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.