Modulation of host responses to biomaterials by surface modification of layer-by-layer polyelectrolyte multilayers
Date Issued
2009
Date
2009
Author(s)
Hu, Fang-Wei
Abstract
It is well known that long-term artificial implants frequently failed to turn on normal healing process, but were encapsulated by a thick, fibrous collagen layer, known as foreign body reaction (FBR). Attempts to prevent FBR to artificial implants have been the focus of many studies. Recently, a simple and versatile method based on electrostatic attractions between oppositely-charged polyelectrolytes shows its potential for peptide immobilization. This technique of layer-by-layer (LBL) polyelectrolyte multilayer (PEM) deposition is based on the alternate adsorption of positively and negatively charged polyelectrolytes to build an ultra-thin film onto a substratum. The aim of this work is to apply this surface modification technique for improving host response to implants. In the first part, PDMS samples were alternatively adsorbed in variant solutions at pH 4 acetate buffer to build the multilayer films. The formed substrates were tested in vitro and in vivo models for evaluating biocompatibility. Macrophage-like cells, RAW 264.7 murine macrophage / monocyte cells were applied in our study. The cell numbers and NO production were decreased on the PDMS precoated with 20 bilayers of COL/HA compared to the unmodified PDMS. Cell morphology on the unmodified PDMS was spread, while that on the LBL modified PDMS was aggregated and rounded. No sign of cytotoxicity of the LBL films was found on. These results were discussed, and we contributed these effects to the biological function of COL or HA. The COL/HA modified PDMS was implanted subcutaneously in rats and explanted after 3 or 6 weeks. Preliminary results indicated that LBL-modified surface elicited a thinner collagen encapsulation compared to the unmodified samples. or the second part, we fixed the number of bilayers at 10, and investigate the factor of pH and species of polycations. Result indicated PLL/HA built at pH 10 were with a lowest cell number while it was proven due to the cytotoxicity which might result from PLL by both live and dead staining and activation test. We kept on searching other surfaces of multilayer films while they were assembled at pH 4 buffers instead of neutral or higher pH values in later experiments. Both synthesized and natural polymers were used. Results showed there were fewer RAW 264.7 cells on PEM composed of specific natural polycations and the performance could be varied by condition of construction such as salt concentration and adsorbed species of the top. Activation test revealed that surfaces with fewer cells brought about lower level of NO production. The NO production on some of them was even lower than the PDMS control without LPS. Surfaces with prefer expression were implanted, and preliminary results indicated these surface had a reduced capsule formation as previous. In conclusion, the technique of LBL deposition shows a potential to improve the biocompatibility of implants.
Subjects
biocompatibility
foreign body reaction
macrophage
polyelectrolyte multilayered film
nitric oxide
Type
thesis
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