Advanced engineering strategies in human organoids for tissue repair and regeneration

Abstract

Abstract Tissue damage and functional disorders due to diseases or trauma can lead to irreversible organ failure. Conventional treatment strategies such as organ transplantation or stem cell therapy are often limited by immune rejection, donor shortages and poor regenerative effects. Organoids, 3D miniature tissues derived from stem cells, can provide a promising approach for tissue repair and regeneration by recapitulating the complex structure and functional properties of native organs with high plasticity, scalability and physiological relevance. In this review, we present novel engineering approaches to human organoids such as generation, optimization and translational applications for tissue repair. We then introduce core technologies including organoid-on-chip, hydrogels and 3D bioprinting, which collectively address the challenges such as tissue immaturity, inadequate vascularization and poor host integration. We also discuss applications of engineered organoids to repair multiple tissues (e.g. heart, lung, brain, bone and skin) and summarize recent advances in preclinical models and their potential clinical translational applications. Finally, we discuss key challenges for organoid-based therapy including functional maturation, integration with vascular, neural, and immune systems, complexity of reproducing native biomechanical environments, ethical concerns, as well as possible solutions and directions for their application in regenerative medicine.