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Controlling the 3D architecture of Self-Lifting Auto-generated Tissue Equivalents (SLATEs) for optimized corneal graft composition and stability

Lookup NU author(s): Dr Ricardo Martins GouveiaORCiD, Professor Che ConnonORCiD



This work is licensed under a Creative Commons Attribution 4.0 International License (CC BY 4.0).


Ideally, biomaterials designed to play specific physical and physiological roles in vivoshould comprise components and microarchitectures analogous to those of the native tissues they intend to replace. For that, implantable biomaterials need to be carefully designed to have the correct structural and compositional properties, which consequently impart their bio-function. In this study, we showed that the control of such properties can be defined from the bottom-up, using smart surface templates to modulate the structure, composition, and bio-mechanics of human transplantable tissues. Using multi-functional peptide amphiphile-coated surfaces with different anisotropies, we were able to control the phenotype of corneal stromal cells and instruct them to fabricate self-lifting tissues that closely emulated the native stromal lamellae of the human cornea. The type and arrangement of the extracellular matrix comprising these corneal stromal Self-Lifting Analogous Tissue Equivalents (SLATEs) were then evaluated in detail, and was shown to correlate with tissue function. Specifically, SLATEs comprising aligned collagen fibrils were shown to be significantly thicker, denser, and more resistant to proteolytic degradation compared to SLATEs formed with randomly-oriented constituents. In addition, SLATEs were highly transparent while providing increased absorption to near-UV radiation. Importantly, corneal stromal SLATEs were capable of constituting tissues with a higher-order complexity, either by creating thicker tissues through stacking or by serving as substrate to support a fully-differentiated, stratified corneal epithelium. SLATEs were also deemed safe as implants in a rabbit corneal model, being capable of integrating with the surrounding host tissue without provoking inflammation, neo-vascularization, or any other signs of rejection after a 9-months follow-up. This work thus paves the way for the de novo bio-fabrication of easy-retrievable, scaffold-free human tissues with controlled structural, compositional, and functional properties to replace corneal, as well as other, tissues.

Publication metadata

Author(s): Gouveia RM, González-Andrades E, Cardona JC, González-Gallardo C, Ionescu AM, Garzon I, Alaminos M, González-Andrades M, Connon CJ

Publication type: Article

Publication status: Published

Journal: Biomaterials

Year: 2017

Volume: 121

Pages: 205-219

Print publication date: 01/03/2017

Online publication date: 23/12/2016

Acceptance date: 21/12/2016

Date deposited: 01/03/2017

ISSN (print): 0142-9612

ISSN (electronic): 1878-5905

Publisher: Elsevier


DOI: 10.1016/j.biomaterials.2016.12.023


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Funder referenceFunder name
FEDER funds, European Union
BB/I008187/1Biotechnology and Biological Sciences Research Council
FIS PI14/0955Spanish Plan Nacional de Investigation Cientifica, Desarrollo e Innovacion Tecnologica (I + D + I) from the Spanish Ministry of Economy and Competitiveness (Instituto de Salud Carlos III)
MR/K017217/1Medical Research Council
FIS PI14/0955