3D printed scaffold could free diabetic cell transplant recipients from immunosupressive meds

Islet cell transplantation has been used to treat Type 1 diabetes since the early 1990s​ with varying degrees of success. While new surgical protocols​  have helped, the success rate for such procedures is still low.

Aside from donor cell availability, the major challenge is that transplanted cells will be attacked by the recipient's immune system unless the patient is treated with immunosupressive, anti rejection drugs according to Diabetes UK spokesman, Richard Elliott.

“As of 2013, 95 islet transplants had been performed in 65 people in the UK. However, the process is not perfect – strong anti-rejection medication is required​."

But this requirement could change according to Aart van Apeldoorn and colleagues at the University of Twente, who suggest that a 3D printed alginate-gelatin scaffold could be used to protect trasplanted cells and free diabetics from a lifetime of immunosuppressants.

Van Apeldoorn told us "Many research groups are using alginate droplets for encapsulation of islets  to create an immunoprotective barrier between the host immune cells and the donor cells. Addition of gelatin doesn’t not interfere with this principle.​

"The reason for adding gelatin to alginate is that printing with alginate alone is not possible since the viscosity of the non-crosslinked alginate is way too low to allow for a 3D macroporous structure to be printed" ​​he explained.

Van Apeldoorn also suggested that: "Assuming the scaffolds are stable over a long time period, they could prevent the donor islets being destroyed by the host immune cells without the need for immunosupressive drugs​."

Targeting​

In addition to protecting the cells against recipient immune response, the gelatin alginate scaffolds will also prevent transplanted cells from migrating according to Van Apeldoorn.

“Our results showed that once the islet cells were retrieved from the alginate/gelatin scaffolds in the lab they were able to produce insulin and respond to glucose in the same way as non-printed islet cells, indicating that the procedure had not affected their viability or function at all.​

“The macroporous scaffolds also ensured that the islet cells would not migrate uncontrollably through the body once transplanted into the donor site​.”

Optimisation​

The next stage of the process is to optimise the environment within the scaffolds as Van Apeldoorn explained.

"We discovered that by adding gelatin to the alginate the diffusion of insulin and possibly other biological factor is hindered. Beta cells, which are producing and secreting insulin continuously  are highly metabolic active cells and require a very efficient and good supply of nutrients and oxygen to function properly.​

"One goal should be to focus on an ideal combination of biomechanical and mass transport properties to be able to create porous 3D hydrogel scaffolds, which can protect the islets, but allow for ideal diffusion of nutrients and oxygen to the encapsulated cells. ​

"Another interesting goal could be to create the ideal biomimetic environment for the encapsulated islets. It has been shown by several authors that specific proteins in the islets extracellular microenvironment can have a beneficial effect on either beta cell function, survival or proliferation​."

The team is also assessing the feasability of inserting immunomodulatory molecules into the scaffold to dampen the inflammatory response to the implanted cells.

Source: ​Biofabrication​​ ​

“Fabrication of three-dimensional bioplotted hydrogel scaffolds for islets of Langerhans transplantation​”

G Marchioli, L van Gurp, P P van Krieken, D Stamatialis, M Engelse, C A van Blitterswijk, M B J Karperien, E de Koning, J Alblas, L Moroni and A A van Apeldoorn​

DOI:  10.1088/1758-5090/7/2/025009​​​