Researchers from the BIST centre IBEC, in collaboration with IDIBAPS in Barcelona, have developed nontoxic small spheres able to respond to variations in glucose levels and to produce insulin in vitro. The approach has the potential to improve clinical outcomes of β-cell transplantation strategies for diabetes treatment, and for in vitro drug screening platforms.
Diabetes Mellitus is a metabolic disease characterised by a failure in the production of insulin by the β-cells in the pancreas, the hormone responsible for regulating glucose levels in the blood. In 2019, according to the World Health Organization, diabetes caused the death of 1.5 million people worldwide, and there are currently more than 420 million people affected by this disease.
In type 1 diabetes (T1DM), an autoimmune disease, so-called β-cells found in the pancreatic islets, are destroyed by the immune system, avoiding the production of insulin. The most extended treatment in this case is the regular injection of insulin by the patients throughout their lives, to control the persistently high glucose levels in the blood. However, as this therapy does not simulate the real time secretion of insulin by the β-cells, it causes severe chronic complications including cardiovascular diseases and nephropathy.
A promising alternative therapy for T1DM is the transplantation of pancreatic islets containing β-cells. Unfortunately, this cannot currently be done in the clinic due to complications arising from poor oxygenation and vascularisation of the cells, which limit their retention following implantation.
To overcome these obstacles, researchers from the Institute for Bioengineering of Catalonia (IBEC) led by ICREA Research Professor Javier Ramón, Group Leader of the Biosensors for Bioengineering Group, in collaboration with researchers from IDIBAPS, developed a high-throughput methodology applying 3D bioprinting to encapsulate β-cells inside collagen-tannic acid spheroids. This innovative strategy can increase the success of pancreatic islet transplantation and has been published in the Advanced Materials Technologies Journal.
3D bioprinted spheroids containing β-cells produce insulin in vitro
One strategy to increase β-cells retention after transplantation is to use protective semipermeable biomaterials to encapsulate the cells. These engineered tissues, known as spheroids or encapsulated-based microspheres, provide biocompatible properties that confer a more effective cell attachment, thus reducing cell loss, and act as a physical protective barrier against the patient’s immune system.
The new approach proposed by IBEC researchers employs 3D bioprinting technology to develop collagen spheroids crosslinked with tannic acid, in an attempt to mimic the extracellular matrix microenvironment of in vivo β-cells. Crosslinking with tannic acid prevents collagenase degradation, enhances spherical structural consistency, and allows customisation of microsphere diameter with extremely low variability.
To validate the new strategy, researchers prepared 3D collagen-based microcapsules crosslinked with tannic acid containing rat insulinoma cells. They observed that the spheroids maintained cell viability and metabolic activity up to 30 days, reflecting a correct diffusion of oxygen and nutrients. The tannic acid crosslinking strategy also improved the retention of β-cells inside the spheroids.
“Our high-throughput approach facilitates the fabrication of a cell encapsulation system that ensures good survival and functionality of insulin-producing β-cells in a glucose-based manner,” says Laura Clua-Ferré, IBEC researcher and first author of the study.
This novel 3D bioprinting procedure allows for the fabrication of a large number of microspheres capable of responding to glucose by secreting insulin, and can be helpful for advanced functional studies with the goal of β-cell transplantation for diabetes treatment. Additionally, this technology has the potential to open new avenues and be applied to encapsulating a wide range of transplantable cell types.
Learn more on the IBEC website.