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Surface Modification Of Polymeric Biomaterials For Cell/Tissue Integration

Surface Modification Of Polymeric Biomaterials For Cell/Tissue Integration

ABSTRACT

This thesis presented the surface modification of Polydimethyl Siloxane (PDMS) to enhance surface wettability and surface roughness. Physical and chemical modifications were performed on cured surfaces of PDMS and PDMS-based nano-composites. Firstly, physical modifications were done by direct coating of PDMS-based substrates with biopolymers such as polyethylene glycol (PEG), poly lactic-co-glycolic acid (PLGA) and sodium alginate (SA).

On the other hand, coatings were done with the biopolymers (PEG, PLGA, and SA) on pre-stretched PDMS-based substrates. Coated and uncoated, as well as treated surfaces of PDMS and PDMS-based nano-composites, were characterized by auroscope optical microscope.

Substrates wettability were characterized through contact angle measurements. The contact angle measurements were used to determine the hydrophilicity of the coated substrates.

Coated PDMS-based substrates with SA have a contact angle of 12̊ showing high hydrophilicity and adhesiveness, followed by PEG with a contact angle of 25,̊ whilst PLGA recorded a contact angle of 42.2̊ for PDMS (10:1). For PDMS (40:1), biopolymer coatings also show a SA contact angle of 18.2 ̊ followed by PEG with a contact angle of 26 ̊and the PLGA contact angle was 32.2.̊ There was a significant difference in the contact angle with the pre-stretched coatings. A pre-stretch contact angle of 8.5 ̊ was recorded for PEG, whilst SA was 36.7̊ for PDM (Fe3O4)10:1. Similarly, the contact angle for a pre-stretched PEG coating was 14.4 and SA was at 22.1̊ on PDM (Fe3O4) 20:1. SA coating was good for direct physical coating, whilst a PEG coating was good for pre-stretched coating. Also, the chemical modification improved whilst the boiling time decreased the contact angle as a result of creating a-OH bond. The PDMS-magnetite composites were found to induce heating for hyperthermia treatment. The surface’s wettability and roughness were then discussed to determine the implications of substrates to be used for cell culture. The modified surfaces gave indications of how cells would grow or how substrates would integrate in body tissues.

Keywords: Surface modification, polymeric biomaterials, tissue integration, contact angle, chemical modification

TABLE OF CONTENTS

CHAPTER ONE-14
1.1 INTRODUCTION-14
1.2 CURRENT CANCER TREATMENT METHODS AND CHALLENGES-14
1.3 BIOMATERIALS-15
1.4 REQUIREMENTS OF BIOMATERIALS USED AS IMPLANTS-15
1.5 PROBLEM STATEMENT-16
1.6 MOTIVATION OF RESEARCH-16
1.7 GOAL OF WORK-17
1.8 SCOPE OF WORK-17
CHAPTER TWO-19
LITERATURE REVIEW-19
2.1 INTRODUCTION-19
2.2 POLYDIMETHYL SILOXANE (PDMS) SUBSTRATES-19
2.3 SURFACE MODIFICATION AND CELL GROWTH-19
2.4 SURFACE PROPERTIES AND CELL GROWTH-20
2.5 MECHANICAL CHARACTERIZATION OF PDMS-21
2.6 METHODS FOR STUDYING CELL/SURFACE ADHESION-22
2.7 WETTABILITY AND CONTACT ANGLE-22
CHAPTER THREE-24
3.1 MATERIALS AND METHODS-24
3.1.1 MATERIALS-24
3.2 EXPERIMENTAL METHODS-24
3.2.1 Polymerization of PDMS-24
3.3 MODIFICATION OF PDMS-26
3.3.1 Chemical Modification of Samples-27
3.3.2 Surface Modification with Biopolymers-28
3.3.3 Pre-stretching-29
3.4 PREPARATION OF PHOSPHATE BUFFER SALINE-30
3.4.1 Optical Characterization of PDMS-30
3.5 DETERMINATION OF CONTACT ANGLE-30
CHAPTER FOUR-33
4.1 RESULTS AND DISCUSSIONS-33
4.2 INTRODUCTION-33
4.3 OPTICAL CHARACTERIZATION-33
4.3.1 Morphologies of Substrates Coated with Biopolymers-33
4.3.2 Effect of Coatings on PDMS: Fe3O4 Substrates-34
4.3.3 Effect of Pre-stretch on Surface Morphology-35
4.4 SURFACE ROUGHNESS-37
4.4.1 Effect of Fe3O4 on the Surface Roughness-38
4.4.2 Effect of PDMS (10:1)-Fe3O4 Surface Roughness due to Biopolymers Coated-38
4.4.3 Effect of Polymer Coatings on Surface Wettability-39
4.4.4 Wettability of PDMS-Based Nano-composites-42
4.4.5 Kinetics of Substrate Wettability via Chemical Modification-43
4.4.6 Effect of Physical Modifications on Substrate Wettability-46
CHAPTER FIVE-48
5.0 CONCLUSION AND RECOMMENDATION REMARK-48
5.1 CONCLUSION REMARKS-48
5.2 RECOMMENDATIONS REMARKS-49
Bibliography-50

CHAPTER ONE

1.1 INTRODUCTION

Cancer is the uninhibited growth of unusual cells in the body. Cancer presently remains the next prominent cause of death after heart disease [1, 2]. Research has revealed that there were 10 million new cases, 6 million deaths, and 22 million people living with cancer globally in the year 2000[3]. These statistics denote a rise of about 22% prevalence and death from that of the year 1990 [4]. It was estimated that the figure of new cases of all cancers globally would be 12.3 and 15.4 million in the year 2010 and 2020, correspondingly [3]. The treatment of cancer has drawn the attention of many physicians and scientists trying to fashion out treatment methods that can help solve the cancer problem.

1.2 CURRENT CANCER TREATMENT METHODS AND CHALLENGES

A present treatment method such as chemotherapy is a kind of cancer cure that administers drugs to kill cancer cells in the body. Chemotherapy does not only kill fast-growing cancer cells, but also kills or slows the progress of healthy cells that develop and divide rapidly.

Damage to cells can lead to severe side effects, such as mouth sores, nausea, and hair loss [5].

Radiation therapy is another cancer cure that practices high dosages of radiation to destroy the uninhibited growth of unusual cells in the body and shrink tumors [6]. Radiation kills or slows the advancement of uninhibited growth of unusual cells in the body, and it can also affect neighboring sound cells [6]. Injury to healthy cells can cause side effects such as fatigue, which is, feeling exhausted and worn out [6].

Surgery, when used to treat cancer, is a procedure in which a physician eliminates tumors in a patient’s body [5]. The above cancer treatment techniques with others such as home therapy, liposomes have severe side effects [6] and are costly for an average African [1]. This therefore calls for alternative treatment methods such as using microfluidic devices for localized drug delivery. However, issues of biocompatibility and surface modification of biomaterials are of great concern.

1.3 BIOMATERIALS

Medical implants can serve as life-saving and restoring means to the health of cancer patients[6]. A biomaterial can be defined as any material used to create a device to replace a part or a role of the body in a harmless, dependable, cost-effective, and functional satisfactory way.

Materials that are used for biomedical or medical uses are well-known as biomaterials. The key classes of biomaterials comprise; metals, ceramics, polymers, and composite materials [7]. Such materials are used as molded or machined parts, coatings, fibers, films, foams, and fabrics. Below is a chart on biomaterials summarized in Figure1.
Figure Summary of biomaterials.

1.4 REQUIREMENTS OF BIOMATERIALS USED AS IMPLANTS

Medical implants often do not adapt to the body tissues and sometimes are reject as foreign objects. However, our body can be trapped with the exact kind of material to make it compatible with biomaterial. The surface of an implant can be altered in several ways, enclosing; plasma modification [8]; ozone treatment [9], chemical modification [10], physical modification [11] and spread on coatings to the substrate [8]. Surface modifications can be used to disturb surface energy [12]; measure the disturbance of intermolecular bonds that arise when a surface is formed [12], and interface adhesion [13]. Adhesion is the affinity of different atoms or faces to adhere to one another [14].A biomaterial is therefore expected to possess the qualities of biocompatibility, chemical inertness, lubricity, sterility, asepsis, thrombogenicity, vulnerability to corrosion, deprivation, and hydrophilicity [15]

Implantable materials should confirm the biocompatibilities of material to perform with a suitable host reaction in a particular application [16].Thus, biocompatibility comprises the approval of a man-made implant by the neighboring tissues and by the entire body. A biocompatible implant, therefore, should not, infuriate the surrounding structures [17], incite an unusual provocative response [18], incite allergic reactions [19], and must be cancer free [20]. Other compatibility characteristics that may be important in the function of an implant device prepared as a biomaterial are sufficient mechanical properties such as strength; stiffness, and fatigue properties, suitable visual assets if the material is to be used in the eye, skin, or tooth and appropriate density [21].

1.5 PROBLEM STATEMENT

Bio-integration is an absolute requisite for a man-made implant. The connections at the interface between an implant and the host tissues should be treated to guarantee that they do not prompt any harmful effects such as prolonged inflammatory reaction or the establishment of abnormal tissues [22]. Among biomaterials, maximum polymeric materials fulfill the necessities to be used for biomedical usage. Polydimethylsiloxane (PDMS) has been used in the production of maximum biomedical devices comprising drug delivery devices [22].

However, most polymeric biomaterials such as PDMS are restricted in most cases by the nonsufficient bio-connection properties of the polymer [22]. Surface modification creates nanosize-microsize layers with controlled chemical structure, structure and roughness, and hydrophilic/hydrophobic balance emerge as a simple, useful, and adaptable method to answer the problem [23]. Knowing the process of cell surface interaction is very vital for the scheme of polymeric implants surfaces with enhanced bio-interaction possessions to improve cancer cure.

1.6 MOTIVATION OF RESEARCH

The motivation for this thesis was derived from the Soboyejo Group Focus. The group aimed at developing a multi-modal implants device for drug delivery. This drug delivery device has its surfaces made up of polydimethylsiloxane (PDMS). The problem of this PDMS is its hydrophobic surface. Therefore several surface modifications techniques need to be applied to overcome this problem of hydrophobicity. Possible modifications include making the surface hydrophilic by using oxygen-plasma [24], or bonding functional groups to the surface capable of supporting the home-made proteins, antibodies and mammalian cells [25]. The advantages of bonding functional groups to the surface overcome a constant problem with modified PDM surfaces in that; they tend to recover their original hydrophobicity [26].

1.7 GOAL OF WORK

This work will focus on the patterning and wettability of PDMS to control cell adhesion. Given this, several surface modification techniques will be employed to test the effect of cell growth on modified PDMS surfaces. The modified surfaces will guide the development of implantable biomedical devices for both hyperthermia and controlled drug delivery for cancer treatment.

1.8 SCOPE OF WORK

In order to meet the above goal, the research is to be carried out in the following steps:

 Polymerization of PDMS slabs will be done along with coating of substrates with various approaches (polyethylene glycol, sodium alginate, polylactic glycolic acid).

 Other surface modifications such as boiling in deionized water will also be investigated.

 Coating with a thin layer magnetite nanocomposite (made of PDMS:Fe3O4) to serve for both cell adhesion and also to ensure hyperthermia cell death.

 Pre-stretch effect and surface coating on PDMS substrate.

 Study the wettability of the PDMS modified surface using drop-water contact angle measurement.

 Breast cancer cells will be cultured to study cell viability and cell attachment on the various modified surfaces.

 The modified surfaces will be characterized through various techniques including:

 Fourier Transform Infrared (FTIR) Spectrophotometer to determine the functional groups on the modified PDMS,

 X-Ray Diffraction (XRD) techniques to check the crystallinity of the PDMS and also the chemical elements present in the modified surfaces,

 Use scanning electron microscope (SEM) to examine the morphologies of the modified substrate. EDS on the SEM can also be used to study the elementary analysis qualitatively.

 The implications of the results will be discussed for the design of an implantable biomedical device, with the right surface modification, for tissue integration.


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