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|Title: ||Systems for the automated 3D assembly of micro-tissue and bio-printing of tissue engineered constructs|
|Authors: ||Lang, Michael|
|Issue Date: ||2012|
|Abstract: ||Tissue engineering is a field devoted to the design and creation of replacement
tissues with the ultimate goal of one day providing replacement organs. Traditional
strategies to accomplish this through the bulk seeding of cells onto a single
monolithic porous bio-scaffold are unable to realise a precise architecture, thus
the inability to mimic the cells natural micro-environment found within the body.
Bio-printing approaches are the current state of the art with the ability to
accurately mimic the complex 3D hierarchical structure of tissue. However, a
functional construct also requires high strength to provide adequate support in
load bearing applications such as bone and cartilage tissue engineering, and to
maintain the open geometry of a large intricate channel network, which is crucial
for the transport of nutrients and wastes. Typical approaches utilise materials
which have processing parameters more amendable for cell incorporation, thus
they can be simultaneously deposited with scaffolding material. However, the
resulting construct is typically of low strength.
This thesis explores the automation of a printing and “tissue assembly” process
with the ability to incorporate delicate cell aggregates or spheroids within a high
strength bio-scaffold requiring harsh processing parameters, at precise locations.
The 3D printed bio-scaffold has a lattice architecture which enables a frictional fit
to be formed between the particle and scaffold, thus preventing egress. To achieve
this the pore must be expanded before the delivery of a single 1mm particle.
Novel subsystems were developed to automate this process and provide the ability
to achieve scalable, flexible, complex constructs with accurate architecture.
A system architecture employing the benefits of modularity was devised. The
main subsystems developed were the singulation device, to ensure the separation
of a single particle; the injection device, to deliver and seed particles into the
scaffold, and the control system, to facilitate the operation of the devices.
Three generations of singulation devices have been developed ranging from
mechanical to fluid manipulation methods alone. The first prototype utilised
mechanical methods, with simple control methods. However the inability to
correctly position the lead particle within the singulation chamber, resulted in
damage to the test alginate particles. In the second prototype a fully fluidics based
device utilised two trapping sites to capture the leading particles. Singulation
success rates of up to 88% was achieved. Higher rates were limited by the trapped
particle’s interaction with the lagging particles during capture. In a similar
concept to the second prototype, the third prototype utilised only a single trapped
particle, and achieved much higher throughput, and 100% singulation accuracy.
The injection device, utilised a conical expanding rod within a thin outer
sheath. It was able to expand the pore, with minimal damage to the scaffold,
providing an unobstructed path for the delivery of the particle into the pore.
A decentralised control system was devised to integrate the process operation
for the electro-mechanical devices. Separate microcontrollers were able to sense,
interact and communicate with one another, and the master control PC, to execute
specific tasks to automate the process.
The development of systems to automate the process has addressed the
ability to accurately incorporate delicate cells with a high strength bio-scaffold,
and will enable the realisation and investigation of intricate complex constructs,
unachievable with current manual processes. Thus features found within the
body may be more closely mimicked and functionalised, which may provide the
necessary signals, micro-environment and infrastructure to correctly regulate the
formation of complex functional tissue, supported by the adequate mass transport
of nutrients and wastes. This may one day lead to 3D printing or assembly of
viable replacement tissue, accurate in vitro model systems for laboratory testing,
or even whole organs.|
|Publisher: ||University of Canterbury. Mechanical Engineering|
|Degree: ||Master of Engineering|
|Rights: ||Copyright Michael Lang|
|Rights URI: ||http://library.canterbury.ac.nz/thesis/etheses_copyright.shtml|
|Appears in Collections:||Theses and Dissertations|
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