Induction of Granulation Tissue Formation

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Induction of Granulation Tissue Formation
In 10 consecutive patients with large nonhealing ulcers caused by venous insufficiency (8) or vasculitis (2), portions of the ulcers were treated with hyaluronic acid, while the other portions were treated with a hydrogel. Wound size, time until a red granulating wound bed was achieved, total wound healing time, and number of required grafting procedures were recorded. Compared to control, time until grafting was reduced by 29 percent (p = 0.004), and total wound healing time was reduced by 31 percent (p = 0.0003). The hyaluronic acid-treated ulcers required six grafting procedures versus eleven in the control group.

Hyaluronan, a benzyl esterified hyaluronic acid derivative, is available as a nonwoven wound dressing. When it is applied to a wound, it hydrolyzes and provides a hyaluronan-rich environment. Hyaluronan, a linear polymer of glucuronic acid N-acetylglucosamine disaccharide, has been shown to be associated with multiple biological events in wound healing and promotes tissue repair and angiogenesis in experimental models. It is hypothesized that low molecular-weight hyaluronan oligo-saccharides stimulate endothelial cells through binding to ICAM-1 and induce cytokine production by macrophages and fibroblasts through binding to the CD44-receptor. Other observations, all from preclinical studies using cell cultures, tissue cultures, or animal studies, have been that hyaluronan induces angiogenesis, fibroblast migration and collagen deposition, keratinocyte proliferation and migration, and cell detachment and mitosis in general.

Several case reports and descriptive studies on the clinical use of hyaluronan have been published, but controlled clinical trials are scarce. Liguori, et al., performed a placebo-controlled study with hyaluronic acid cream in 134 patients treated with radiotherapy and concluded that hyaluronic acid reduced the incidence of high-grade radio-epithelitis. Ortonne compared hyaluronan to dextranomer paste in 50 patients with venous leg ulcers and found a significant reduction in wound size after three weeks of treatment (p < 0.001) in the hyaluronan-treated ulcers.

The purpose of this study was to find clinical evidence for the hypothesis that hyaluronan derivatives induce granulation tissue formation. Because hyaluronic acid gauzes form a gel after contact with wound fluid, another gel was used as control treatment.

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