# Reprogrammable 4D tissue engineering hydrogel scaffold via reversible ion printing

## TL;DR

A new hydrogel scaffold can change shape in a controlled way and be reprogrammed, which could help in tissue engineering.

## Contribution

A reprogrammable hydrogel system using ion-transfer printing for 4D tissue engineering is introduced.

## Key findings

- Hydrogels with tunable crosslinking gradients enable programmable shape deformation.
- Shape morphing can be reprogrammed using a secondary ion-transfer printing process.
- The system supports long-term cell differentiation in tissue-like constructs.

## Abstract

Shape-morphable hydrogel scaffolds recapitulating morphological dynamism of native tissues represent an elegant tool for tissue engineering (TE) applications. Current morphable hydrogels are predominantly based on multimaterial structures, which involve complicated and time-consuming fabrication protocols, and are often limited to unidirectional deformation. This work reports on the development of a transformable hydrogel system using a fast, simple, and robust fabrication approach for manipulating the shapes of soft tissues at defined maturation states. Simply by using an ion-transfer printing (ITP) technology, a tunable ion crosslinking density gradient across the hydrogel thickness has been incorporated, which enables preprogrammable deformations upon further swelling in cell culture media. Combining with a surface patterning technology, cell-laden constructs (bioconstructs) capable of morphing in multiple directions are deformed into sophisticated configurations. Not only can the deformed bioconstructs recover their original shapes by chemical treatment, but at user-defined times they can also be incorporated with new, different spatially controlled gradient crosslinking via the ITP process, conferring 3D bioconstruct shape reprogrammability. In this manner, unique “3D-to-3D” shape conversions have been realized. Finally, effective shape manipulation in engineered cartilage-like tissue constructs has been demonstrated. These morphable scaffolds may advance 4D TE by enabling sophisticated spatiotemporal control over construct shape evolution.

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•A novel ITP strategy was developed to generate crosslinking gradients within hydrogels.•The resulting hydrogels exhibited programmable shape-morphing capabilities.•Shape morphing could be reprogrammed via a secondary ITP process.•The hydrogels supported long-term cell differentiation for tissue regeneration.•Tissue constructs could be both programmed and reprogrammed using the ITP approach.

A novel ITP strategy was developed to generate crosslinking gradients within hydrogels.

The resulting hydrogels exhibited programmable shape-morphing capabilities.

Shape morphing could be reprogrammed via a secondary ITP process.

The hydrogels supported long-term cell differentiation for tissue regeneration.

Tissue constructs could be both programmed and reprogrammed using the ITP approach.