title: Controlling the 3D architecture of Self-Lifting Auto-generated Tissue Equivalents (SLATEs) for optimized corneal graft composition and stability.
abstract: Ideally, biomaterials designed to play specific physical and physiological roles in vivo should 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.
authors.affiliation: Institute of Genetic Medicine, Newcastle University, International Centre for Life, Newcastle-upon-Tyne, UK.
authors.forename: Ricardo M
authors.initials: RM
authors.lastname: Gouveia
authors.affiliation: Tissue Engineering Group, Department of Histology, Faculty of Medicine and Dentistry, University of Granada, Granada, Spain.
authors.forename: Elena
authors.initials: E
authors.lastname: González-Andrades
authors.affiliation: Laboratory of Biomaterials and Optics, Optics Department, Faculty of Sciences, University of Granada, Granada, Spain.
authors.forename: Juan C
authors.initials: JC
authors.lastname: Cardona
authors.affiliation: San Cecilio University Hospital, Ophthalmology Service, Granada, Spain.
authors.forename: Carmen
authors.initials: C
authors.lastname: González-Gallardo
authors.affiliation: Laboratory of Biomaterials and Optics, Optics Department, Faculty of Sciences, University of Granada, Granada, Spain.
authors.forename: Ana M
authors.initials: AM
authors.lastname: Ionescu
authors.affiliation: Tissue Engineering Group, Department of Histology, Faculty of Medicine and Dentistry, University of Granada, Granada, Spain.
authors.forename: Ingrid
authors.initials: I
authors.lastname: Garzon
authors.affiliation: Tissue Engineering Group, Department of Histology, Faculty of Medicine and Dentistry, University of Granada, Granada, Spain.
authors.forename: Miguel
authors.initials: M
authors.lastname: Alaminos
authors.affiliation: Schepens Eye Research Institute and Massachusetts Eye and Ear, Department of Ophthalmology, Harvard Medical School, Boston, MA, USA. Electronic address: miguel_gonzalez@meei.harvard.edu.
authors.forename: Miguel
authors.initials: M
authors.lastname: González-Andrades
authors.affiliation: Institute of Genetic Medicine, Newcastle University, International Centre for Life, Newcastle-upon-Tyne, UK. Electronic address: che.connon@newcastle.ac.uk.
authors.forename: Che J
authors.initials: CJ
authors.lastname: Connon
mesh_terms: D040761:Biomimetic Materials / Q000737:chemistry*; D002478:Cells, Cultured; D003315:Cornea / Q000166:cytology* / Q000254:growth & development*; D003319:Corneal Stroma / Q000166:cytology* / Q000503:physiopathology*; D016039:Corneal Transplantation / Q000379:methods*; D019573:Epithelium, Corneal / Q000166:cytology; D006801:Humans; D066330:Printing, Three-Dimensional; D023822:Tissue Engineering / Q000379:methods*
keywords: Corneal stroma; SLATEs; Tissue templating