Dissecting in vitro models for toxicology

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The use of tissue engineered tissues and organs as in vitro alternatives to animal testing is gaining importance, especially in the context of the ban on animal testing for consumer products currently in place in Europe (EU Directive 76/768/EEC) which is expected to expand worldwide. To standardize in vitro models for testing, care must be taken to assure that each "alternative" not only mimics the tissue architecture as the target, but also shares key biochemical, morphological, physiological, and even genetic components. Tissue engineering methods utilize a wide range of synthetic polymers to natural biomaterials (with or without additional bioactive co-factors) as scaffolding to create appropriate 3-dimensional environments upon which cells can attach to proliferate and differentiate into physiologically functional tissues that are structurally similar to the native tissue. The understanding of how "tissue forms and architecture" (scaffolds) regulates tissue development and function, however, is somewhat lacking, making comparison amongst models daunting, as different groups will report different safety and efficacy results based on the model they have selected. Our objective is to dissect out the developmental mechanisms involved in engineering tissues, specifically the role of biomaterials as scaffolding used in reconstructing whole tissues. We focus on the cornea as a test bed since ocular irritancy testing is widely used in industry for safety testing of compounds for personal use and household consumer products. Very briefly, to keep things manageable, we focus only the biomaterials that are commonly used as scaffolding in in vitro corneal tissue engineering to answer the following questions: What is the best type of material for scaffolds - an inert, degradable synthetic polyester, an inert plant-based fibre or biointeractive protein? Or, does the scaffold matter at all, or it is all in optimization of the mechanical properties or topology of the scaffolding? Once we have identified the fundamental desired characteristics of the basic scaffold, we will use this knowledge to develop 1) an in vitro disease model for drug efficacy testing; and 2) a fully synthetic analog of a corneal model for safety/ toxicology testing.