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.
Highlights
The development of a corneal stroma equivalent requires theR.M
Cells grown on isotropic peptide amphiphile (PA) templates were expected to deposit ECM materials depending on their arbitrary position, and form randomlyorganized (R-) Self-Lifting Analogous Tissue Equivalents (SLATEs)
Tissues generated on the alignment-inducing, anisotropic template were comprised by highly-ordered cells and tissue (Fig. 1a) and were less friable during manipulation than those produced on PA-coated glass
Summary
The development of a corneal stroma equivalent requires theR.M. Gouveia et al / Biomaterials 121 (2017) 205e219 effective crosslinking, can provide a long-term stable corneal replacement. Recent advances within the field of Materials Science have led to the development of dynamic surface templates that instruct cells to fabricate tissues using a bottom-up approach, and subsequently respond to that tissue (e.g., by degrading, gaining/changing bio-activity) [10] These materials are capable of directing cells to bio-fabricate tissues, which can subsequently detach by virtue of a change in the material's characteristics, typically in response to external physical (temperature, magnetic field), chemical (ionic strength, pH), or biological (anabolic or catabolic) stimuli (reviewed in [11,12]). These biofabricates contain no artificial or exogenous biomaterials, synthetic scaffolds, or carriers
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