rp techniques for tissue engineering purposes author: evgeny barabanov
TRANSCRIPT
RP techniques for tissue
engineering purposesAuthor: Evgeny Barabanov
Scaffold in tissue engineering
Scaffold in tissue engineering is an artificial structure capable of supporting three-dimensional tissue formation.
Cells are often implanted or 'seeded' into a scaffold
Scaffold purposes
Requirements
To achieve the goal of tissue reconstruction, scaffolds must meet some specific requirements
Requirements
A high porosity and an adequate pore size
Requirements
A high porosity and an adequate pore size
To facilitate cell seeding and diffusion throughout the whole structure of both cells and nutrients.
Requirements
A high porosity and an adequate pore size
To facilitate cell seeding and diffusion throughout the whole structure of both cells and nutrients
Biodegradability
Requirements
A high porosity and an adequate pore size
To facilitate cell seeding and diffusion throughout the whole structure of both cells and nutrients
Biodegradability
To allow absorption by the surrounding tissues without the necessity of a surgical removal
Requirements
A high porosity and an adequate pore size
Necessary to facilitate cell seeding and diffusion throughout the whole structure of both cells and nutrients
Biodegradability
To allow absorption by the surrounding tissues without the necessity of a surgical removal
Customizability
Requirements
A high porosity and an adequate pore size
To facilitate cell seeding and diffusion throughout the whole structure of both cells and nutrients
Biodegradability
To allow absorption by the surrounding tissues without the necessity of a surgical removal
Customizability
To allow fabrication into various shapes and sizesfor matching the each patient’s individual needs
Limitations of conventional methods
Lack of precise control of scaffold properties
Exploitation of organic solvents as a part of the synthetic polymers dissolution process (toxic and cancerogenic).
Limitations of conventional methods – example
Inhomogeneities of pore distribution
Irregular pore size distribution
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Rapid prototyping of bone and cartilage
Rapid prototyping of bone and cartilageIdeally, bone grafts should be porous, be able to promote new bone formation, and they should possess proper mechanical and physical properties.
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Rapid prototyping of bone and cartilage
First used in cranio-maxillofacial surgery
Pioneered by Griffith and coworkers at MIT
In 1996 Griffith and Halloran reported the fabrication of ceramic parts by stereolithography
Stereolithography (SLA)Hydroxyapatite (HA) scaffolds fabrication for orbital floor implants (by Levy et al.)
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Stereolithography (SLA)Minimum pore size of 100 μm is required for mineralized tissue ingrowth.
CAD modelof the scaffold
SLA fabricatedscaffold
Micro-CT imageof the scaffold
The Micro-CT scan reveals that the scaffold has a veryregular pore size distribution in the range of 315-659 μm
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Stereolithography (SLA)
Disadvantages:
Stereolithography (SLA)
Disadvantages: Requires the use of supporting structures
Stereolithography (SLA)
Disadvantages: Requires the use of supporting structures
• To attach the part to the elevator platform
• To prevent deflection due to gravity
• To hold the cross sections in place so that they resist lateral pressure from the re-coater blade.
Stereolithography (SLA)
Disadvantages: Requires the use of supporting structures
• To attach the part to the elevator platform
• To prevent deflection due to gravity
• To hold the cross sections in place so that they resist lateral pressure from the re-coater blade.
Although supports are generated automatically during the preparation of CAD models, they must be removed from the finished product manually.
Stereolithography (SLA)
Disadvantages: Requires the use of supporting structures
Limited materials (photo polymers)
Stereolithography (SLA)
Disadvantages: Requires the use of supporting structures
Limited materials (photo polymers)
Extremely expensive
Stereolithography (SLA)
Disadvantages: Requires the use of supporting structures
Limited materials (photo polymers)
Extremely expensive
Advantages:
Stereolithography (SLA)
Disadvantages: Requires the use of supporting structures
Limited materials (photo polymers)
Extremely expensive
Advantages: Relatively fast (functional parts can be
manufactured within a day)
Three-dimensional printing (3DP)
Was developed at the Massachusetts Institute of Technology (MIT)
Uses a liquid adhesive that binds the material
Uses a powder as a material
Three-dimensional printing (3DP)
Advantages: Does not require supporting structures
Three-dimensional printing (3DP)
Advantages: Does not require supporting structures
The remaining free standing powder supports the part during the build
Three-dimensional printing (3DP)
Advantages: Does not require supporting structures
The remaining free standing powder supports the part during the build
Inexpensive
Three-dimensional printing (3DP)
Advantages: Does not require supporting structures
The remaining free standing powder supports the part during the build
Inexpensive
Disadvantages:
Three-dimensional printing (3DP)
Advantages: Does not require supporting structures
The remaining free standing powder supports the part during the build
Inexpensive
Disadvantages: Accuracy, surface finish, and part strength
are not quite as good as some other additive processes
Selective laser sintering (SLS) Was developed and patented by Dr. Carl Deckard
and academic adviser, Dr. Joe Beaman at the University of Texas in Austin in the mid-1980s
A combination of SLA and 3DP
Selective laser sintering (SLS)
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Selective laser sintering (SLS)SLS provides a cost-effective, efficient method to construct scaffolds to match the complex anatomical geometry of craniofacial or periodontal structures
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Selective laser sintering (SLS)Advantages: A wide range of materials can be used
(including metals)In fact any powdered biomaterial that will fuse but not decompose under a laser beam can be used to fabricate scaffold by SLS.
Accurate (very complex geometries can be created directly from digital CAD data)
Fabricated prototypes are porous
Does not require the use of any organic solvent
Fused deposition modeling (FDM)
Was developed by S. Scott Crump in the late 1980s and was commercialized in 1990 by Stratasys in Eden Prairie, Minnesota
Uses semiliquid-state thermoplastic polymer as a material
Two heads with a fixed distance in between
Fused deposition modeling (FDM)
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Fused deposition modeling (FDM)
Can be used as a bone patch to repair holes in the skull
PCL(Polycaprolactone)scaffold
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Fused deposition modeling (FDM)
Advantages: Easy material changeover
Disadvantages: Support design / integration / removal is difficult
Soft tissue scaffolds by the means of RP
Soft tissue scaffolds by the means of RP
The requirements of soft tissue implants differ from hard tissue replacements
Soft tissue has a very high content of water, so from the chemical point of view it is a hydrogel.
Hydrogels
Polymers
Can absorb water even 10 times specimen’s original weight without disintegrating (only swelling)
Can be used as simple scaffold structures, like sheets, fibers, wovens or non-wovens
Proven to be excellent candidates for substituting soft tissues
Hydrogel scaffolds
Advantages:
Hydrogel scaffolds
Advantages: Flexible
Hydrogel scaffolds
Advantages: Flexible
Similar to the extracellular matrix
Hydrogel scaffolds
Advantages: Flexible
Similar to the extracellular matrix
Permeability to oxygen and metabolites
Hydrogel scaffolds
Advantages: Flexible
Similar to the extracellular matrix
Permeability to oxygen and metabolites
Disadvantages:
Hydrogel scaffolds
Advantages: Flexible
Similar to the extracellular matrix
Permeability to oxygen and metabolites
Disadvantages: Mechanical stability of hydrogels does not allow
the use in stress-loaded implants
Hydrogel scaffolds
Advantages: Flexible
Similar to the extracellular matrix
Permeability to oxygen and metabolites
Disadvantages: Mechanical stability of hydrogels does not allow
the use in stress-loaded implants
Cannot be produced with SLA, SLS, 3DP and FDM due to their processing conditions
3D Bioplotter
Developed at the Freiburg Materials Research Center
Can produce hydrogel scaffolds
3D Bioplotter
Advantages: Allows to integrate living cells into scaffold
fabrication process
No support structure is needed(the liquid medium compensates for gravity)
Two-photon polymerization Uses two-photon absorption and subsequent
polymerization
Allows fabrication of any computer generated 3D structure by direct laser “recording” into the volume of a photosensitive material
Allows real-time monitoring of the polymerization process
Two-photon polymerization
Overlap of photons from the ultra short laser pulse leads to chemical reactions between monomers and starter molecules within transparent matrix.
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Two-photon polymerizationAdvantages: Provides much better resolution than other RP
methods
Can handle very complex structures
Potential advantages and challenges of rapid prototyping processes in tissue engineering
Advantages
Advantages
Production of three-dimensional scaffolds with complex geometries and very fine structures
Advantages
Production of three-dimensional scaffolds with complex geometries and very fine structures
High customizability
Advantages
Production of three-dimensional scaffolds with complex geometries and very fine structures
High customizability
Control of the scaffold porosity
Advantages
Production of three-dimensional scaffolds with complex geometries and very fine structures
High customizability
Control of the scaffold porosity
Speed - three-dimensional parts can be manufactured in hours and days instead of weeks and months
Advantages
Production of three-dimensional scaffolds with complex geometries and very fine structures
High customizability
Control of the scaffold porosity
Speed - three-dimensional parts can be manufactured in hours and days instead of weeks and months
Several RP techniques operate without the use of toxic organic solvents
Challenges
Challenges
Surface roughness
Challenges
Surface roughness
Resolution
Challenges
Surface roughness
Resolution
Internally trapped materials
Challenges
Surface roughness
Resolution
Internally trapped materials
Environment requirements
Challenges
Surface roughness
Resolution
Internally trapped materials
Environment requirements
Temperature
Challenges
Surface roughness
Resolution
Internally trapped materials
Environment requirements
Temperature
Sterility
Summary
Although RP methods already can serve as a link between tissue and engineering, every RP process has its own unique disadvantages in building tissue engineering scaffolds.
Hence, the future research should be focused into the development of RP machines designed specifically for fabrication of tissue engineering scaffolds.
References
A review of rapid prototyping techniques for tissue engineering purposes
Two-photon polymerization: A new approach to micromachining
Additive fabrication
Rapid prototyping
Tissue engineering