Microscale strategies in engineering the pancreas: Toward clinical translation

Microscale engineering technologies are reshaping strategies for pancreatic islet replacement therapies. This review surveys three broad domains where microscale approaches are demonstrating considerable promise. In biomanufacturing applications, microscale platforms enhance control over oxygenation, nutrient delivery, hydrodynamic forces, and aggregate size, addressing longstanding challenges in the scalable and consistent production of stem cell-derived islets. In preclinical processing of therapeutic replacement and augmentation devices, we review recent advances in micro- and macroencapsulation, with emphasis on how microscale material design, membrane architecture, and oxygen-management strategies collectively aim to balance immunoprotection with adequate mass transport, an essential requirement for long-term graft survival. Finally, we also examine the expanding toolkit for functional assessment across the implantation lifecycle. Integrated microsensors and microfluidic testing systems enable localized, real-time monitoring of metabolic behavior before and during implantation, while transport-defined ex vivo platforms improve failure-mode analysis after graft retrieval. Together, these categories provide a coherent framework illustrating how microscale systems are being leveraged to improve the robustness, interpretability, and translational readiness of next-generation islet replacement therapies.