ABSTRACT

The increasing rate of cancer patients worldwide, and especially Africa has led to numerous efforts to battle it. One approach to this has been localized drug delivery to reduce the quantity of drugs needed for therapeutic effect. Poly-di-methyl-siloxane (PDMS) is an elastomer with much focus on it as a microfluidic device. PDMS is one polymer of choice for localized drug delivery due to its biocompatibility, transparency, and ease of fabrication. However, its highly hydrophobic nature does not allow it to be used without modification. This work presents results of experimental and computational methods for PDMS surface modification. Also computational results of shear assay model for the effects on surface modification on cell adhesion is present. Modifying the surface of the PDMS was done by varying the mix ratio and curing temperatures after fabrication. The results from the experiment shows that low base to curing agent ratio and increasing curing temperature gives a highly stiff PDMS. Also, the PDMS treatment via boiling water and Ultraviolet Ozone (UVO) methods makes it hydrophilic with the generation of hydroxyl (OH) group on the substrates. These studies provided understanding of cell-surface interaction on a multi-scale. Morphological studies with Scanning Electron Microscope (SEM) reveal a layer and textured featured formed on UVO treated and PLGA coated PDMS. Shear assay model showed that cells on modified PDMS surface low energy release rate on application of shear load. This signifies that cells adhered to the modified surfaces better, thus could not be easily detached.

1.0 CHAPTER ONE

1.1 INTRODUCTION

The treatment of injury, disease and congenital malformation from traditional to scientific has been part of the human experience. Better ways are sought to improve human life. One disease that is currently taking human lives is cancer. Cancer is second only to cardiovascular disease [1, 2], and with current trends is likely to become the leading cause of death globally by 2030 [1].

In a quest to battle this globally threatening disease, research is being done to improve on conventional methods of detection and treatment [3-6]. This is to reduce the various side effects that accompany existing methods based on surgical procedures, radiation therapy, including bulk systemic chemotherapy. It is important to explore alternative approaches that can reduce the killing of normal or healthy cells during the cancer treatments.

An emerging field, tissue engineering, which provides an approach for the repair and fabrication of tissue from living cells [7] offers a better approach to cancer treatment. Soft tissue engineering plays a vital role in the treatment of cancer through implantable device. Implantable cancer treatment device enables localized drug delivery [6, 8]. This reduces the quantity of drug that is needed to have therapeutic effect significantly. Thus potential side effects of localized cancer drug delivery become much less than bulk systemic chemotherapy.

In localized cancer drug delivery, one polymer which has been used as a packaging material for controlled drug release is poly-di-methyl-siloxane (PDMS) [9]. PDMS is a biocompatible polymer, according to the United States Food and Drug Administration (US FD) and after some toxicity studies [10, 11], it has been approved for applications in implantable biomedical devices in humans [12, 13]. The challenge, however, lies in the physiochemical properties of PDMS surfaces, which may affect proper cell function, leading to poor integration of biomedical implants.

Even though some general correlations between the physiochemical properties of a given surface and its performance as a support for cell adhesion and growth have been established, there is limited understanding of the multi-scale interactions that lead to cell adhesion. There is therefore the need to study the effects of cell adhesions at multiple scales (nano, micro and meso).

1.1.2 Objectives

There are still significant unresolved issues that must be resolved to enable the design of improved adhesion between cells and implantable drug delivery device [15, 16]. These must be resolved to ensure improved integration between PDMS and biological cells/tissue. This will be done by the fabrication of PDMS and the engineering PDMS surfaces to make them more suitable for applications in an implantable cancer treatment device. This will be achieved by the use of surface modification and extra-cellular matrix (ECM) coating techniques.