Chapter 1. Introduction and literature review
1.1 Biocompatibility
Biocompatibility is an essential requirement for materials designed to be employed for biomedical applications. Among all characteristics, the cytotoxicity and hemocomptibility are the most concerned ones for biological-contacting materials.
When materials exposed to biological systems, whether in vivo and in vitro, complex interactions will be raised, which have always been challenges for developing novel biomaterials.[1] Therefore, scientists and bioengineers were searching for non-immunogenic, low biological toxic and physiological compatible materials which related to both their bulk and surface properties. Moreover, while the bulk properties include mainly mechanical, optical properties and thermal property, surface properties (for instance, wettability, functionality, and morphology) are more intensely contacting with organisms. Moreover, cells, proteins, and other cellular components interact with material surfaces immediately when materials contacted to in biological systems. The surface-triggered responses mainly resulted from surface property and have lasting impacts on the efficient of biomedical devices. Therefore, surface modifications are extensively utilized to promote biocompatibility.
Beside interactions between materials and cellular compounds, biomedical devices are much further contacted with blood. When biomedical devices contact with blood, interaction begins with protein adsorption, following by platelet adhesion, blood coagulation, and finalized by thrombin formation. Therefore, blood compatibility becomes an important and necessary issue for biomaterials. T-cell immunogenic, blood coagulation and thrombin formation lower the efficiency of biomedical devices and thus become a risk for biomedical applications. Furthermore, with intensive development and progress of organs transplant technology and artificial
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tissues research, requirements for non platelets adhered devices and membranes are rapidly increasing.
In the last decade, many studies had shown that effect of thrombin formation and coagulation could be reduced by heparin incorporation onto surface.[2] PU are widespread applied in bioengineering, biomedicine, and biomedical fields for its well-known mechanical property.[6] Nevertheless, undesirable bioreactons such as biofouling and thrombogenic reaction have to be eliminated before further applied.
PDMS, commonly utilized in biomembrane applications for it hydrophobic character.
Recently, some polymers such as PEG and HEMA were proven to posse inhibition of platelet adhesion. As a result, promoting biocompatibility not only increases potential use for biomedical applications but also benefit human beings life.
1.2 Polyethylene glycol
PEG (polyethylene glycol) with repeating unit of –CH2CH2O is widespread utilized in various industry fields, such as food, pharmacy, and biochemistry applications.[3] Its advantages of non-immune, high aqueous solubility, low toxicity have commonly been regarded as a high biological compatible biomaterial.
Moreover, anti-fouling effect makes PEG to be more suitable for potential utilization in biomedical field. The reason for its anti-fouling effect of PEG is the polar functional group provides surface with hydrophilic character, which then contribute to the anti-fouling effect. Some derivatives of PEG also demonstrated to exhibit biofouling resistance property, which stimulating extensive and abundant researches in study proteins resistance phenomena of PEG.
Mechanisms for anti-fouling effect of PEG are mainly due to the polymer coil and the random motion of PEG side chains.[4] The coil of PEG polymer twist each other thus create the resistance to protein. Random motion and fluctuation of its side
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chains also increase the resistance against protein adhesion.
1.3 Surface modification
Surface modifications are widely applied to functionalize material surfaces in order to acquire certain desired surface characters. Mainly, surface modification is categorized to wet process and dry process. In the wet process manufacturing, the materials were being immersed in chemical solvent to alter surface properties. It is a very convenient and simple surface modification method. However, environmental- concerned issues about toxic compounds and uneven concentration distribution during process have become undesired disadvantages. Moreover, the difficulty in spatial control for the modified spot is also another disadvantage.
Dry processes, which are including flame treatment, corona discharge, and plasma treatment, have attracted a lot of attentions in this decade. Low toxicity and rapid procedure are the core benefit. Besides, this process offers high degree of spatial control. Modified area can be ranged from one single spot to the whole surface.
Furthermore, dry process serves an environment friendly way in comparison with the wet process.
Photochemistry provides a brand new and useful way to deal with surface as photoreactive chemicals are easy to bond with various substrates in respond to UV irradiation.[5] This technology is employed in photo-immobilization where photoreactive species is able to form stable covalent bond with hydrocarbon polymers.
In addition, its rapid, inexpensive, and environmentally friendly process is due to simple ultraviolet light is required for incepting photoreaction. As a result, this versatile and facile surface modification found its application in field of microarray fabrication.
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1.4 Research goal
In this study, a novel copolymer, which originated from co-polymerization of PEGMA and AA, was synthesized to improve biocompatibility, especially blood compatibility. PEGMA was chosen for its anti-fouling feature whereas AA is commonly utilized in biomaterials. Azidoaniline (Az) was utilized in this PEGMA-AA copolymerization for purpose of increasing photoreactivity (Figure 1).
This Az-PEGMA-AA copolymer was characterized by employing several methods such as gel permeation chromatography (GPC), Fourier transform infrared spectroscopy (FT-IR), water contact angle (WCA), and nuclear magnetic resonance (NMR) to confirm that the polymerization was successfully proceeded. Moreover, LDH assay is aid to analyze the amount of platelets adhered to surface, namely blood compatibility. Furthermore, various substrates are also investigated for LDH assay with view to increase versatility of Az-PEGMA-AA copolymer.
Figure 1. The schematic route for the synthesis of Az-PEGMA-AA
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Chapter 2. Experimental