It is known that normal wound healing involves the interaction of ECM proteins, such as fibrinogen, with fibroblasts.1 Fibrinogen, produced by the liver, is a plasma protein that is converted into an insoluble fibrin gel following a cut. This interaction not only results in the formation of a clot that will reduce blood loss but also appears to play a critical role in the tissue repair necessary to heal a wound. Each stage of wound healing in diabetics is impaired. The reasons for these impairments in diabetic wound healing are presently unclear. The objective of this research is to observe the effects of glucose on the human fibroblasts and their extra cellular matrix (ECM). In diabetics, excess glucose causes glycosylation, a reaction between glucose and the ECM, specifically its proteins, causing non healing wounds. Therefore, the structure of the fibroblast, as well as the ECM, at the sight of the wound is believed to change as a result of this reaction.
An in-vitro model of an ECM can be reproduced by spinning sulfonated polystyrene (SPS) 28% onto a silicon (Si) wafer.2 Since diabetes mellitus is diagnosed when levels of blood glucose are constantly 2 mg/ml or higher than normal physiologic levels, the effect of glycosylation on fibroblasats, fibrinogen, and the natural ECM can be studied by adding various concentrations of glucose to the solution (0, 1, 2, and 3 mg/ml).
At the 3 mg/ml glucose concentration, fibroblasts had a higher lateral response as measured by the AFM, indicating that these samples became softer than the control. The samples of fibrinogen at the 3 mg/ml glucose concentration hardened after the second day of incubation. However, as the incubation period increased, the fibers became softer as a result of excess glucose adsorbing on the surface. In conclusion, it is apparent that glycosylation is hardening proteins. Similarly, excess amounts of glucose significantly changed the mechanics of the cell. These mechanical differences might be responsible for impaired wound healing in diabetes. This study was supported by grants from the Simons Foundation.

1. Makogonenko, Evgeny, Tsurupa, G., Ingham, K., Medved, L. Interaction of
Fibrin(ogen) with Fibronectin: Further Characterization and Localization of the Fibronectin-Binding Site. Biochemistry 2002;41:7907-7913.

2. Pernodet N, Rafailovich M, Sokolov J, Xu D, Yang NL, McLeod K. Fibronectin fibrillogenesis on sulfonated polystyrene surfaces. J Biomed Mater Res. 2003; 15;64A(4):684-92.