Hydrogel-based preparation of cell aggregates for biomedical applications

Cell aggregates are widely used either as in-vitro models for drug screening, fundamental studies on disease progression and developmental biology, as well as in-vivo injectable cells for tissue regeneration. Compared to single-cell suspensions, cell aggregates retain superior cell viability, mimic in-vivo microenvironments and enhance functional properties, such as superior anti-inflammatory properties of mesenchymal stem/stromal cell aggregates or enhanced albumin production by hepatocyte aggregates. Cell aggregates can be either prepared by conventional spontaneous aggregation, or advanced substrate-based and technology-assisted methods, which have been well described in previous reviews. However, hydrogel-based preparation of cell aggregates is a novel, hitherto rarely considered method compared to conventional preparation of cell aggregates, such as hanging drops and commercial AggreWell^TM plates. This review will mainly focus on two-dimensional (2D) hydrogel surface -based and three-dimensional (3D) hydrogel embedding-based preparation of cell aggregates by revealing the underlying mechanisms and highlighting some of their potential biomedical applications.