Formation of ferric ion-tannic acid complex films and its application to surface coating of functional cells

Abstract

Surface modification has been widely used as a useful method for controlling the surface properties of various materials. However, the chemical characteristics of the surface were different for each substance, and the chemical interactions required for the modification should be different. Thus, for a certain modification method, the surface to which it can be applied was limited, and some materials were difficult to modify. In this situation, there is a need for a modification method that does not depend on the surface characteristics, and the substrate-independent modification method using catechol and galloyl groups capable of various chemical interactions with various surfaces has been proposed.

Tannic acid (TA), a type of polyphenol found in nature, has recently been reported to form nanometer-thick films (< 100 nm) with adhesion to various surfaces through coordination with ferric ions ($Fe^III$). The $Fe^III$-TA complex thin film has a merit that it is very rapid and easy to form compared to other surface modification methods. Due to the reversible nature of the coordination bond, degradation of the film was also possible by treatment with an acidic solution or a chelating ligand (EDTA).

In this thesis, we first studied the formation of a $Fe^III$-TA thin film with the presence of a salt. Unlike pure water, the thickness of the $Fe^III$-TA complex thin film was found to increase with time in the salt solution, which was confirmed to be influenced by the concentration and kind of salt. The salts consist of cations and anions, of which the effect of the anions is negligible and most of the effects came from the cations. The larger the cation charge, and the smaller the cation size if the cation charge is the same, the more effectively the thin film could be formed.

Second, a thin film of $Fe^III$-TA complex was formed on the surface of red blood cells to make it resistant to the attack of antibodies while maintaining the oxygen-carrying ability of red blood cells. Since the antigens causing the immune reaction upon transfusion are present on the surface of the red blood cells, they can be shielded by surface coating, which would inhibit the immune response by blocking the antigen-antibody interactions. Since red blood cells are very sensitive to the salt concentration, we needed to use isotonic saline in the whole coating process and optimize other coating conditions. As a result, it was confirmed that a thin film of $Fe^III$-TA complex having a thickness of 20 nm was formed on the surface of red blood cells, which successfully prevented cell aggregation by antibody treatment.

Thirdly, we developed a method to reduce the immune response in the transplantation by forming the $Fe^III$-TA complex thin film on the pancreatic islet cell surface. Pancreatic islet transplantation in patients with type 1 diabetes has the advantage of eliminating the need for periodic insulin injections, but there have been side effects such as the immune rejection causing the transplanted cells to last for a short time. The pancreatic islets coated with a cell-friendly substance cannot be recognized as foreign cells in the body when transplanted, thus reducing the immune rejection. The pancreatic islet cells coated with the $Fe^III$-TA complex thin film maintained viability at a level similar to that before coating, and further studies on the immune response are needed to verify the effectiveness of the coating.