Artificial pancreas: what has been achieved so far?

Updated: Aug 10, 2021

Over 400 million people worldwide suffer from diabetes mellitus. The prevalence of diabetes has been steadily increasing for the past three decades and is growing most rapidly in low and middle-income countries, causing millions of deaths [1]. The current treatment for type 1 diabetes (T1D) is exogenous insulin, either through multiple daily injections or continuous subcutaneous insulin infusion (CSII). Despite substantial advances in the treatment of T1D, neither therapy can prevent marked glycemic variability that is associated with an increased risk of hypoglycemia, which requires a higher glucose target to prevent severe hypoglycemic events [2]. Both excessively high and low glucose levels have adverse health effects. Thus, an artificial pancreas can help the patient overcome these problems by taking over glucose control [3].

An alternative to replacing disabled pancreas is an artificial pancreas treatment, also referred to as closed-loop glucose control, a device designed to release insulin as an emerging treatment option combining an insulin pump and continuous glucose monitoring with a control algorithm to deliver insulin in a glucose-responsive manner [4,5]. A continuous glucose monitor to assess blood glucose concentration, a set of glucose control algorithms to calculate the amount of insulin needed, and an infusion pump for insulin administration to lower blood glucose are the critical components of an artificial pancreas [3]. However, a recent critical review investigated potential problematic situations arising through AP use, including confidentiality and data safety that the artificial pancreas’ vulnerability can jeopardize security breaches or unauthorized data sharing. The cost coverage and patient coaching and support are also issues to consider. [6,7].


Figure 1: Artificial pancreas mechanism [2].


A different approach for the repair and replacement of non-functional or damaged organs is the field of tissue engineering and bioprinting, which helps to design biological substitutes. Bioprinting cells in controlled amounts and locations in 3D culture can enable the formation of pancreatic islets with biomimetic composition and improved functionality with further advances allowing for complete pancreas restoration. These islets can be manufactured using different bioprinting techniques [8,9].

Therefore, engineered islets can be fabricated first and then encapsulated during the bioprinting process, in the form of a spheroid, and then deposited into a larger-scale vascularized tissue construct. When spheroids are in contact with each other, they fuse and coalesce into cohesive tissues, creating complex tissues and organs for medical use [10]. The human pancreas produces pancreatic juice surrounded by about 1 million pancreatic islets, tiny beads consisting of alpha and beta cells that produce insulin and glucagon. Michał Wszoła and his team of researchers have collected pancreatic islet cells from mice and pigs and mixed them with bioink to create an organ responsible for the production of insulin. The bioprinter began to arrange the pancreatic cells spatially in the bioreactor. Using a second syringe, simultaneously, researchers printed blood vessels through which the blood would flow in the organ, and they were able to print the organ with a thickness from 1 cm to 1.5 cm. This mechanism aims to create a pancreas ready to cure diabetes, not to repair the native organ, revolutionizing regular diabetes treatments [11].


Process | Credits: Fundacja Badań i Rozwoju Nauki

Figure 2: An ideal process for the manufacture of the artificial pancreas [12].


REFERENCES


1. World Health Organization. Global Report on Diabetes. (World Health Organization, 2016).

2. Nijhoff, M. F. & de Koning, E. J. P. Artificial Pancreas or Novel Beta-Cell Replacement Therapies: a Race for Optimal Glycemic Control? Curr. Diab. Rep. 18, 110 (2018).

3. Blauw, H., Keith-Hynes, P., Koops, R. & DeVries, J. H. A Review of Safety and Design Requirements of the Artificial Pancreas. Ann. Biomed. Eng. 44, 3158–3172 (2016).

4. Bekiari, E. et al. Artificial pancreas treatment for outpatients with type 1 diabetes: systematic review and meta-analysis. BMJ 361, k1310 (2018).

5. Diabetes.co.uk. Artificial Pancreas https://www.diabetes.co.uk/artificial-pancreas.html (2019)

6. Ramli, R., Reddy, M. & Oliver, N. Artificial Pancreas: Current Progress and Future Outlook in the Treatment of Type 1 Diabetes. Drugs 79, 1089–1101 (2019).

7. Quintal, A., Messier, V., Rabasa-Lhoret, R. & Racine, E. A critical review and analysis of ethical issues associated with the artificial pancreas. Diabetes Metab. 45, 1–10 (2019).

8. Kumar, N., Joisher, H. & Ganguly, A. Polymeric Scaffolds for Pancreatic Tissue Engineering: A Review. Rev. Diabet. Stud. 14, 334–353 (2018).

9. Ravnic, D. J., Leberfinger, A. N. & Ozbolat, I. T. Bioprinting and Cellular Therapies for Type 1 Diabetes. Trends in Biotechnology vol. 35 1025–1034 (2017).

10. Akkouch, A., Yu, Y. & Ozbolat, I. T. Microfabrication of scaffold-free tissue strands for three-dimensional tissue engineering. Biofabrication 7, 031002 (2015).

11. Wojtasiński, Z. Polish researchers printed the world`s first bionic pancreas with vessels. PAP - Science in Poland (2019).

12. 3D bioprinted bionic pancreas to fight diabetes. https://www.3dnatives.com/en/bionic-pancreas-080420194/ (2019).


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