Download Computer Aided Design of Scaffolds for Tissue Engineering

INTERNATIONAL JOURNAL OF COMPUTATIONAL INTELLIGENCE AND HEALTHCARE INFORMATICS
Vol. 4, No. 2, July-December 2011, pp. 105-109, Published by Serials Publications, ISSN: 0973-7413
Computer Aided Design of Scaffolds for
Tissue Engineering Applications
K. Pramanik1 and Ipsita Dipamitra Behera2
1
Department of Biotechnology and Medical Engineering, National Institute of Technology, Rourkela, Orissa, India.
E-mail: [email protected]
2
Department of Chemical Engineering, National Institute of Technology, Rourkela, Orissa, India.
E-mail: [email protected]
ABSTRACT: Tissue engineering is a promising technique to replace or repair tissues or organs because of disease, trauma or
congenital problems. However, the design and fabrication of 3-D scaffold is crucial for the success of this technique. In this
context, the use of computer aided techniques seems to be attractive for the design and fabrication of tissue scaffolds systematically.
In this paper the various computational approaches like Computer Aided Tissue Engineering (CATE), Solid Freeform Fabrication
(SSF), Image Based Bio-CAD Modeling and Organ Printing have been described for the design and modeling of the tissue
engineering scaffolds.
Keywords: Tissue Engineering, Computer-aided Tissue Engineering, Solid Freeform Fabrication, Bio-CAD, Organ
printing, Scaffold
1. INTRODUCTION
The loss or failure of an organ or tissue is one of the most
frequent, traumatic and expensive ailments in human health
care. Millions of people every year suffer from various organ
and tissue-related maladies including burns, skin ulcers,
diabetes, bone, cartilage and connective tissue defects and
diseases worldwide. Though clinicians have tried to replace
the function of failing organs mechanically or through
implantation, these are often only temporary solutions and
do not allow the patient to completely resume normal
activities. Infection and device rejections are the other
serious problems. The need for substitutes to replace or
repair tissues or organs because of disease, trauma, or
congenital problems is overwhelming. Recent research
efforts have focused on tissue engineering as a promising
approach to solve these problems. However, the key
challenges in tissue engineering are the synthesis of new
cell adhesion-specific materials and development of
fabrication methods to produce three dimensional (3D)
synthetic or natural biodegradable polymer scaffolds with
tailor properties having intricate architecture, porosity, pore
size and shape, and interconnectivity in order to provide
the needed structural integrity, strength, transport, and ideal
micro-environment for cell and tissue in growth [1-3]. These
three dimensional (3D) scaffolds play important roles as
extracellular matrices onto which cells can attach, grow and
form new tissues. So, modeling, design and fabrication of
tissue scaffolds to meet multiple biological and biophysical
requirements is of paramount importance in tissue
engineering. Though several scaffold fabrication techniques
have emerged for the production of porous polymer
constructs as substrates for cell attachment, complex
architectures with tunable micro- and macro-scale features
are difficult to achieve. Moreover the traditional scaffold
fabrication techniques use “cell unfriendly” chemicals, UV
or gamma rays, lasers, and high temperatures. It is difficult
to remove traces of precursors and chemicals used in
fabrication, which are often cytotoxic [4]. To overcome the
limitations of the traditional methods, in recent years, CADbased manufacturing technologies are being developed for
the fabrication of tissues. These three-dimensional
fabrication approaches offer several potential opportunities
in tissue engineering. First, the independent control of microand macro-scale features may enable the fabrication of
multicultural structures that are required for complex tissue
function. Second, fabrication of three-dimensional vascular
beds would allow support of larger tissue constructs than
could be otherwise achieved. Third, the combination of
clinical imaging data with three-dimensional fabrication
techniques may offer the capability to create tissue
engineered constructs that are customized to the shape of
the defect or injury. Fourth, such fabrication technology may
allow mass production of many identical tissues constructs
for use in drug discovery or fundamental studies. Further,
the advantage of the CAD with Computer assisted
manufacturing (CAM) is of particular interest to tissue
engineers to reproduce complex scaffold architectures
without requiring the use of moulds, while the engineering
potential of various scaffold architectures is considerable,
the ability to design and optimize structures is still very much
adhoc science local structure and mechanical/transport
properties have not been measurable during tissue growth
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International Journal of Computational Intelligence and Healthcare Informatics
in vitro or in vivo. Hence computer aided design allows to
design different scaffold systematically. So in this paper the
various computational approaches which can be effectively
used to design and modeling of the tissue engineering
scaffolds have been described.
2. COMPUTER AIDED TISSUE ENGINEERING
The application of computer aided technologies in tissue
engineering is known as Computer Aided Tissue
Engineering (CATE). Application of CATE to the design
and fabrication of tissue scaffolds can facilitate the
exploration of many novel ideas of incorporating biomimetic
and biological features into the scaffold design. The various
approaches of Computer aided tissue Engineering are1.
Computer-Aided-Tissue-Scaffold-Design and Manufacturing, including scaffold modeling and design, solid
freeform fabrication of tissue scaffolds, bio-blueprint
modeling for 3D cell and organ printing
2.
Computer-Aided-Tissue-Informatics, including
computer-aided tissue classification and application for
tissue identification and characterization at different
tissue hierarchical levels
3.
Computer-Aided-Tissue-Modeling, including 3D
anatomic visualization, 3D reconstruction and CADbased tissue modeling
3. SOLID FREEFORM FABRICATION
(SFF) TECHNIQUE
SFF refers to CAD/CAM methodologies, which can easily
fabricate arbitrarily complex shapes directly from CAD
models. This model would include not only geometric
information, but it would also specify the temporal and
spatial distributions of the materials, cells, and signaling
molecules throughout the scaffold. The application of solid
freeform fabrication (SFF) to tissue engineering may be the
key to produce scaffolds with customized external shape
and predefined and reproducible internal morphology, which
not only can control pore size, porosity and pore distribution,
but can also make structures to increase the mass transport
of oxygen and nutrients throughout the scaffold. SFF
technologies involve building 3D objects using layered
manufacturing strategies. This technique generates a
computer-generated model using computer-aided design
(CAD) software. This CAD model is then expressed as a
series of cross-sectional layers. The data is then implemented
to the SFF machine, which produces the physical model.
Each layer corresponds to a cross sectional division.
Post-processing may be required to remove temporary
support structures.
However, many SFF techniques are not biologically
friendly using techniques that cannot handle a wide range
of wet materials, gels or solutions, some techniques utilize
harsh solvents, high temperatures, high pressures, and other
factors that are not conducive to biological systems. Many
SFF techniques are though capable of creating tissue
scaffolds, but cannot directly deposit cells or biological
factors into the scaffold such as stereolithography, fused
deposition methods, and powder/binder-based techniques,.
All these factors have led to the development of different
techniques of SSF. As for example, in one newly developed
SFF method scaffolds are incrementally built up from
relatively thin, prefabricated cross-sectional layers of
scaffolding (5 to 1 mm thick). These layers are stacked up
to form 3-D structures by arranging layers together with
miniature biodegradable fasteners. With this assembly
approach, each prefabricated section are first be seeded with
cells and/or growth factors before final assembly. Then
normal tissue growth across the layers, in vivo, fuses the
assembly together as the scaffold degrades. Several types
of tissue connectors are being investigated including
miniature barbs, staples, screws and nuts, as well as
conventional sutures. A method was also developed by Weiss
et al [5] for building bone tissue scaffolds using SFF. This
process consists of taking a CAD model of a
three-dimensional structure of a bone implant, slicing the
model into layers, taking laminated sheets of scaffold
material, seeding the layers with cells or growth factors,
and stacking them on top of each other.
4. IMAGE BASED BIO-CAD MODELING TECHNIQUE
Bio-CAD modeling plays an important role in the scaffold
informatics modeling development providing the basic
morphology, anatomy and organization of the to-be-replaced
tissue on which the pertinent biological design intents can
be introduced. Construction of a Bio-CAD model for a
specific tissue starts from the acquisition of anatomic data
from an appropriate medical imaging modality. This is
referred to as image-based Bio-CAD modeling in which the
imaging modality must be capable of producing
three-dimensional views of anatomy, differentiating
heterogeneous tissue types and displaying the vascular
structure and generating computational tissue models for
other down stream applications, such as analysis and
simulation. The developed CAD models can be stored in
various format and used for a variety of different design
applications. For example, the reconstructed femur bone can
be used to design patient specific hip implants using CAD
soft ware. CAD models can also be used for dynamic force
analysis using CAD based software. An image based
bio-CAD modeling process involves the following three
major steps:
(i) Non-invasive image acquisition
(ii) Imaging process and three-dimensional reconstruction
(3DR)
(iii) Construction of CAD-based model
5. NON-INVASIVE IMAGE ACQUISITION
The CAD model can be developed from CT/MRI [6, 7]
image through a number of different process paths. CT or
Computer Aided Design of Scaffolds for Tissue Engineering Applications
micro-CT scans involves the exposure of a sample to small
quantities of ionizing radiation, the absorption of which is
detected and imaged resulting a series of 2D images.
Stacking these images creates a 3D representation of the
scanned area. The recent development of micro-CT
technology has been successfully used in various fields such
as to quantify the micro structure function relationship of
tissues and the designed tissue structures, including the
characterization of micro-architecture of tissue scaffolds [8,
9], to design and fabricate engineered tissue microstructures
[10, 11], to quantify the bone tissue morphologies and
internal stress-strain behavior [12, 13], to evaluate the porous
biomaterials [14], and to model lung tissue at high resolution
[15]. The main advantage of CT and micro-CT as an imaging
modality for tissue engineering is reasonably high resolution.
MRI provides images for soft tissues as well as for hard
tissues and as such is vastly superior in differentiating soft
tissue types and recognizing border regions of tissues of
similar density. Though MRI has the high tissue
differentiation capacity, the resolution is consistently worse
than CT and optical microscopy. MRI has more clinical
applications because it does not expose the patient to
ionizing radiation. Further, a hybrid modality approach may
be effective for determining a more precise 3D model on
the same specimen to correct for deficiencies in any single
modality. For example, 3D models derived from MRI and
CT could be combined to display heterogeneous soft tissue,
for which MRI is excellent, within a high-resolution bone
structure such as the skull, for which CT is better suited. A
combination of CT and PET has been studied as a means to
provide both structural and metabolic information for
clinical applications such as precise localization of cancer
in the body [16]. A CT/optical microscopy combination
might be of use in correcting the histological distortion from
the physical sectioning required for optical microscopy.
6. IMAGING PROCESS AND THREE-DIMENSIONAL
RECONSTRUCTION (3DR)
The image process and the three dimensional reconstruction
can be used for volume rendering, volumetric representation
and three-dimensional image representation. These 3-D
images lead to the generation of anatomic modeling which
is used for contour based generation and 3D shaded surface
representation of the CAD based medical models. Some of
the visualization issues that cannot be resolved by CAD
models provide motivation for the construction of a
prototype model. Prototype modeling is done through
additive or constructive processes. 2D segmentation is
extraction of the geometry of the CT scan data set [17]. 3D
segmentation [18] of the CT data set are able to identify,
within the CT data set, voxels bounding the bone and extract
a ‘tiled surface’ from them. The most popular algorithm is
the marching cube algorithm [19, 20]. The marching cube
method produces tiled surfaces with missing triangles with
a large number of triangle elements. This method decom-
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poses the complex geometries in ‘finite elements’ and
approximations to the behavior of the system and the quality
of approximation depends on the number of these elements
and the order of the approximation over each element. In
the visualization processing, each triangle is treated as
separated polygonal entity and the computational requirements scale up exponentially with the number of triangles.
To overcome these difficulties, a new algorithm, Discretized
Marching Cube (DMC) algorithm has been developed for
the 3D segmentation of the CT data set which may be able
to resolve most topological inconsistencies and maintaining
a high level of geometric accuracy through implementing
various disambiguation strategies.
7. CONSTRUCTION OF CAD BASED BIOMODELING
The non-invasive modalities, such as CT, Micro- CT, MRI
and Optical Microscopy can be used to produce accurate
3D tissue descriptions, but the voxel-based anatomical
imaging representation cannot be effectively used in many
biomechanical engineering studies. For example, 3D surface
extraction requires a large amount of computational power
or extreme sophistication in data organization and handling,
whereas 3D volumetric model used to produce a realistic
3D anatomical appearance, does not contain geometric
topological relation. Further both the techniques are not
capable of performing anatomical structural design,
modeling-based anatomical tissue biomechanical analysis
and simulation. In general, activities in anatomical modeling
design, analysis and simulation need to be carried out in a
vector-based modeling environment, such as using
Computer-Aided Design system and CAD-based solid
modeling, which is usually represented as ‘boundary
representation’ (B-REP) and mathematically described as
Non-Uniform Rational B-Spline (NURBS) functions.
Unfortunately, the direct conversion of the medical imaging
data into its NURBS solid model is not a simple task. In the
last few years some commercial programs, for example,
SurgiCAD by Integraph ISS, USA, Med-Link, by Dynamic
Computer Resources, USA, and Mimic and MedCAD, by
Materialise, Belgium, were developed and used to construct
CAD-based model from medical images. However, none
of these programs has been efficiently and widely adopted
by the biomedical and tissue engineering community due
to the inherent complexity of the tissue anatomical
structures. Effective methods for the conversion of CT data
into CAD solid models still need to be developed.
8. ORGAN PRINTING
Organ printing is a biomedically relevant variant of rapid
prototyping technology which is based on tissue fluidity and
involves the computer-assisted deposition of cells or matrix
is done at a time until a 3D form is obtained. The rapid
prototyping techniques which are currently used to design
solid synthetic scaffolds [21, 22] are not capable to place
cells or cell aggregates into a printed scaffold. To overcome
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International Journal of Computational Intelligence and Healthcare Informatics
the limitation of the present technique, organ printing is
becoming more important for the design of scaffold which
is based on using layer by layer deposition of cell and/or
cell aggregates into a 3D gel with sequential maturation of
the printed construct into perfused and vascularized living
tissue or organ. The organ printing technique have different
printer designs and components for the deposition process
such as Jet-based cell printers, cell dispensors or bioplotters,
the different types of 3D hydrogels and varying cell types.
The organ printing process consists the following three
steps(i) Preprocessing
(ii) Processing
(iii) Postprocessing.
Preprocessing involves the development of a computeraided design (CAD) or blueprint of a specific organ. The
design can be derived from digitized image reconstruction
of a natural organ or tissue. Imaging data can be derived
from various modalities including noninvasive scanning of
the human body such as magnetic resonance imaging (MRI),
computerized tomography (CT) or a detailed 3D
reconstruction of serial sections of specific organs. [23]
Another approach to designing of tissue scaffold was
developed by Karch et al which is known as constrained
constructed optimization (CCO), which is based on
mathematical modeling using a set of theoretical principles
related to spatial organization [24]. Processing usually refers
to actual computer-aided printing or layer by- layer
placement of cells or cell aggregates into a 3D environment
using CAD or blueprints and postprocessing is concerned
with the perfusion of printed organs and their biomechanical
conditioning to both direct and accelerate organ maturation.
9. CONCLUSION
This paper was intended to explore the Computer aided
tissue engineering techniques for the systematic design of
scaffold. Solid freeform fabrication, image based bio-CAD
modeling, imaging and three dimensional reconstruction,
organ printing were found to be effective for designing and
manufacturing of complex tissue scaffold which can be used
as the extra cellular matrix for neo tissue or cell growth to
replace or repair damaged or diseased tissue or organ. So it
is evident that the various CATE techniques can be used to
design the scaffold in future.
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