Harnessing Bioactive Ceramic for Organoid Engineering: Mechanisms, Applications, and Prospects in Regenerative Medicine

Abstract

Organoids are three-dimensional, stem-cell-derived tissue constructs that recapitulate the architecture and function of native organs, and they have rapidly emerged as transformative tools in regenerative medicine. Their translation from laboratory models to clinical therapies remains constrained, however, by the limitations of conventional culture matrices. Matrigel is the most widely used matrix. It suffers from batch-to-batch variability, an undefined composition, poor mechanical tunability, and a lack of instructive bioactivity. Bioactive ceramics offer a compelling alternative. Encompassing silicate-, phosphate-, and oxide-based formulations, these materials provide controllable ion-release profiles and structural versatility. They also possess a proven capacity to modulate cell behavior through biochemical and biophysical cues. This review systematically examines how the defining properties of bioactive ceramics intersect with the requirements of organoid formation, maturation, and transplantation. We focus on four key properties: ion release, surface bioactivity, mechanical support, and immunomodulation. We survey established and emerging combinations across bone, liver, intestine, biliary, and thyroid organoid systems. Fabrication strategies, including 3D-printed and sol–gel-derived ceramic scaffolds, are also discussed. Finally, we critically assess remaining challenges in vascularization, immune compatibility, and clinical scale-up, and we propose that the deliberate co-design of bioactive ceramics and organoid biology represents a paradigm shift in regenerative medicine. This approach offers a path toward functional, transplantable tissue constructs with genuine therapeutic potential.