Master of Philosophy
Intelligent Polymer Research Institute
Visual impairment due to corneal disease is a global health concern with few FDA-approved pharmaceuticals being developed. In the cornea, the interactions between the various cell types present are essential for its functioning. In particular, innervation through sensory nerves is crucial for optimal functioning of this tissue. However, the mechanisms underlying these interactions are poorly understood, and representative 3D innervated in vitro cornea models could be used as systems to model the native situation. Therefore, an innervated model of the cornea is proposed and initiated. Electrocompacted collagen constructs serve as a basis for mimicking the cornea, and its mechanical, optical, and degradative properties are shown to be favorable. Furthermore, three dimensional extrusion- based printing has been employed to print methacrylated gelatin, and this scaffold was shown to support neuronal cell survival (83.4% viability 1 day after printing). A sustained release of neural growth factor to induce differentiation was established through incorporation of growth- factor loaded microparticles within the electrocompacted collagen. Additionally, the bioactivity was confirmed through an in vitro PC12 cell assay. The two biomaterials have been interfaced to fabricate a model to guide neuronal innervation. The current model shows potential in mimicking the complex structure of the cornea, but some optimization is required for neurite outgrowth. In the future, a viable in vitro corneal model could be used to provide fundamental insight into the process of corneal innervation and corneal diseases, as well as pre-clinical toxicity testing of new ocular drugs.
van Tienderen, Gilles Sebastiaan, Towards an in vitro innervated model of the cornea, Master of Philosophy thesis, Intelligent Polymer Research Institute, University of Wollongong, 2018. https://ro.uow.edu.au/theses1/1025
Unless otherwise indicated, the views expressed in this thesis are those of the author and do not necessarily represent the views of the University of Wollongong.