3D Bioprinting and Translation of Beta Cell Replacement Therapies for Type 1 Diabetes.

Abstract

Type 1 diabetes (T1D) is an autoimmune disorder in which the body's own immune system selectively attacks beta cells within pancreatic islets resulting in insufficient insulin production and loss of the ability to regulate blood glucose (BG) levels. Currently, the standard of care consists of BG level monitoring and insulin administration, which are essential to avoid the consequences of dysglycemia and long-term complications. Although recent advances in continuous glucose monitoring and automated insulin delivery systems have resulted in improved clinical outcomes for users, nearly 80% of people with T1D fail to achieve their target hemoglobin A1c (HbA1c) levels defined by the American Diabetes Association. Intraportal islet transplantation into immunosuppressed individuals with T1D suffering from impaired awareness of hypoglycemia has resulted in lower HbA1c, elimination of severe hypoglycemic events, and insulin independence, demonstrating the unique potential of beta cell replacement therapy (BCRT) in providing optimal glycemic control and a functional cure for T1D. BCRTs need to maximize cell engraftment, long-term survival, and function in the absence of immunosuppression to provide meaningful clinical outcomes to all people living with T1D. One innovative technology that could enable widespread translation of this approach into the clinic is three-dimensional (3D) bioprinting. Herein, we review how bioprinting could facilitate translation of BCRTs as well as the current and forthcoming techniques used for bioprinting of a BCRT product. We discuss the strengths and weaknesses of 3D bioprinting in this context in addition to the road ahead for the development of BCRTs. Impact statement Significant research developments in beta cell replacement therapies show its promise in providing a functional cure for type 1 diabetes (T1D); yet, their widespread clinical use has been difficult to achieve. This review provides a brief overview of the requirements for a beta cell replacement product followed by a discussion on both the promise and limitations of three-dimensional bioprinting in facilitating the fabrication of such products to enable translation into the clinic. Advancements in this area could be a key component to unlocking the safety and effectiveness of beta cell therapy for T1D.