3D Bioprinting Research Could Result in Replacement Cartilage for Curing Arthritis

One out of ten people will suffer from arthritis in their lifetime. Arthritis is caused by the breakdown of the cartilage tissue in a person’s joints. This breakdown leads to swelling, stiffness, discomfort, and pain. Increasingly, researchers have been looking into bioprinting to 3D print replacement cartilage using patients’ own stem cells in order to get a damaged joint to heal itself, which would effectively end arthritis.

As part of the 3D-JOINT Project, funded by the European Commission’s Horizon 2020 framework, Professor Jos Malda with the University Medical Centre (UMC) Utrecht in the Netherlands and his team are developing bioprinted tissues that can replace a damaged part once implanted into a living joint. These bioprinted replacement tissues will eventually mature into a match for the original, healthy cartilage.

While it’s possible to 3D print stem cells layer by layer to make complex tissues, like knee cartilage, that doesn’t mean that they instantly become viable body parts and organs. It’s critical to keep the correct conditions for cellular building material, which is obviously trickier to deal with than plastic.

Professor Jos Malda

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

Bioinks contain living cells, and some scientists use hydrogels, which consist of water-swollen polymer networks, to help the process.

“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.”

Hydrogels are soft enough to deliver cells, but are not able to hold up under the same mechanical load that certain tissues do in the human body. So Professor Malda and his team have been experimenting with additive materials, which strengthen the hydrogels so they can be effective replacement cartilage.

Professor Malda said, “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.”

The UMC Utrecht team is using a 3D printing technique known as melt electrowriting, which combines a melted form of a polyester called polycaprolactone with an electrical field. This process creates extremely thin microfibers, which are then used to create scaffolding that is merged with the cell-containing hydrogel.

Professor Malda said, “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.”

The team, with a goal of eventually 3D printing a complete joint, is enjoying favorable results, and is now working to scale up the process in order to create larger constructs; in addition, they’re working with different materials for combined bone and cartilage tissue replacements.

But using bioinks to make replacement cells for bone and cartilage isn’t the only benefit of 3D bioprinting for arthritis treatment. Professor Daniel Kelly from Ireland’s Trinity College Dublin, who has researched using 3D printing to repair bone before, is working on the JointPrinting project to develop a system that can repair damaged tissues in the body.

Professor Kelly said, “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.

“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.”

Professor Kelly and his team are developing 3D printable bioinks that, by changing the molecules which support and surround printed stem cells, will encourage them to produce new cartilage – essentially teaching them how to make the right tissue type. The goal here is to make 3D printed stem cells that will be able to fix damaged tissue once they have been implanted in a person’s body.

The team is also using growth factors to stimulate new blood vessels to form in injured tissues.

Professor Kelly explained, “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.

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

The demands on human joints can be very different, depending on where in the body they’re located. To test his team’s 3D printed tissues, Professor Kelly uses computational modeling to get a better idea of how the implants’ composition and structure can be fine-tuned in order to function within different environments. He also finds their elasticity and stiffness through specialized mechanical testing machines.

Hopefully, it won’t be too long before 3D bioprinting can be used to find a quick, effective treatment for painful arthritis.

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[Source: European Commission / Images UMC Utrecht unless otherwise noted]