The Effect of Control-released Basic Fibroblast Growth Factor in Wound Healing: Histological Analyses and Clinical Application.

High incidence of chronic wound including pressure ulcers and lower leg ulcers due to diabetes, ischemia, and so on represents a significant problem with few solutions. Particularly, in developed countries, it has been estimated that 1–2% of the population will experience a chronic wound during their lifetime and the associated costs are estimated to 2–4% of the total health care expenses.1 For such wounds, various therapeutic approaches have been developed based on the concept of regeneration medicine such as cell-based therapy and growth factor-based therapy.2–4 The fibroblast growth factors (FGFs) are a family of polypeptide that is mitogenic for a broad range of cell types and mediators of a wide spectrum of developmental and pathophysiological processes in vivo and in vitro.5,6 The basic FGF (bFGF), which is one of the 22 different isotypes of FGF, plays a crucial role in wound healing process by promoting fibroblast proliferation, inducing neovascularization, and increasing the synthesis of collagenase.7–10 As human recombinant bFGF has been commercially available in Japan, topical administration of bFGF has shown to be effective for wound healing in clinical situations.11,12 However, daily administration of bFGF is required for wound healing due to its short half-life in vivo, which occasionally is time-consuming and painful and/or results in discomfort for patients and a potential risk of infection. Gelatin is a denatured extract of collagen and has a biodegradable property. Recently, Tabata and coworkers13,14 have demonstrated a novel approach with a drug delivery system using gelatin that enabled controlled release of bFGF while it undergoes hydrolysis in vivo and thus improved efficacy of growth factor therapy. Thereafter, several preclinical and clinical studies have been conducted and shown that such control-released bFGFs contribute to healing process of many tissues and neovascularization.15–24 Therefore, the purpose of this study is to see whether bFGF-impregnated gelatin sheet is effective for wound healing compared with the conventional spraying administration in a murine model. In addition, we investigated the safety of such materials for the treatment of patients with skin ulcers.