Integrating Spheroids with Cell-Instructive Biomaterials in

Tissue Engineering

Heungsoo Shin, Ph.D.

Dept. of Bioengineering, Hanyang University, Seoul, Republic of Korea

hshin@hanyang.ac.kr

The growing interest in engineering three-dimensional (3D) tissues continues to drive significant advances in tissue engineering and regenerative medicine. Among various approaches, the use of micro-scale functional units—such as cell aggregates, sheets, or spheroids—has emerged as a promising strategy to recapitulate heterogeneous, complex cellular microenvironment of native target tissues. Stem cell spheroids and organoids have been extensively explored as modular building blocks, as directly assembled or integrated into biomimetic matrices. Effectively harnessing spheroids for constructing 3D tissues requires overcoming several key technological challenges including rapid and size-controlled spheroid production, modulation of spheroid functionality and modularity, precise spatial localization and organization of spheroids within defined biodegradable scaffolds, and promotion of vascularized structures to sustain long-term cell viability and metabolic activity. Integrating cell-instructive biomaterials with spheroid systems may provide an effective strategy to address these challenges by offering a supportive and dynamic microenvironment that guides cellular behaviors and tissue morphogenesis. This presentation highlights our research efforts combining cell-instructive biomaterials with multicellular spheroids to engineer 3D constructs for tissue regeneration, with a particular emphasis on musculoskeletal tissue applications.