## 5 Clinical Products Containing Hyaluronan Used for Wound Healing
By using ocenidine, a higher ratio of complete healing was observed after 8 weeks in chronic venous disease compared with dressings containing silver [178]. [PERSON] and collaborators tested the healing of chronic wounds with dressings made of HA/ocenidine (HA/OCT) with an SoC made of carboxymethyl cellulose/silver (Ag/CMC). Biopsies were taken at time 0, 2 or 6 weeks of treatment from two wound areas. CD68, a valuable cytochemical marker of inflamed tissues, was significantly lower in the wounds treated with HA/OCT than those treated with Ag/CMC. A significant decrease in granulocytes occurred after 2 weeks in the wounds that received HA/OCT treatment. The parts of the wounds treated with Ag/CMC exhibited significantly higher numbers of granulocytes. The expression of CD14, a marker of bacterial infection, was up-regulated in the wounds treated by Ag/CMC after 2 and 6 weeks [142]. A post-market clinical study reported a comparison of HA/OCT with SoC dressings containing silver. The clinical study included 48 patients using HA/OCT in the arm and 39 patients in the SoC arm. HA/OCT significantly reduced the wound area more than SoC. The patients observed a considerably decrease in pain [141]. As a common complication of diabetes, chronic wounds have a high incidence; due to expensive treatment, the recurrence of the pathologies causes long-term negative impacts on patients' quality of life. [PERSON] et al. reported the efficacy of an ointment based on HA/Collagenase (Bionect Start(r)) on patients affected by hard-to-heal ulcers (diabetes mellitus (n = 20), post-traumatic ulcers (n = 35), chronic burns degrees I and II (not healed in 12 weeks) (n = 10), and pressure ulcers (n = 5)). Patients with hard-to-heal wounds and necrotic tissue were included. The patients followed the same disinfection protocol and application of 2 mm of the ointment. The wound bed score was used to evaluate the data (black eschar, eczema/dermatitis, depth, scarring (fibrosis), the color of the wound bed, edema, resurfacing epithelium, and exudate amount). The clinical results showed a significant improvement in all the above-described parameters and pain reduction after two months of treatment. A reduction in bacteria in the wound was detected. At the end of the treatment, the bacterial pathogens were completely eliminated [179]. [PERSON] et al. published the results of six clinical studies involving 378 patients. The efficacy of Vulnamin(r) was evaluated according to a reduction in wound area, percentage of healing closure, or completed wound closure. The patients were divided into three groups: (i) Patients with alginate dressing; (ii) The HA/AA ointment under the alginate dressing; (iii) group 2 with an additional oral amino acid treatment. The treatment with the ointment (medical device made of HA + amino acids (AA)). The patients demonstrated a rapid wound size reduction and fast healing. With the reduction in dressing changes, a lower cost of the treatment was calculated as well as reduced infection risk in the patients [180]. Vulnamin(r) has been demonstrated to be effective in patients with difficult-to-treat wounds such as venous leg ulcer management or diabetic foot ulcer management. Hyalomatrix(r) PA is a bio-resorbable dermal substitute made of esterified HA (HYAFF), commonly used as a dermal substitute for chronic wounds of different etiologies (vascular ulcer, diabetic foot, traumatic wounds, or pressure ulcers), deep burns, and full-thickness burns [173]. The clinical trials showed that re-epithelialization was reached in 83% of ulcers after 16 days. 26% of wounds achieved 75% of re-epithelialization within the 60-day follow-up period using this treatment. A follow-up showed that 84% of ulcers achieved complete re-epithelialization by secondary intention [87]. This product was used in pediatric burned patients as a temporary dermal substitute to cover deep partial-thickness burns after dermat abrasion [181] and scalp wounds exposing dura or cranium [182]. [PERSON] et al.