Development of porous silicon as a scaffold for the delivery of cells into ocular tissue

Author: Suet Peng Low

Low, Suet Peng, 2008 Development of porous silicon as a scaffold for the delivery of cells into ocular tissue, Flinders University, School of Chemical and Physical Sciences

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Porous silicon has been shown to support the growth of cells and its capacity to fully degrade into harmless silicic acid, two properties that make porous silicon an appealing biomaterial. In this thesis, porous silicon was first tested in its suitability to support the growth of two different cell lines in vitro. The porous silicon surface was also surface-modified by oxidation, silanisation and by protein coatings to enhance its attachment properties. We found that silanisation with 3-aminopropyltrimethoxysilane (APTMS) was the simplest surface modification method that yielded the best cellular attachment characteristics and cellular morphology in comparison to the other surface modification methods tested. It was also discovered that surface modification was necessary to control the degradation rate of the porous silicon surface. APTMS-modified surfaces and thermally oxidised surfaces were both able to slow the degradation rate of the porous silicon surface and were thus used for subsequent experimentation. Different forms of porous silicon were also tested, including membranes and particles. It was also discovered that certain colorimetric cell viability assays have the ability to interact with the redox-active porous silicon surface, thus yielding false positives. We focused upon assays such as Alamar Blue and the dye neutral red, both of which were able to generate a positive result with the porous silicon surface in the absence of cells. We have shown that the porous silicon membranes were capable of supporting immortalised cells as well as primary cells isolated from human tissue. The biocompatibility of the porous silicon membranes was tested in a rat eye model, where the tissue response to the membrane could be observed macroscopically. It was noticed that there was a small inflammatory response around the membranes. Vascularisation and noticeable swelling was isolated to monofilament nylon sutures rather than the implanted membranes. The biocompatibility of porous silicon in the eye was also investigated through histological methods. The implanted porous silicon membranes only induced a small foreign body response which was noticeably smaller than the inflammatory response observed around commonly-used monofilament nylon sutures. This is the first time that histological and microscopy evidence is given to show that porous silicon has good tissue biocompatibility. We offer evidence that the porous silicon membranes are able to degrade whilst implanted and the evidence also suggests that they are able to undergo full degradation. Porous silicon was also investigated for its ability to act as a support scaffold for the delivery of cells into tissue. Primary cells were successfully cultured and implanted into eye of an animal. After one week, cells could be observed migrating away from the membrane into the surrounding tissue. Therefore an enhanced porous silicon-based support has been developed that supports the attachment and growth of mammalian cells. This support is also biocompatible, biodegradable and can be used to deliver cells into tissue.

Keywords: Porous silicon,limbus,ophthalmology,biomaterials

Subject: Chemistry thesis

Thesis type: Doctor of Philosophy
Completed: 2008
School: School of Chemical and Physical Sciences
Supervisor: Professor Nicolas Voelcker