# Customizable Hydrogel Coating of ECM-Based Microtissues for Improved Cell Retention and Tissue Integrity

## TL;DR

Researchers developed a customizable hydrogel coating for microtissues to improve cell retention and tissue stability in tissue engineering.

## Contribution

A novel, tunable hydrogel coating method using calcium carbonate and alginate to enhance microtissue integrity and cell retention.

## Key findings

- Calcium carbonate nanoparticles in microtissues can form a protective hydrogel coating when exposed to alginate.
- The hydrogel coating prevents cell loss and protects microtissues from degradation in vitro and in vivo.
- Coating thickness can be precisely controlled by adjusting fabrication parameters.

## Abstract

Overcoming the oxygen diffusion limit of approximately 200 µm remains one of the most significant and intractable challenges to be overcome in tissue engineering. The fabrication of hydrogel microtissues and their assembly into larger structures may provide a solution, though these constructs are not without their own drawbacks; namely, these hydrogels are rapidly degraded in vivo, and cells delivered via microtissues are quickly expelled from the area of action. Here, we report the development of an easily customized protocol for creating a protective, biocompatible hydrogel barrier around microtissues. We show that calcium carbonate nanoparticles embedded within an ECM-based microtissue diffuse outwards and, when then exposed to a solution of alginate, can be used to generate a coated layer around the tissue. We further show that this technique can be fine-tuned by adjusting numerous parameters, granting us full control over the thickness of the hydrogel coating layer. The microtissues’ protective hydrogel functioned as hypothesized in both in vitro and in vivo testing by preventing the cells inside the tissue from escaping and protecting the microdroplets against external degradation. This technology may provide microtissues with customized properties for use as sources of regenerative therapies.