# Rapid Generation of Fusable Cell Beads for Multi‐Scale Human Living Materials Assembly

## TL;DR

A new method creates living cell beads that can be used for tissue engineering and disease modeling, offering better control and faster production than traditional spheroids.

## Contribution

A novel method combining glycoengineering, click chemistry, and superhydrophobic surfaces to rapidly produce living beads with controlled size and improved viability.

## Key findings

- Living beads are rapidly produced with enhanced cell viability and spreading over 14 days.
- Living beads maintain spheroid characteristics like fusion into multi-scale structures and cellular migration.
- The method allows controlled bead size independent of cell density, overcoming a key limitation of traditional spheroids.

## Abstract

Three‐dimensional self‐assembled cellular aggregates, such as spheroids, provide unique building blocks for bottom‐up tissue engineering and in vitro disease modeling. Nevertheless, traditional spheroid production methods require prolonged cell aggregation times and are highly dependent on cell type, requiring frequent optimization steps. Additionally, spheroids’ size is dependent on their cell density, preventing a control over their final volume. Herein, a methodology combining metabolic glycoengineering and click chemistry with superhydrophobic surfaces is described to rapidly create spherically structured living bead units, that can surpass the fabrication constraints of conventional spheroids. Compared to spheroids produced in low attachment settings, the living beads comprising various cell types (i.e., stem, endothelial, and cancer cells) are rapidly produced and demonstrate enhanced cell viability and cell spreading over 14 days, while maintaining principal spheroid characteristics, namely the fusion into multi‐scale living materials and cellular migration capabilities. In addition, this methodology enables the production of living beads with controlled size, independently of cell density, overcoming a key limitation of current spheroid production methods. The enhanced reproducibility, reduced cell assembly time, and improved handling make these spherically structured living beads a valuable alternative, with broad application in bottom‐up tissue engineering approaches and disease modeling applications.

Living beads are produced through the combination of metabolic glycoengineering, click chemistry, and superhydrophobic surfaces, to develop a spheroid alternative for bottom‐up tissue engineering and disease modeling. The living beads present a size independent of cell density and a rapid fabrication methodology, providing a platform that can fuse into multi‐scale structures or be integrated into other tissue‐mimetic platforms.