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4D Corneal Tissue Engineering: Achieving Time-Dependent Tissue Self-Curvature through Localized Control of Cell Actuators

Lookup NU author(s): Martina Miotto, Dr Ricardo Martins GouveiaORCiD, Professor Francisco Figueiredo, Professor Che ConnonORCiD



This is the authors' accepted manuscript of an article that has been published in its final definitive form by WileyWiley - V C H Verlag GmbH & Co. KGaA, 2019.

For re-use rights please refer to the publisher's terms and conditions.


While tissue engineering is widely used to construct complex tridimensional biocompatible structures, researchers are now attempting to extend the technique into the fourth dimension. Such fourth dimension consists in the transformation of 3D materials over time, namely by changing their shape, composition, and/or function when subjected to specific external stimuli. In this study, we instead explored producing a 4D biomaterial with an internal mechanism of stimulus, using contractile cells as bio-actuators to change tissue shape and structure. Specifically, we aimed at producing cornea-shaped, curved stromal tissue equivalents via the controlled, cell-driven curving of collagen-based hydrogels. This was achieved by modulating the activity of the bio-actuators in delimited regions of the gels using a contraction-inhibiting peptide amphiphile. The self-curved constructs were then characterized in terms cell and collagen fibril re-organization, gel stiffness, cell phenotype, and the ability to sustain the growth of a corneal epithelium in vitro. Overall, our results showed that the structural and mechanical properties of self-curved gels acquired through a 4D engineering method were more similar to those of the native tissue, and represented a significant improvement over planar 3D scaffolds. In this perspective, this study demonstrates the great potential of cell bio-actuators for 4D tissue engineering applications.

Publication metadata

Author(s): Miotto M, Gouveia RM, Ionescu AM, Figueiredo F, Hamley IW, Connon CJ

Publication type: Article

Publication status: Published

Journal: Advanced Functional Materials

Year: 2019

Volume: 29

Issue: 8

Print publication date: 21/02/2019

Online publication date: 11/01/2019

Acceptance date: 14/12/2018

Date deposited: 08/01/2019

ISSN (print): 1616-301X

ISSN (electronic): 1616-3028

Publisher: WileyWiley - V C H Verlag GmbH & Co. KGaA


DOI: 10.1002/adfm.201807334

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Funder referenceFunder name
BB/N021576/1Biotechnology and Biological Sciences Research Council (BBSRC)