A bell-shaped dose–response of topical FGF-1 in accelerating dermal wound healing in aged female BALB/cByJ mice

The objective of this study was to characterize the therapeutic dose–response characteristics for topical FGF-1 in the full-thickness dermal healing of aged female BALB/cByJ mice. The approach utilized a splinted excisional model of dermal healing, and a novel fine-sampled photographic methodology, to quantify key wound healing parameters for different doses of topical FGF-1. The histology of healed wounds, representative of each dose cohort, was also evaluated by section and staining. The results show that topical FGF-1 pharmacotherapy for accelerating dermal healing in aged BALB/cByJ female mice yields a narrow dose–response curve, with diminished therapeutic effect at high concentration (i.e., “bell-shaped” dose–response). The physiological response of FGF-1 in wound healing involves a combination of cell types (including vascular endothelial cells, epidermal keratinocytes and dermal fibroblasts). These individual cells types in culture can have different FGF-1 dose–response curves; however, only the response of fibroblasts is bell-shaped. The bell-shaped dose–response in dermal healing, therefore, principally reflects the effect upon fibroblasts. A narrow bell-shaped dose–response requires precise dosing of FGF-1 for therapeutic benefit. The results identify the practical dose range to elicit such a benefit.