Mar.6, 2014 | By Julie Williams

3D-bioprinting is an exciting new technology, which may one day lead to the fabrication of replacement human tissues on-demand for transplantation. A team of scientists at Swansea University in the UK are working on the design and development of a new generation 3D-bioprinting technology, together with the biological methods to make living tissues. With development then there is hope that this process can be used to make living constructs that can be used to replace damaged or diseased tissues. This is being focused towards producing lost tissue of the knee or hip as a result of arthritis and for such applications as abdominal, tracheal and breast reconstruction following cancer. This next step in the development of this process could one day transform the field of reconstructive medicine.

The research group at the University's College of Medicine is developing the technology that is used to fabricate these living structures. The latest version of 3D-bioprinter developed is the 3Dynamic Tissue Engineering Workstation, which makes this complex process accurate, reliable and more accessible. Dr. Daniel Thomas of the University's College of Medicine who works on this research explains,

"This method of 3D-bioprinting has been developed to allow for a wider proliferation of the technology, allowing experimentation at a both a University and clinical level. This approach should see a greater adoption of this technology and further innovation in the short-term by enabling researches in the field to effectively produce tissue."

Swansea Universities experimental 3Dynamic Tissue Engineering Workstation, which is being used to produce chondrocyte-based tissues such as vertebrate trachea sections.

When the research was started two years ago, there was no such thing as a 3D-bioprinter that could make a soft tissue, so the Swansea team designed and then built one specifically around the material properties itself. This was specifically engineered to produce tissues that are made from Chondrocyte cells, which produce and maintain the cartilaginous matrix in some of the body's tissues. These cells are bioprinted into the shape of a 3D biological architecture, such as a trachea. This is done with the appropriate precision to duplicate its structural complexity. The evolution of this process as a viable technology has firstly focused on developing the 3D-bioprinting hardware, firmware and software capability. This element of the technology directly stems from innovations made in conventional 3D Printing. This is concurrently developed with research which incorporates aspects of cellular self-organisation, developmental biology and tissue maturation processes, in order to make complex living structures.

3D-bioprinting used to generate heterogeneous tissues using a mixture of; chondrocytes cells, alginate, hyaluronic acid, transforming growth factor ß1, antibiotics and gelatine to form a printable bioactive gel which matures into a tissue.

This research is currently specialising in producing useful living materials for knee repair. Patients with arthritis of the knees due to the wear of articular cartilage can current at best hope for an arthroplasty operation, which involves the installation of an artificial knee joint. This is a painful procedure that is not necessarily permanent. Using 3D-bioprinting, patches of tissue can be firstly fabricated and then used for transplantation thus allowing for the knee cartilage to be repaired. The global knee replacement market was worth $6.9 billion in 2010, and due to our aging population will reach $11 billion by 2017. The 3D-bioprinting research at Swansea University focuses on building simple living tissues for use in this type of reconstructive surgery, to directly benefit these patients. "Our research is specifically being used to explore the possibility of using this technology to make biological structures that can be used to replace damaged or lost cartilage of the knee" says Daniel.

As with conventional 3D-Printing technologies, this research focuses on developing fully digital machines which are more effective at depositing complex biological-based fluids. "3D-bioprinting is essentially a conventional layer-by-layer automated additive deposition process that is used to fabricate three-dimensional functional living macro tissues" Daniel explains. "This process has to be computer numerically controlled in order to ensure the precise deposition of a bioactive gel which is deposited as a build material. There is also the need to account for the self-organising properties of cells in order to produce a functional tissue which has measurable biological, mechanical, metabolic and functional properties."

The 3D-bioprinting processes works by first loading a syringe-based deposition system with a biologically active gel containing between 2 and 20 million chondrocyte cells per millilitre, together with alginate, hyaluronic acid, growth factor β1, antibiotics and gelatine. A control software which is based on a pronterface architecture is used to instruct stepper motors attached to each axis to position the head in xyz coordinates. This allows for the fabrication of a tissue structure to a ±5µm degree of precision, just like a conventional 3D printing system. As the tissue is bioprinted, the deposition speed is altered in-situ to ensure that the tissue resolution is maintained.

When a bioprinted pre-tissue is transferred to a 37.8°C temperature bioreactor with growth factor replaced every two days then cells begin to grow and mature into a tissue matrix over a period of three weeks. Critically, 0.1% hyaluronic acid is added to the biogel to limit the loss of proteoglycans during tissue maturation. As Daniel explains "This is important as proteoglycans are a critical component of extracellular matrix. This filler material exists between the cells of a tissue and makes the structural and biochemical support to the surrounding tissue, without it then a tissue doesn't form correctly".

Structures currently produced using the 3D-bioprinting process including a palate, ear structures and simplified trabecular bone geometry.

By varying the deposition speed, the layer resolution can be altered. Additional methods using multiple biomaterials can also be used to integrate printed tissues with 3D scaffold fabrication. Various hydrogels-based materials can be used for depositing a scaffold, including fibrin, Poly (lactide-co-glycolide) which is porous, agarose, and alginate. This could be a way of making replacement arteries. The challenge of this research is in understanding the underlying interactions between 3D cellular structures and appropriate scaffold materials for producing living tissues. In order to overcome these limitations, new methods to precisely deposit cells and scaffolds together are being developed by the team.

In the longer term, the ultimate aim of this research is to develop bioprinting as a process that can be used to produce multiple tissue types to act as operative repair materials or in the short-term for pharmaceutical testing. With further engineering work this can enable the simultaneous deposition of different cell types including stromal stem cells, cardiomyocytes, progenitor cells, osteoblasts and osteocytes to produce complex tissues. Daniel explains "Different stem cellular-based materials can be deposited to produce complex tissue structures for such applications as abdominal and for breast reconstruction. To continue this theme, we are currently investigating the process of producing components of the ear, such as the helix, which is important in giving the ear its structure." Further advances in this field may also lead towards direct intra-operative applications in which innovative engineered tissues are 3D-bioprinted directly into a patient. This means of producing tissue within a clinical environment in vivo has the potential to revolutionise treatment for patients.



Posted in 3D Printing Technology


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Alan Cheng wrote at 3/10/2014 1:23:32 PM:

@alidan - I don't think so as this machine is two years old and was built before kickstarters Eventor bot was even started. The last I heard was that the Eventor bot failed to materialise because the guy didn't finish the project and a lot of people didn't get their machines.

alidan wrote at 3/10/2014 12:53:25 AM:

is that an Eventorbot?

George Jackson wrote at 3/7/2014 8:28:29 PM:

Wow, this is really fascinating, shows yet another example how science may one day be able to make a really transform and improve lives.

Leslie Hulling wrote at 3/7/2014 11:12:29 AM:

This is really interesting, hopefully one day this technology will bring hope to many who may need a new piece of tissue, there are just so many possibilities and applications.

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