RP techniques for
tissue engineering
purposes
Author: Evgeny Barabanov
Tissue engineering
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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
Example - carbon nanotube
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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 sizes
for 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
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Irregular pore size
distribution
Rapid prototyping of bone
and cartilage
Rapid prototyping of bone
and cartilage
Ideally, 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)
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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 model
of the scaffold
SLA fabricated
scaffold
Micro-CT image
of the scaffold
The Micro-CT scan reveals that the scaffold has a very
regular 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)
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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)
PCL
(Polycaprolactone)
scaffold
Can be used as a bone patch to repair holes in the skull
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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
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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 polymerization
Advantages:

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