3D bioprinted connections in Liver‒Pancreas crosstalk: Lessons learned and future directions

The complexity of metabolic crosstalk between the liver and pancreas, which controls glucose and homeostasis levels, has been intriguing for models based on conventional in vitro systems. However, the 3D bioprinting path has created an incredible platform of multicellular and spatially concerted microtissues that mimic the interaction of the pancreas. This discovery contributes important insights into metabolic organization, regenerative strategies, and disease mechanisms. Therefore, our review delves into recent advancements in 3D bioprinted crosstalk between liver and pancreas constructs, with focus on biomaterial scaffolds, engineered microenvironments, and how dynamic perfusion systems imitate signaling between hepatocytes, stromal components, and pancreatic β-cells. The relevance of nutrient flow, coculture geometry, and bioink composition to improve insulin responsiveness, lipid metabolic processes, and glucose uptake has taken the focal point, while the integration of microfluidic bioreactors and biosensing scaffolds provides real-time metabolic monitoring and testing of drugs. Persistent threats still exist in preserving tissue viability, functional connectivity, and vascularization. Future research could delve into creation of vascularized multiorgan chips and evaluate therapies, stem cell-based cell lines, and AI-backed bioprinting for customized disease modeling. Integrating bioengineering and endocrine biology in 3D bioprinting of the liver‒pancreas system could improve scientific knowledge of interorgan crosstalk in metabolic disorders.