If sufficient silver ions are made available after the second reaction, a third reaction begins to take place. The third reaction constitutes a specific physical association of at least some of the silver ions with the collagen fibers present in the wound to produce a unique structure ("silver-collagen complex") having the specific properties required to induce activation of the de-differentiated fibroblast cells previously produced in the second reaction.
Collagen fibers have size-specific sites which are capable of forming a complex with hydrated metallic ions (J. A. Spadaro, et al., "Size-Specific Metal Complexing Sites in Native Collagen," Nature, Vol. 225, pp. 1134-1136 (1970)). The copper/collagen complex, in particular, has a unique electrical field which is involved in the initial epitaxial deposition of bone mineral (apatite) on bone collagen (A. A. Marino, et al., "Evidence of Epitaxy in the Formation of Collagen and Apatite," Nature, Vol. 226, pp. 652-653 (1970)). While not wishing to be bound by theory, it is believed that a silver-collagen complex according to the present invention has a unique local electrical field, and acts as a biological inducer to activate the de-differentiated fibroblast cells formed in the above-described second reaction. In mammalian wounds (including human wounds) treated at appropriate specific voltages with an excess of electrically generated silver ions, the formation of this silver-collagen inducer complex results in activation of the de-differentiated embryonic cells formed by the action of the silver ions on the pre-existing mature cells. Together, these effects result in cell behavior and action akin to those observed in animals that are capable of regeneration. In this fashion, an adequate blastema to support regeneration is formed in human tissue.
The above-described factors are designed to maximize the amount of silver ions introduced into the wound during the window wherein the above-described reactions can occur and lead to the formation of an adequate blastema for regeneration--a necessary condition for completing the sequence of three reactions within a biologically appropriate time.
In the first reaction, the silver ions combine with proteins, peptides and other chemical species normally present in solution in the tissues. Further chemical or physiochemical combinations do not occur until all such simple sites are completely filled. The first reaction typically requires approximately 24 hours to go to completion (wherein the term "completion" refers to saturation of available sites). The antibacterial action of silver ions is a result of this type of process, beginning at about 20-30 minutes following exposure of the bacteria to the ions.
If more free silver ions are made available following the first reaction, the second reaction occurs. The second reaction is an association between the silver ions and sensitive cells present in the wound, resulting in de-differentiation of these cells into embryonic cell types (as used herein, the term "sensitive cells" refers to cells that are sensitive to free silver ions, including, among others, mature fibroblast cells and epithelial cells). These embryonic cells are not activated in the sense that they do not multiply to produce additional cells of the same type; however, they are capable of re-differentiation into other cell types. Hence, these cells do not form an adequate blastema mass to produce organized, multi-tissue regeneration. Production of de-differentiated fibroblasts requires a continuous supply of excess silver ions for at least approximately 48-72 hours following saturation of the active chemical sites in the first reaction ("excess" in this context means that more silver ions are supplied than are needed to combine with all available proteins, peptides, etc. in the above-described first reaction).
FIG. 1 is a flow chart showing three sequential reaction processes resulting from the action of electrically-injected silver ions;
