Controlling the 3D architecture of Self-Lifting Auto-generated Tissue Equivalents (SLATEs) for optimized corneal graft composition and stability
Authors
Ricardo M. Gouveia, Elena Gonzalez-Andrades, Juan C. Cardona, Carmen Gonzalez-Gallardo, Ana M. Ionescu, Ingrid Garzon, Miguel Alaminos, Miguel Gonzalez-Andrades, Che J. Connon
Institution
Newcastle University
Country
United Kingdom
Year
2017
Journal
Biomaterials
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 biofabrication
of easy-retrievable, scaffold-free human tissues with controlled structural, compositional, and
functional properties to replace corneal, as well as other, tissues.