, Houston, TX **Harvard University, Boston, MA PHENOMENOLOGICAL MODEL Permeation factor, K (m/s), is exponentially related to parameters. Includes empirically calculated parameters. PERMEABILITY EVALUATION Hypothesis – Modulation of surface to volume (S/V) ratio of void space will result in an altered permeability. CAD architectures for use as porogens in solvent leaching process to create porous solids. Axial hydraulic permeability, k (m 2 ), as measured from a constant flow permeameter. Asterisk porogen permeability was 25 times greater than NaCl scaffold Y-Shape permeability was 6.5 times NaCl permeability A Large error exists between samples due to the random network Asterisk and Y7 Scaffolds at 76% porosity had no mechanical integrity and crumbled Phenomenological model overestimated permeability Remaining models grossly underestimated porosity Hydraulic radius only model that takes into account surface area HYDRAULIC RADIUS MODEL Extension of capillary models to include effect due to surface area and volume of pores CAPILLARY MODELS Right: Serial capillary model with uniform length, pore length s, and pore average pore diameter δ Left: Y-shape approximation of model Right: Straight capillary model with uniform length and diameter Left: Y-Shape approximation of model MATHEMATICAL MODELING Numerous models exist to predict transfer properties, however, none are able to correctly correlate permeability with porosity for random architectures. The pores created by the Y- shape are a combination of a capillary with a complex pore while the asterisk may at worst be viewed as a capillary with 6 dead pores. Comparison of actual results with standard models of transfer properties was conducted. DETERMINATION OF PORE ARCHITECTURAL PARAMETERS RESULTS COMPARISON OF MODELS TO EXP. RESULTS 1.58E-02 7.64E-03 Phenomenological 1.11E-06 1.04E-06 Drag Theory 7.05E-08 3.88E-08 Hydraulic Radius 1.10E-08 9.47E-09 Serial Capillary 1.21E-08 1.04E-08 Straight Capillary 5.47E-04 1.71E-04 Measured Permeability 64% Y-Shape 55% Y-Shape Cross-Sectional Area (m 2 ) Scaffold Length (m) Pressure Drop (N/m 2 ) Flow Rate (m 3 /s) Darcy’s Law of Permeability Where: DRAG MODEL Opposite of Capillary model. Capillaries are obstructions to flow. δ s x s x δ Determination of pore micro-architectural parameters using SEM and µ CT evaluation. Pore micro-architectural parameters measured from SEM and µ CT. Porogen Dimensions Measured from Imaging 0 200 400 600 800 1000 Arm Length Leg Width Leg Length Dimension (um) Designed SEM uCT Main flow channel Trapped pore contributes to porosity but not permeability Dead-end pore contributes to porosity and permeability

CONCLUSIONS

An increase in permeability as a result of surface/volume ratio of the porogens was demonstrated; permeabilities were within the range of trabecular bone (3.0E-6 – 2.0E-4)

Results agree with previous research (Scheidegger) indicating increase in permeability as function of surface area modulation

Error matches previous studies (Breysse); similar specimens may exhibit orders of magnitude difference in results

Surface/volume ratio at fixed porosity reaches a maxima above which the volume of the polymer is not sufficient to coat all of the porogen while still maintaining mechanical integrity

Current theoretical models do not take into account complex geometry, may need to use reverse engineering to develop predictive model through curve fitting

Hierarchical model or network model combined with topological concepts may be optimal for the complete representation and determination of the fluid properties

Asterisk porogen permeability was 25 times greater than NaCl scaffold

Y-Shape permeability was 6.5 times NaCl permeability

A Large error exists between samples due to the random network

Asterisk and Y7 Scaffolds at 76% porosity had no mechanical integrity and crumbled

Phenomenological model overestimated permeability

Remaining models grossly underestimated porosity

Hydraulic radius only model that takes into account surface area

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