An
international team of researchers at the Materials Processing
Research Centre (MPRC) of Dublin City University (DCU) has just
begun exciting work on innovative methods of producing hard and soft
tissue substitutes. The long term aim is that these materials
replace parts of human bone or human arteries in the case of disease
or trauma.
The European Commission
funded project, costing approximately €1.2 million is coordinated by
Dr Lisa
Looney, Director of the MPRC, and senior lecture in the School
of Mechanical and Manufacturing Engineering. Other MPRC lead
investigators are Dr Garrett
McGuinness, Dr Joseph
Stokes and Dr Dermot
Brabazon. They are also collaborating with the vascular health
research centre, and with engineers in ITT Dublin. The research is
being funded under the EU’s Marie Curie Early Stage Training (EST)
programme, and will be implemented by seven postgraduate level
researchers over the next 3 years. These highly qualified young
researchers have been recruited from across Europe (Poland, Spain 1,
Hungary (2)) and further a field (Turkey and China), and from a
range of disciplines (mechanical, biomedical and industrial
engineering, biology and biotechnology) There are several
circumstances under which it is necessary to replace human tissue,
either on a permanent or temporary basis. The current ‘gold
standard’ in replacing both bone and vascular tissue is to use
autografts (material from other sites in the patient), but this can
be problematic. Tissue may not be available and the ‘double’
procedure incurs higher risk of infection, pain and prolongs
hospital stays. Synthetic alternatives do exist, but have not found
widespread application due to difficulties in producing the optimum
material structure and properties, in a repeatable and controllable
manner. Tissue engineering in general aims to
produce patient specific biological substitutes to overcome the
limitations of traditional solutions for damaged tissue, such as
lack of suitable donor organs or diseased cells. The scaffold aids
the delivery of cells when they are implanted and/or provides
temporary mechanical support to newly grown tissue. The advanced
fabrication methods of rapid prototyping technologies and plasma
spraying, may be the key to producing scaffolds with customised and
controllable geometries and internal morphologies. These
characteristics of the scaffold are difficult to achieve using
existing methods, but are important to performance. The project
involves seven Early Stage Researcher (ESR) training programmes and
is led by the Materials Processing Research Centre (MPRC)
situated at Dublin City University (DCU). These are experimentally
based and focus on biomaterial development, processing techniques of
3D printing, photopolymerisation, selective laser sintering and
plasma spraying, structure/mechanical performance, and cell/scaffold
interaction (as described below). The research at DCU will
study a number of innovative manufacturing processes with a view to
achieving this control and repeatability, while characterising the
properties, and response of cells to the tissue substitutes (or
scaffolds).
Novelscaff Group
ESR.1 Irina
Pascu
POWDERED BIO-MATERIALS used in novel techniques
for producing scaffolds
ESR.2 Yurong Liu
PHOTOPOLYMERISABLE HYDROGELS for soft tissue
scaffold applications
ESR.3 Marcin
Lipowiecki
STRAIN BEHAVIOUR of porous graft
structures
ESR.4 Tamas Szucs, Marketa Ryvolova,
Ákos Töttösi
THREE-DIMENSIONAL PRINTING method of hard tissue
scaffold production
ESR.5 Szilvia
Eosoly
SELECTIVE LASER SINTERING production of hard
tissue scaffolds
ESR.6 Diana Garcia-Alonso
PLASMA SPRAYING of free standing hard tissue
scaffolds
ESR.7 Engin Vrana
CELL BEHAVIOUR: Adhesion, Response &
Interaction with Scaffolds
Brief Summary of Results
This programme addressed a series of challenges related to
biomaterials manufacturing processes for implants that are
specifically designed to aid regeneration of bone or blood vessels.
The projects involved the application of a selection of promising
manufacturing technologies to the production of scaffolds with
tightly defined microscale characteristics which are conducive to
the cellular processes involved in tissue regeneration. All of the
technologies involved the use of powdered biomaterials;
Hydroxyapatite (HA, a ceramic) and polycaprolactone (PCL, a polymer)
in the case of bone scaffolds, and polyvinyl alcohol (PVA) and
natural biomacromolecules (such as gelatin) for blood vessel
scaffolds.
For bone scaffolds, a study on the effect of material composition
was performed for porous composites of HA and PCL that were prepared
by a number of methods (salt leaching, phase separation, gas
forming, freeze drying). Based on extensive characterization
experiments, including compatibility with bone cells, the optimum
composites were found to contain 4% HA: 96%PCL, and were formed at a
thickness of 1.2 mm for solvent evaporation, and a thickness of 10mm
for phase separation.
The performance of scaffolds for bone tissue regeneration is also
partly related to how cells attached to the scaffolds deform in
response to both biomechanical loading and biological fluid flow. 3
dimensional images of the honeycomb-like structure of human bone
were obtained using micro-CT scanning, and 3D printing technology
was used to prepare artificial bone samples from powdered materials.
A custom built image analysis system was constructed to study how
strain is distributed in the trabeculae of the porous scaffolds
under compressive loading. A series of permeability tests determined
the fluid transport properties of the scaffolds. The 3D scaffold
printing technology was further investigated using a calcium
phosphate cement (Dicalcium Phosphate Anhydrous/sodium phosphate)
for improved biocompatibility.
Selective laser sintering is a prototyping technology that produces
solid objects with complex three dimensional shapes. It involves the
localized melting of powdered materials by a laser whose focal point
can trace a 3 dimensional path to define the shape of an object. The
energy density delivered by the laser is usually considered
to have the dominant effect on the quality of the structure, but
this study showed that the process is also sensitive to other
parameters such as scan count and part position. Statistical models
have been developed which can better predict the mechanical and
dimensional properties of scaffolds manufactured from HA and PCL
powder blends.
A further set of studies was carried out using a low energy plasma
spray process to deposit free standing samples of HA alone, and in
combination with either PCL or titanium oxide (TiO2).
Statistically designed experiments were used to identify the effect
of three process parameters on sample properties. With porosity
being a restricting characteristic, results point to limited
likelihood that these processes can be used to form bone scaffolds.
The studies on tissue engineered blood vessels resulted in a process
combining the electrospinning process (which produces ultrafine
fibres), photopolymerisation (with an ultraviolet lamp) and
freeze-thaw processes to create blood vessel scaffolds which mimic
the structural characteristics of arteries. The mechanical
compliance of these vessels was similar to arteries under pulsatile
flow conditions. A process for encapsulating smooth muscle cells in
PVA/gelatin gels was developed, ensuring cells are distributed cells
within the scaffold as a precursor to the tissue generation process.
A method for rapidly seeding the surface of the gels with
endothelial cells (found on the inside surface of blood vessels) by
applying a dynamic shear stress was also developed. The ability to
culture both sets of cells simultaneously on the scaffold was also
demonstrated. |
