Bioengineering Pancreatic Organoids and iPSC-Derived β-Cells for Diabetes: Materials, Devices, and Translational Challenges

Abstract

Diabetes mellitus is primarily caused by the loss or malfunction of insulin-producing beta-cells, and although current therapies improve glycemic control, they do not restore physiologic insulin secretion. Advances in stem cell biology and organoid engineering have led to the development of pancreatic organoids and induced pluripotent stem cell (iPSC)-derived beta-cells as promising platforms for disease modeling, drug testing, and regenerative medicine. Pancreatic organoids generated from ductal, acinar, or progenitor populations can recapitulate key anatomical and functional features of native pancreatic tissue, enabling studies of development, injury, and regeneration. In parallel, improvements in iPSC differentiation protocols have produced beta-like cells capable of insulin secretion in response to glucose, although achieving full functional maturity remains a challenge. Bioengineering strategies, including biomaterial scaffolds, microfluidic platforms, endothelial co-culture systems, three-dimensional bioprinting, and CRISPR-based genome editing, have enhanced the stability, vascular compatibility, and functional performance of both organoid and iPSC-derived systems. Despite these advances, variability in differentiation efficiency, limited beta-cell maturity, and poor long-term survival continue to hinder clinical translation. Together, pancreatic organoids and iPSC-derived beta-cells represent complementary platforms that advance fundamental research and support the development of beta-cell replacement therapies, with ongoing integration of bioengineering approaches expected to accelerate progress toward reproducible, scalable, and clinically relevant beta-cell regeneration.