David B. Hom

Angiogenic growth factors : their effects and potential in soft tissue wound healing

Since their discovery 30 years ago, angiogenic growth factors have been demonstrated to stimulate neovascularization in vitro and in animal studies. Over the last decade, knowledge gained in the field of angiogenic growth factors has grown immensely. These angiogenic growth factors exist in four major families: fibroblast growth factor (FGF), transforming growth factor beta (TGF-β), platelet-derived growth factor (PDGF), and epidermal growth factor (EGF). Each has the ability to induce soft tissue vascularization in microgram quantities. In animal models, FGF, TGF-β, PDGF, and EGF have been shown to enhance soft tissue wound healing. In human clinical trials, EGF and a mixture of PDGFs have been demonstrated to accelerate epidermal regeneration in cutaneous wounds. These factors have considerable therapeutic potential in the areas of soft tissue wound healing and otolaryngology. This article reviews important aspects of angiogenic growth factors and discusses their future potential in soft tissue wound healing.

Promoting Healing With Recombinant Human Platelet‐Derived Growth Factor–BB in a Previously Irradiated Problem Wound

Objectives/Hypothesis Persistent, poorly healing wounds are a significant clinical problem in patients who have had previous irradiation. Despite current treatments, refractory nonhealing soft tissue wounds persist. The study described one of the earliest reported uses of recombinant human platelet‐derived growth factor‐BB (rhPDGF) gel to improve the healing of a previously irradiated refractory dermal wound to the neck that had been present for 12 years.

Improving Surgical Wound Healing with Basic Fibroblast Growth Factor after Radiation

Objectives/Hypothesis: Delayed wound healing in surgical patients who have received previous irradiation continues to be a significant problem. We investigated whether radiation decreases basic fibroblast growth factor (bFGF) production in skin and whether supplemental bFGF can improve irradiated postsurgical soft tissue healing.

Choosing the optimal wound dressing for irradiated soft tissue wounds

This article reviews the healing state of the previously irradiated wound, the tenets for optimal wound care, and the choices of wound dressings now available for its management. The goal in assisting a previously irradiated surgical wound to heal is to transform its chronic wound state into an acute wound state. This transformation encourages wound healing to proceed. Six major moisture-retentive dressing categories exist to optimize its healing. They are classified into the alginates, foams, gauzes, hydrogels, hydrocolloids, and transparent films. Optimal wound care management for previously irradiated wounds involves (1) adequately debriding and cleansing the local wound, (2) accurately assessing the wound, (3) choosing the appropriate dressing based on the wound assessment, and (4) encouraging granulation tissue formation and reepithelialization.

The effects of tissue sealants, platelet gels, and growth factors on wound healing.

The improved understanding of wound healing has resulted in the rapid expansion of tissue adhesives, platelet gels, and the use of growth factors. Tissue sealants have been used to close incisions, seal and secure skin flaps, as well as promote hemostasis. Platelet gels have multiple uses that take advantage of their inherent clot-forming ability as well as their potential to release growth factors. Recombinant platelet-derived growth factor has been studied extensively for the treatment of chronic dermal ulcers and shows promise in enhancing wound care. This article will address some recent advancements related to the expanding use of tissue sealants and growth factors to enhance wound healing within the head and neck area.

GROWTH FACTORS AND WOUND HEALING IN OTOLARYNGOLOGY

An immense amount of knowledge has been gained over the last decade in the realm of polypeptide growth factors. Only recently has this new information made an impact in otolaryngology. This article Is a brief overview of peptide growth factors in relation to wound healing and otolaryngology.

EFFECTS OF NUTRITION ON WOUND HEALING

Optimal wound healing and Its close relationship to a patients positive nutritional balance is well known. For years, physicians have attempted to improve the metabolic status of patients after surgery or trauma. Currently, major emphasis is placed on perioperative nutritional status and its effect on postoperative wound healing. The intricacies of metabolism and healing are areas of current active research. In an effort to advance the quality of patient care. For the head and neck surgeon, wound healing is of paramount concern in areas of tumor extirpation, head and neck reconstruction, and maximization of postoperative functional recovery. To better explain why adequate nutrition is important in postoperative wound healing, we will provide a brief synopsis of nutrition and its relationship to wound healing.

Vascular Effects of Sustained-Release Fibroblast Growth Factors

Since the half-life of most angiogenic growth factors is several hours or less, sustained-release delivery would be optimal for their future clinical use. Two fibroblast growth factors, basic fibroblast growth factor (bFGF) and endothelial cell growth factor (ECGF), were delivered in two sustained-released modalities (poloxamer 407 and a gelatin sponge [Gelfoam]) to attempt to increase soft tissue vascularity. In vitro bioactivity of ECGF-poloxamer formulations was also tested on endothelial cell cultures. Among vascular-compromised skin flaps in rabbits, ECGF-poloxamer (N = 26), bFGF-poloxamer (N = 5), ECGF-poloxamer (N = 9, irradiated), and bFGF-Gelfoam flaps (N = 22) did not demonstrate significant differences in viability and vascularity compared to controls (p > .05). Irradiation had a detrimental effect on both flap vascularity and viability (p = .02). Future efforts for sustained delivery of angiogenic proteins are critical in order to make them clinically useful in wound healing.

Effects of angiogenic growth factors and a penetrance enhancer on composite grafts

Skin-cartilage composite grafts are invaluable tissues used in facial reconstruction, yet their survival is unpredictable beyond a 1-cm diameter. In this study, the angiogenic growth factors basic fibroblast growth factor (bFGF) and endothelial cell growth factor (ECGF) and a penetrance enhancer (dimethyl sulfoxide [DMSO]) were applied to composite grafts to determine their effects on survival and vascularization. We applied ECGF, bFGF, and DMSO either topically or by intradermal injection to 120 auricular composite grafts (3.0 cm diameter) in New Zealand White rabbits. Dermabrasion was performed in 2 groups to attempt to increase transdermal delivery. Graft viability and vascularity were evaluated 3 weeks later by template analysis and angiography. In the results, ECGF and bFGF, when grouped together, had a 40% increase in vascular ingrowth as compared to controls (p < .001). However, neither ECGF nor bFGF increased graft survival. A coincidental finding was that DMSO with dermabrasion significantly improved graft viability (>100%) with or without an angiogenic agent (p < .02). The potential of DMSO with dermabrasion to increase composite graft viability warrants further investigation.

Vascular and Epidermal Effects of Fibroblast Growth Factor on Irradiated and Nonirradiated Skin Flaps

Head and neck cancer surgeons are often faced with the challenge of managing previously irradiated soft tissue that has poor vascularity and slower epithelialization. This study investigates the effect of supplemental basic fibroblast growth factor (bFGF) on flap vascularity, tissue oxygenation, and epidermal regeneration in nonirradiated (n = 40) and irradiated porcine skin flaps (n = 40). Supplemental bFGF increased vascularity in nonirradiated flaps by 80% (p = .005), with a trend to a higher tissue oxygen level by day 14. The irradiated bFGF-treated flaps did not show increased vascularity or higher tissue oxygen levels 2 weeks after surgery. However, in both irradiated and nonirradiated groups, epidermal regeneration increased by greater than 70% with supplemental bFGF (p lt; .002). The results of this study suggest that supplemental bFGF can increase tissue vascularity in nonirradiated tissues and epidermal regeneration in both nonirradiated and irradiated conditions.