Jul 3, 2018 | By Thomas

Researchers at the University Medical Centre (UMC) Utrecht in the Netherlands are working to make 3D bioprinted tissues that can be implanted into a living joint affected by arthritis.

Arthritis is an inflammation of the joints, and it can affect one joint or multiple joints. Out of every 100,000 people, 41 are diagnosed with arthritis every year. Arthritis causes discomfort and pain and makes everyday tasks difficult.

As part of a project called 3-D-JOINT, Professor Jos Malda at the UMC Utrecht in the Netherlands and his team are currently developing bioprinted tissues that can be implanted into a living joint to replace the damaged part. These would eventually mature into a tissue that is the same as the original healthy cartilage.

While it’s possible to 3D print stem cells according to a precise blueprint, that doesn’t mean that they can instantly transform into new organs or body parts.

"Printing is not the last step in biofabrication, since printing something in the shape of a heart does not make it a heart," said Prof. Malda. "The printed construct needs time and the correct chemical and biophysical cues to mature into a functional tissue."

Professor Jos Malda

One challenge is maintaining the right conditions for the cellular building material. Because bioinks contain living cells, it is not solid enough to keep shape after printing. Scientists are having to develop new solutions, and one option is to use a hydrogel—a type of material that consists of networks of large molecules known as polymers, swollen with water.

“For bioprinting, the material has to be able to keep cells alive,” Professor Malda explained. “This demands aqueous conditions and processing under a relatively low temperature, which makes hydrogel-based materials ideal candidates.”

But hydrogels are soft enough to deliver cells, they are unable to withstand the mechanical load certain tissues undergo in the body. To solve that, Prof. Malda and his team have been experimenting with additive materials, which can make the hydrogels strong enough to act as replacement cartilage.

"Reinforcing the hydrogel makes it stronger – just like steel rods are combined with soft cement to create the reinforced concrete that makes the foundations of our homes," said Prof. Malda.

His team is using a 3D printing technique called melt electrowriting, which combines melted polycaprolactone, a type of polyester, with an electrical field that creates fibres as thin as a hair. Using these microfibres, the team creates scaffolding to be combined with the cell-containing hydrogel – already with good results.

"The combination of the hydrogel with the fibres acts in synergy, increasing the strength of the composite over 50 times while still allowing the cells to generate extracellular matrix and mature into a cartilage-like tissue," Prof. Malda said.

His team is working on upscaling that process to create larger constructs, while bringing together different materials for combined bone and cartilage tissue replacements. In addition to acting as a replacement for lost cartilage and bone, printing cells in this way can also help the body to repair damaged tissues.

Professor Daniel Kelly at Trinity College in Dublin, Ireland, is working as part of a project called JointPrinting to develop such a system.

"There are relatively few examples in the literature demonstrating the capacity of bioprinted tissues to actually regenerate damaged tissues in appropriate pre-clinical (animal) models," Prof. Kelly said.

He is working to develop bioinks that are not only printable but which also spur stem cells to make new cartilage by altering the molecules that support and surround the printed cells, instructing them to generate the correct type of tissue. The goal is that these newly printed stem cells can help repair damaged tissue after they are implanted in the body.

The team is also working with using substances known as growth factors to stimulate the formation of new blood vessels in injured tissues. "We sometimes incorporate VEGF (vascular endothelial growth factor) into our bioprinted tissues … to encourage new blood vessels to form in regions of a damaged bone or joint where we want bone to grow," he said.

"We introduce gradiants of VEGF into the bioprinted tissues that directs host blood vessels (to form) into the appropriate regions of our implants."

Though scientists are focusing on cartilage and bone, demands on joints can differ dramatically depending on where they are located in the body.

To test the printed tissues, Prof. Kelly uses specialised mechanical testing machines to determine their stiffness and elasticity, as well as computational modelling to better understand how the structure and composition of the implants can be tuned to function within specific environments.

"I think bioprinting will have two main applications. Firstly, as a source of new tissues and organs in regenerative medicine. Secondly, as a tool to better understand human disease and to test the safety and efficacy of new drugs targeting such diseases," said Professor Kelly.



Posted in 3D Printing Materials



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