Surgery and radiation therapy are frequently combined modalities for treating patients with head and neck cancer. Unfortunately, following surgery, wound healing is significantly impaired in previously irradiated soft tissue. This impaired healing from delayed vascularization and collagen production contributes significantly to patient morbidity and mortality. Any localized trauma, surgery, or infection to the skin or mucosa of an irradiated patient can precipitate into a major nonhealing wound. Recently, the potential to promote healing in irradiated damaged tissue with basic fibroblast growth factor (bFGF) with and without hyperbaric oxygen (HBO) has been described. However, it remains unknown under what tissue oxygen conditions bFGF has its greatest effect on vascularization and collagen deposition. The investigators hypothesize that previously irradiated soft tissue has altered bFGF production and bFGF levels in skin compared to nonirradiated tissue. They also hypothesize that the administration of HBO to irradiated tissue will change bFGF production and its protein in irradiated tissue. Next, they hypothesize that the effect of supplemental bFGF will alter the vasculature and collagen in the setting of HBO in irradiated tissue. The porcine skin flap model will be used since its dermis is most analogous to human skin in vascular anatomy and response to radiation. The following studies are specifically designed to investigate the effects of bFGF in irradiated wounds under different tissue oxygen conditions.
Aim I will determine if bFGF production and protein are altered in previously irradiated tissue compared to nonirradiated tissue. Also, it will be demonstrated if HBO effects bFGF expression and production under both conditions. Basic FGF in skin flaps will be evaluated by the RNAse protection assay and by immunohistology. Basic FGF production will be quantitatively compared between irradiated, nonirradiated, HBO and non HBO groups.
In Aim 2, the collagen effects of supplemental bFGF among irradiated, nonirradiated, HBO and non HBO flaps will be determined by collagen concentration, tensile strength and collagen staining techniques.
In Aim 3, the vascular effects of supplemental bFGF to skin flaps will be evaluated by angiography and subcutaneous tissue oxygen measurements in the settings of radiation and HBO.
In Aim 4, the viability and vascular effects of supplemental bFGF to irradiated and nonirradiated ischemic flaps will be determined under normal and hyperbaric conditions. A better understanding of bFGF in irradiated tissues would permit therapeutic intervention that would decrease patient mortality and morbidity in these difficult to manage wounds.
| Hom, David B; Unger, Gretchen M; Pernell, Kerri J et al. (2005) Improving surgical wound healing with basic fibroblast growth factor after radiation. Laryngoscope 115:412-22 |
| Hom, D B; Simplot, T C; Pernell, K J et al. (2000) Vascular and epidermal effects of fibroblast growth factor on irradiated and nonirradiated skin flaps. Ann Otol Rhinol Laryngol 109:667-75 |
| Hom, D B (2000) A new era of discovery in facial plastic surgery. Arch Facial Plast Surg 2:166-72 |
