Abstract: Methods are described using a particular type of assay system, the Multi-Pathway High Throughput Assay, in conjunction with a novel experimental strategy, whereby repeated cycles of experiments result in the identification of the most effective synergistic combinations of potential active agents from a library of materials. The novel experimental strategy not only requires far fewer total experiments than would be required using conventional discovery strategies but also maximizes the probability of finding highly synergistic combinations through the principle of multiple-pathway intervention.

Abstract: Methods are described using a particular type of assay system, the Multi-Pathway High Throughput Assay, in conjunction with a novel experimental strategy, whereby repeated cycles of experiments result in the identification of the most effective synergistic combinations of potential active agents from a library of materials. The novel experimental strategy not only requires far fewer total experiments than would be required using conventional discovery strategies but also maximizes the probability of finding highly synergistic combinations through the principle of multiple-pathway intervention.

Abstract: The method employs a piece of skin of area greater than 1 cm2 cultured under conditions that maintain its viability and substantially normal structure for sufficient time for topically applied test material to potentially exert an effect. The skin includes the majority of the epidermal layer plus an appropriate amount of supporting dermis. The surface of the skin is partitioned by a surface barrier film into a pattern of isolated regions to which different test materials can be subsequently topically applied in such a way that they do not significantly migrate around the edges of the skin into the culture medium. The effect of the topically applied material on the skin is determined using an appropriate method. In a variant of the method, the temperature of the culture system is maintained at or below about 30° C. to improve the skins viability and maintain a substantially normal structure. The invention encompasses effective topically applied materials identified using the methods described herein.