Strategies for the Selection and Application of Biological Scaffolds in Organ-on-a-Chip Systems

As an emerging microphysiological system, organ-on-a-chip (OoC) replicates human organ structures and functions through microfabrication, holding promise as novel platforms for drug screening, disease modeling, and toxicity testing, although their broad application still faces significant validation challenges. This review systematically examines biomimetic scaffold selection strategies in OoC systems, with a focus on hydrogels, hydrogel microspheres, and other scaffold types. It details chip fabrication processes, including design concepts, material selection, microfabrication technology, and cell sources. By comparing physicochemical properties, biocompatibility, and functional characteristics of different materials, this paper explores optimal scaffold strategies for specific organ simulations. Based on comprehensive analysis, hydrogel scaffolds have become widely adopted for OoC construction due to their excellent biocompatibility and extracellular matrix-like properties. Synthetic polymers and bioceramic scaffolds demonstrate significant value in meeting specific mechanical requirements and constructing complex microstructures. As a novel hydrogel form, hydrogel microspheres exhibit considerable potential in dynamic culture simulation and drug delivery owing to their high specific surface area and controllable release capabilities. This paper also discusses future directions, including personalized scaffold design, intelligent responsive materials, and multiorgan coupling systems, providing theoretical guidance for advancing OoC technology.