The application of atomic force microscopy in the surface analysis of polymeric biomaterials

Shakesheff, Kevin (1995) The application of atomic force microscopy in the surface analysis of polymeric biomaterials. PhD thesis, University of Nottingham.

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Abstract

When a polymeric biomaterial is employed within a living system an interface is created between the solid surface of the polymer and an aqueous environment. The processes that occur at this interface will determine if the biomaterial is accepted by the patient and often will determine if the specific function of the biomaterial can be achieved. Increasingly, novel biomaterials are expected to perform more sophisticated functions and, therefore, their surfaces must be designed to realize precise interfacial events, such as specific interactions with proteins and cells or controlled biodegradation.

To design polymeric biomaterials with specific surface properties it is necessary to develop surface analytical techniques that can accurately characterize these properties. The work described in this thesis has aimed to investigate the potential contribution of the atomic force microscope (AFM) to this characterization.

The advantages of utilizing AFM in the study of polymeric biomaterials lie in the ability of the instrument to visualize insulating surfaces at a high resolution within a variety of environments, including gaseous and liquid environments. Therefore, it is possible to image the nanoscopic organization of polymeric biomaterials within environmental conditions that are similar to the conditions encountered within living systems.

Initial studies have concentrated on imaging the surface morphology of poly(ethylane oxide) (PEG) samples in air. These studies highlighted the high resolution capability of the AFM on untreated polymer samples. On sphemlitic samples, the AFM has visualized the lamellar organization of crystalline fibres. These lamellae had widths of between 10 and 30 nm and height variations of less than 15 nm. The ability of the AFM to resolve such structures, without the introduction of an etching or staining procedure required by transmission electron microscopy, relies on the sensitivity of the instrument to changes in the height of the topography. This sensitivity has been further utilized to image polymer strands with recorded widths of 8 nm. This width represents an overestimation of the true dimensions of the strand due to the finite size of the AFM probe apex and using the circular probe model it has been calculated that the strands have true widths of less than 0.8 nm, indicating that they are composed of one or two PEG molecules. Further studies on PEG have demonstrated the ability to control polymer surface morphology through changes in the temperature of thin film preparation and changes in the method of polymer solution deposition.

The work on PEG surface morphology acts as the foundation for the remaining studies, which employ the AFM to study biodegradable polymers within aqueous environments. This in situ application of the AFM has recorded the changes in surface morphology that occur to poly(sebacic anhydride) (PSA) during surface erosion in alkaline conditions. These studies have visualized the preferential degradation of amorphous regions of sphemlites over the crystalline fibres for solution cast and melt-crystallized samples. It has been found that rapid cooling during the solidification of PSA increases the amount of amorphous material at the surface of samples. However, once this outer layer has been eroded the underlying material is dominated by crystalline fibres. In situ AFM studies have also demonstrated the pH dependence of the rate of PSA surface erosion.

The AFM techniques developed to visualize the evolution of surface changes during PSA erosion have then been employed to investigate the degradation of immiscible blends of PSA and the polyester poly(DL-lactic acid) (PLA). PLA degrades at a slower rate than PSA and therefore, as these blends eroded the surface morphology became dominated by PLA, revealing the phase separation of the material. For solution cast samples on mica substrates it was found that at high PSA content the PSA formed a continuous network around islands of PLA. However, as the relative content of PLA increased the morphology reversed and the PLA formed the network around islands of PSA.

The interest in studying biodegradable polymers is derived from their application in surface eroding drug delivery systems. Having demonstrated the potential of the AFM to visualize dynamic interfacial changes occurring to these polymeric biomaterials, the in situ studies were extended to investigate the release of a model protein drug from a degrading polymer film. The system under investigation was a poly(ortho ester) film containing particles of bovine serum albumin. The AFM visualized the initiation of dissolution of some protein particles within minutes of the exposure of the sample to a pH 6 environment. Other particles, however, displayed retarded dissolution behaviour and did not appear to dissolve until the sample had been exposed to the pH 6 environment for over 1 hour. To assist the interpretation of these studies computational methods of calculating changes in volume during polymer degradation and protein dissolution have been developed on the Genesis II system.

In the final experiments of this thesis, the application of a novel combined atomic force microscopy/surface plasmon resonance instrument is described. This instrument allows the simultaneous acquisition of topographical data by the AFM and kinetic data by the surface plasmon resonance instrument (SPR). The instrument is first applied to a simple poly(ortho ester) system to demonstrate that the changes surface morphology and polymer film thickness can be simultaneously monitored. Then, the PSA/PLA blends were re-analysed. This analysis highlighted the synergistic information obtained by the combined AFM/SPR and revealed new data on the relationship between polymer phase separation and biodegradation kinetics.

NB. This ethesis has been created by scanning the typescript original and may contain inaccuracies. In case of difficulty, please refer to the original text.

Item Type:Thesis (PhD)
Uncontrolled Keywords:Biomedical materials, Biomaterials, Surfaces, Surface chemistry, Atomic force microscopy, AFM, Drug delivery systems.
Faculties/Schools:UK Campuses > Faculty of Science > School of Pharmacy
ID Code:354
Deposited By:Business Library
Deposited On:24 Oct 2007
Last Modified:09 Apr 2009 12:55

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