Hydrogel Microspheres Empowering Organ-on-a-Chip Systems: Innovations and Applications

Organ-on-a-chip (OoC) is an in vitro platform that uses microfluidic technology to simulate the microphysiological environment of human organs. It can reconstruct tissue architecture, mechanical microenvironments, and biochemical signaling. Since its inception, OoC technology has evolved from 2D static cultures to 3D dynamic biomimetic models. It is widely used in physiological and disease modeling, drug development and screening, and personalized medicine. In recent years, with the rapid progress in materials science and manufacturing technologies, hydrogel microspheres (HMs) with excellent biocompatibility and tunable properties have become a focus in biomedical research. HMs can mimic the properties of the extracellular matrix (ECM) and address the problem of lacking biochemical and biophysical signals in traditional OoC systems. This has greatly promoted the development of OoC technology and given it new abilities, such as accurately simulating cellular niche microenvironments, building complex system models and 3D tissue networks, encapsulating and delivering target cells or therapeutic agents, and studying intercellular and inter-organ crosstalk. This review introduces the concept, characteristics, and fabrication strategies of OoC systems, discusses the materials and methods for HM fabrication and integration, explores recent applications of HMs in OoC platforms, and offers insights into the development of "smart" HMs for advanced OoC systems.