Development of a wound dressing composed of a hyaluronic acid sponge containing arginine

Spongy sheets composed of cross-linked high-molecular-weight (HMW) hyaluronic acid (HA) were prepared by freeze-drying an aqueous HMW-HA solution containing cross-linking agent (Group I). The Group I sheet was immersed into an aqueous low-molecular-weight (LMW) HA solution with or without L-arginine (Arg) and was then freeze-dried to prepare several types of spongy sheets (Groups II-V). The amount of Arg was 1.0 g, 0.5 g, 0.2 g and 0 g in Groups III, IV, V and II, respectively. In the first experiment, each spongy sheet was applied to a full-thickness skin defect with a diameter of 35 mm in the abdominal region of SD rats, with intact skin in the central area measuring 15 mm in diameter. Commercially available polyurethane film dressing was applied over each spongy sheet as a covering material. The control group was covered with polyurethane film dressing alone. All spongy sheets promoted epithelization, as well as angiogenesis, as compared with controls. These findings indicate that HA and Arg are essential for wound healing. Re-epithelizaion was particularly active in Groups IV and V. In the second experiment, each spongy sheet was applied to a full-thickness burn injury measuring 35 mm in diameter in the abdominal region of SD rats, after necrotic skin was surgically removed. Groups II-V showed decreased wound size when compared with Group I and controls. The present findings indicate that the release of LMW-HA and Arg from a cross-linked HMW-HA spongy sheet effectively stimulates wound healing.