Bioprosthetic cornea: using polymeric templates for directed stem cell growth

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The cornea is our window to the world, once compromised by wounding, disease or age, a loss of vision results. By improving our understanding of corneal structure and providing new methods of corneal transplantation the sight of many more patients can be restored. Currently, corneal transplantation requires a continuous supply of healthy donor corneas. However worldwide demand has grown and taken together with an aging population and the rapid rise in laser eye surgery (which can negatively affect the donor tissue suitability for transplantation) the search for an effective engineered replacement is essential if current levels of corneal transplantation are to be maintained. This investigation stems from our previous work in understanding the molecular structure underpinning corneal transparency, the development of novel corneal biomaterials and the limitations of the current corneal stem cell transplantation techniques, specifically the materials used to grow and convey the stem cells to the patient. Previously, we have quantified the nanostructure of the cornea and related this structure to the preservation of corneal transparency; furthermore we have applied these measurements to the design of new corneal biomaterials capable of supporting corneal epithelial stem cell differentiation and growth. Therefore, we will draw on our knowledge of corneal structure, corneal stem cell isolation and cultivation and novel biomaterials to engineer a tissue suitable for corneal transplantation. To do this we will develop a template made from tractable regularly spaced aligned polymers (reflecting the natural state of corneal nanostructure). The template will contain protein fragments recognisable by the human corneal stem cells enabling them to attach in a highly ordered and controlled manner. Once attached the cells will be chemically induced to differentiate and produce collagen fibres. The alignment of these fibres will be guided by the cells orientation. The template will then slowly lose its integrity and detach from the cells by way of enzymes released by the corneal cells, thus releasing the aligned collagen as a tissue engineered collagen mat. These mats will then be stacked and compressed to produce a robust biomaterial made solely from human proteins (mostly collagen), the polymer template having been removed during processing. The biomaterials mechanical strength and ability to support corneal epithelial growth upon its surface will then be tested. We have already shown that compressed mats of rat tail collagen are both mechanically robust as well as excellent substrates for corneal epithelial cell growth. This work represents a significant step forward in the development of biomaterials. Instead of designing and using bio-compatible polymers to represent tissue for transplantation our approach is to use the polymers merely as a template allowing the cells to produce the actual biomaterial. Furthermore, since the template is easily discarded the cell based biomaterial represents the ultimate in biocompatibility as it is comprised of human proteins possibly even derived from cells taken from the patient's own body. The beneficiaries of this work would be those working in the fields of polymer chemistry as the development of aligned polymers containing protein fragments that are both recognised and degraded by cells is not trivial. Scientists in the blossoming field of biomaterials would be given a new direction in the development of truly bio-compatible materials (i.e. ones derived from stem cells). Tissue engineers would be given a new tool with which they could create similar stem cell based materials for bone, skin etc. repair and finally ocular regenerative medicine would benefit from the development of a replacement human donor corneal tissue.