Design of a Three-Dimensional Composite Scaffold with Varied Engineered Micro-Architecture, 3/14/2003


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Design of a Three-Dimensional Composite Scaffold with Varied Engineered Micro-Architecture

Wettergreen, MA, Mikos AG, Liebschner, MAK

Department of Bioengineering, Rice University, Houston, TX.

The ultimate goal for tissue engineers is the design and complete control of a three-dimensional scaffold for use in implantation. Through the use of microfluidics, soft lithography, and other patterning methods, the two-dimensional environment can be modified and engineered to specifications based upon the intended use for the scaffold. While the two-dimensional surfaces modified in laboratory experiments are far from mimicking the existing environment of the body, it is hoped that the use of these techniques will soon provide a breakthrough allowing researchers to expand upon current techniques and generate a three-dimensional model of tissue. Current rapid prototyping methods for the generation of three-dimensional scaffolds utilize molds designed for only one material, creating scaffolds which are isotopic throughout. Joints in the human body, however, are composed of several distinct regions with varied material properties. As such, scaffold generation methods should incorporate multiple materials with different mechanical properties, creating constructs which better imitate the native tissue.

The goal of this study is to develop a novel process for the fabrication of an engineered scaffold with distinct regions, each consisting of different materials for the creation of a scaffold mimicking the Temporomandibular joint (TMJ) disc (see Fig 1). The TMJ disc is a donut shaped structure containing three distinct regions, each with differing mechanical properties (see Table 1). Using a combination of rapid prototyping and molding techniques, a three-dimensional scaffold with varied architecture is built utilizing multiple materials possessing drastically different material properties. Using computer aided design and Finite Element Modeling, the architecture (based on regular polyhedra) of each region will be tailored to the mechanical property requirements of the region. The resulting construct has diverse mechanical characteristics that mimic the mechanical strength of the TMJ disc.

The results of this study represent the first step in the complete control over the three-dimensional environment of a scaffold. The distinct architectures created in the scaffold will offer variability in mechanical strength and porosity. The different materials used in the fabrication vary in their cell attachment and degradation times. Using this same technique, design of other three-dimensional scaffolds can be accomplished.

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Design of a Three-Dimensional Composite Scaffold with Varied Engineered Micro-Architecture, 3/14/2003

  1. 1. Design of a Three-Dimensional Composite Scaffold with Varied Engineered Micro-Architecture Matthew A Wettergreen, Mark D Timmer, Antonios G Mikos, Michael AK Liebschner 13 th GRIBOI March 14 th , 2003 Rice University Computational and Experimental Biomechanics Laboratory
  2. 2. Background <ul><li>Cellular environment infinitely complex </li></ul><ul><ul><li>Intricate consistently remodeled architecture </li></ul></ul><ul><ul><li>Complicated nutrient requirements </li></ul></ul><ul><ul><li>Mass of mechanical signals </li></ul></ul><ul><li>Complex environment leads to tissue function </li></ul><ul><li>In vitro techniques attempt to approximate 3-D environment </li></ul><ul><ul><li>Fails to address many characteristics </li></ul></ul>
  3. 3. Importance of 3-D environment <ul><li>Gene Regulation </li></ul><ul><ul><li>Shear flow modulates MMPs of endothelial cells </li></ul></ul><ul><li>Differentiation </li></ul><ul><ul><li>Concentration gradient in embryogenesis </li></ul></ul><ul><li>Mechanical forces influence function </li></ul><ul><ul><li>Shear flow modulates bone deposition </li></ul></ul><ul><li>Cell attachment and spreading </li></ul><ul><ul><li>ECM provides matrix for fibroblasts in wound healing </li></ul></ul>
  4. 4. History of Cell Culture <ul><li>Chick embryo maintained in fluid, 1880 </li></ul><ul><li>Aseptic Technique introduced, 1923, Carrel </li></ul><ul><ul><li>Demonstrated that cells were immortal in culture </li></ul></ul><ul><li>Media defined, 1950’s </li></ul><ul><li>3-D studies with gels proposed, 1972 </li></ul><ul><li>Scaffolds with 3-D geometry, 1990’s </li></ul><ul><li>Biomimetic scaffolds with true 3-D characteristics, ??? </li></ul>
  5. 5. Current State of Affairs <ul><li>3-D scaffolds – extrusion of 2-D shape? </li></ul><ul><ul><li>Lacks complex architecture </li></ul></ul><ul><li>Current fabrication methods </li></ul><ul><ul><li>Salt leaching </li></ul></ul><ul><ul><li>Gas elution </li></ul></ul><ul><li>Differences in regions of scaffold due to random action of porogen </li></ul><ul><li>One trick pony </li></ul>May not result in permeability
  6. 6. Requirements <ul><li>Porosity similar to tissue </li></ul><ul><li>Strength matching </li></ul><ul><li>Sites for specific cell adhesion </li></ul><ul><li>Surface topology </li></ul><ul><li>Biomaterial tailored to region </li></ul>
  7. 7. Goal <ul><li>Porosity similar to tissue </li></ul><ul><li>Strength matching </li></ul><ul><li>Sites for specific cell adhesion </li></ul><ul><li>Surface topology </li></ul><ul><li>Biomaterial sufficient for desired region </li></ul><ul><li>Build mold with varying architectures reflecting differences in tissue area </li></ul>
  8. 8. Region of Study <ul><li>Temporal Mandibular Joint Disc </li></ul><ul><li>Located on Mandibular condyle matching with the cranium </li></ul><ul><li>Provide shock absorption for jaw movement </li></ul><ul><li>TMJ Disorder may be due to dysfunction of disc </li></ul><ul><li>Why analyze for this project (can be sectioned into 3 pieces) </li></ul>
  9. 9. Methodology <ul><li>Remove TMJ Disc </li></ul><ul><li>Scan </li></ul><ul><li>Make CAD file </li></ul><ul><li>Create architecture </li></ul><ul><li>Build scaffold </li></ul><ul><li>Inject scaffold with </li></ul><ul><li>biomaterial </li></ul><ul><li>Dissolve mold </li></ul>
  10. 10. Excision of TMJ Disc
  11. 11. Creation of TMJ Disc Positive CAD file of scanned disc Rapid Prototyped disc Excised Porcine disc μ CT slice of disc
  12. 12. Disc Generation <ul><li>Embedding of prototyped disc in Silicon </li></ul><ul><ul><li>Mold created </li></ul></ul><ul><li>Inject mold to obtain exact replica of TMJ Disc </li></ul>
  13. 13. Scaffold with Composite Materials <ul><li>Inject mold with biomaterials </li></ul><ul><li>Clear mold allows usage of photocrosslinking </li></ul><ul><li>Material Choice </li></ul><ul><ul><li>1,3 Butanediene </li></ul></ul><ul><ul><li>Poly (propylene fumarate) Diacrylate </li></ul></ul><ul><ul><li>Poly (Ethylene Glycol) Diacrylate </li></ul></ul>
  14. 14. Scaffold Generation Completed Scaffold with 1,3 Butane… & PPF-DA Blue light for crosslinking Inject material Crosslink material Inject 2 nd material
  15. 15. Scaffold Generation 2 <ul><li>Completed scaffold with </li></ul><ul><li>PPF-DA/PEG-DA </li></ul><ul><li>PEG-DA swells like Hydrogel </li></ul><ul><ul><li>Confined on sides due to PPF </li></ul></ul>
  16. 16. Complex Architecture Scaffold ( μ CT + FEA + CAD Method ) <ul><li>TMJ Disc is orthotropic </li></ul><ul><li>Generate composite scaffold with differing architecture </li></ul><ul><ul><li>Begin with CAD file of disc following scanning and reconstruction </li></ul></ul><ul><ul><li>Add engineered architecture that reflects mech. prop. </li></ul></ul>23.40 ± 6.5 Posterior Band .58 ± .39 Intermediate Zone 9.48 ± 3.32 Anterior Band Modulus (MPa) Location
  17. 17. Creation Process (CAD Directions) <ul><li>Tedious, lengthy procedure </li></ul><ul><li>Positive / Negative processing of shape </li></ul><ul><li>Begin with global shape (scanned TMJ Disc) </li></ul><ul><li>End with global shape with engineered micro-architecture </li></ul>
  18. 18. /3
  19. 23. Scaffold Creation <ul><li>Build mold </li></ul><ul><li>of scaffold </li></ul><ul><li>with RP </li></ul>One use mold due to interconnected pores
  20. 24. Conclusions <ul><li>Combining μ CT and Rapid Prototyping methods, composite scaffolds can be created which contain intricate architecture </li></ul><ul><li>Architecture may modulate apparent strength of scaffold as well as strength of location </li></ul><ul><li>Process detailed may be used to design architecture for any tissue </li></ul><ul><li>Results show first step towards creating fully engineered scaffold which mimics the three-dimensional environment </li></ul>
  21. 25. Acknowledgements <ul><li>Musculoskeletal Laboratory </li></ul><ul><ul><li>Alex Almarza, Michael Detamore </li></ul></ul><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>
  22. 26. Thank you