Researchers at Wake Forest University School of Medicine have developed a 3D-printing method that could help overcome a major barrier to developing cell-based treatments for Type 1 diabetes: keeping insulin-producing cells healthy and functional.
In laboratory testing, donated human pancreatic islets – or clusters of pancreatic cells – embedded within the 3D-printed tissue remained viable and responsive to glucose for 21 days. By comparison, islets maintained using conventional laboratory culture methods showed a significant decline in function.
The findings recently published online in Acta Biomaterialia.
Pancreatic islets produce insulin and other hormones. Type 1 diabetes develops when the immune system destroys the insulin-producing beta cells within these islets, preventing the body from properly regulating blood sugar.
Most people with Type 1 diabetes manage the condition with insulin therapy and using technology to monitor blood sugar levels. Transplanting healthy pancreatic islets can restore insulin production in some patients, but the treatment is not widely available. Barriers include a shortage of donated islets, poor survival of transplanted cells and immune rejection.
“Our goal was to create an environment that more closely resembles the pancreas and helps these delicate cells remain viable,” said Amish Asthana, Ph.D., assistant professor of surgery and regenerative medicine at Wake Forest University School of Medicine and corresponding author of the study. “Pancreatic islets are extremely sensitive and can quickly lose their ability to produce insulin.”
Engineering a pancreas-like environment
For the study, researchers used a specialized 3D printer to create tissue-like structures containing donated human pancreatic islets. The islets were printed within a soft gel, called a bioink, designed to provide a supportive environment for the cells.
The bioink combined alginate, a material derived from seaweed, with material obtained from donated human pancreatic tissue. The donated tissue was processed to remove living cells while preserving the proteins and structural components that naturally support cells in the pancreas.
Researchers also adjusted the printing process to reduce stress on the islets.
After printing, more than 85% of the islet cells remained viable. The cells also continued releasing insulin in response to changing glucose levels throughout the 21-day study.
The islets remained functional even when printed at a clinically-relevant, high concentration. That finding could be important if the approach is eventually used to produce cell-based treatments.
“The encouraging result is that the islets remained healthy and responsive to glucose for three weeks, even at a high concentration,” said Asthana, who conducts his research at the Wake Forest Institute for Regenerative Medicine. “This suggests that material derived from the pancreas may provide the kind of support these cells need to maintain their function.”
Laboratory testing also showed that while nutrients and other small substances could easily pass through the printed material, the gel effectively blocked larger molecules. The researchers noted this feature could act as a physical barrier against immune system antibodies, potentially helping to shield the cells from rejection after transplantation. However, researchers also noted these findings need further evaluation.
Building on the early findings
The findings provide an encouraging foundation for continued development of the 3D-printed tissue. Because this study focused on how the donated human islets performed in the laboratory, researchers are currently evaluating the approach in preclinical models of diabetes.
"We are testing whether the printed tissue can remain functional after transplantation, develop a blood supply and help regulate blood sugar,” said Sang Jin Lee, Ph.D., professor at the Wake Forest Institute for Regenerative Medicine. “We are also studying how it interacts with the immune system, including whether the material could eventually help protect transplanted islets from rejection.”
Although additional research is needed before the technology could be tested in people, the findings suggest that 3D-printed pancreatic tissue may be a promising platform for developing future cell-based diabetes therapies.
“Advances in 3D bioprinting are poised to fundamentally transform the way we think about and practice transplantation, moving the field from donor organ replacement toward the on-demand fabrication of living, patient-specific tissues and organs,” said Giuseppe Orlando, M.D., Ph.D., professor of surgery and transplant surgery at Wake Forest University School of Medicine.
The authors reported no conflicts of interest.
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About Wake Forest University School of Medicine
Wake Forest University School of Medicine is the academic core of Charlotte, North Carolina-based Advocate Health and a recognized leader in experiential medical education and groundbreaking research. It directs the education of nearly 1,900 students and fellows, including physicians, basic scientists and allied clinical professionals. The school of medicine also strategically investigates opportunities that will expand basic and clinical research, resulting in nationally and internationally recognized excellence in biomedical research. The school has two campuses, each co-located with leading-edge innovation districts, The Pearl, in Charlotte, and Innovation Quarter, in Winston-Salem, North Carolina. These affiliated life-sciences innovation districts focus on advancing health care through new medical technologies and biomedical discovery.
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