Quantitative histomorphometry and quantitative polymerase chain reaction (PCR) as assessment tools for product development

In the current chapter, 12 normal, healthy subjects were enrolled in a clinical study to assess the efficacy of a topically delivered therapeutic to improve the health and appearance of skin. Clinical and histological assessments along with immunohistochemistry and gene expression results were evaluated using quantitative methods for a comprehensive determination of the therapeutic effect. As described in the previous chapter, coupling of various analytic tools in this way can allow for a more complete assessment of a therapeutic activity, a biomedical device's success, or a combination therapy's clinical benefit where a drug coating may be delivered to a targeted area using a biomedical device as a delivery system (e.g., drug eluting stents). The therapeutic evaluated in the current study was a topical dissolved oxygen dressing (OxygeneSys™ Continuous, AcryMed, Inc., Beaverton, OR). Clinical evaluations demonstrated that the dressing was well tolerated and several measures of skin health and integrity showed improvements compared to a control dressing site. Quantitative data from histology, immunohistochemistry, and gene expression studies demonstrated a general reduction in inflammatory response markers and transcription products (IL-6, IL-8, TNF-alpha, MMP-1, and MMP-12) while facilitating a general increase in structural skin proteins (collagen I, elastin, and filaggrin). Additionally, p53 signals from biopsy samples support the conclusion that the topical therapeutic presented no safety concerns. In summary, the data from this study demonstrated that the dressing had no deleterious effects and stimulated beneficial effects on intact, nonwounded skin. Additionally, quantitative histomorphometry and quantitative polymerase chain reaction (PCR) techniques provided unique tools to comprehensively assess clinical benefits.