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.

Bioengineering the Vascularized Endocrine Pancreas: A Fine-Tuned Interplay Between Vascularization, Extracellular-Matrix-Based Scaffold Architecture, and Insulin-Producing Cells

“…3D-bioprinted constructs designed for β-cell replacement should follow this strategy by creating channel or tubular architectures. Several bio-fabrication protocols have proposed different approaches for this purpose: use of coaxial nozzles to obtain hollow tubular strands; introduction of sacrificial polymers in extrusion-based bioprinting, such as Pluronic F127 or gelatin, which can be removed by changing the temperature, pH, or through enzymatic degradation, leaving hollow structures; and fabrication of perfusable light-based printed structures, which can be embedded in the 3D printed scaffolds (22,25,(204)(205)(206)(207). All these structures can be in vitro re-endothelialized to recreate a functional vasculature using a medium flow connected to a perfusable system, allowing a dynamic culture.…”

An Overview of Engineered Hydrogel-Based Biomaterials for Improved β-Cell Survival and Insulin Secretion

“…For having high metabolic activity, β -cells should receive high nutrition and oxygen. Thus, fabrication of engineering macrosystems transferring enough nutrition and oxygen to the cells is of great importance for designing this kind of system ( Gurlin et al, 2020 ).…”

Tissue Engineering Strategies for Improving Beta Cell Transplantation Outcome

“…Vascularized tissue was observed around the sheets day 7 post-implantation. Glycaemia was restored up to100 days [106] insulin-producing cell clusters encapsulated in different biomaterials [140]. The most common 3D bioprinting methods are (1) inkjet bioprinting, (2) microextrusion-based bioprinting, (3) laser-based, and (4) light-based bioprinting.…”

“…Coaxial bioprinting is also a type of the extrusion bioprinting, which allows co-printing of two biomaterials, each containing different types of cells. More detailed information about each method is discussed in these review articles [12,140]. Marchioli et al were the first to bioprint directly beta cells and islets mixed with a hydrogel.…”