Contribution of Topical Agents such as Hyaluronic Acid and Silver Sulfadiazine to Wound Healing and Management of Bacterial Biofilm

Abstract

Background and Objectives: Wound healing is commonly associated with critical bacterial colonization or bacterial infection, which induces prolonged inflammation, resulting in delayed re-epithelialization. An appropriate wound dressing requires a humid environment, which also functions as a barrier against bacterial contamination and will accelerate a regenerative response of the wound. Silver sulfadiazine (SSD) is used to prevent wound infection. Hyaluronic acid (HA) is an extracellular matrix component involved in tissue regeneration. This retrospective study was conducted to evaluate the effectiveness of cream and gauze pads based on hyaluronic acid at low molecular weight (200 kDa) and silver sulfadiazine 1% in the wound healing process. In addition, we examined SSD action on biofilms in vitro and on animal wounds, obtaining positive outcomes therefrom. Materials and Methods: We selected 80 patients with complicated chronic wounds of different etiologies, including diabetes mellitus (10), post-traumatic ulcers (45), burns (15), and superficial abrasion (10). Results: After 8 weeks, ulcer size was decreased in 95 ± 2% of the treated patients; a significant reduction in the inflammatory process was observed from day 14 onwards (p < 0.01 vs. baseline), considering improvement of the surrounding skin and reduction of the bacterial load. The SSD treatment decreased bacterial colony proliferation, both in planktonic state and in biofilm, in a dose-dependent manner on the wound but inhibited the development of tissue granulation at the highest dose (800 μg/wound). Conclusions: In conclusion, the combined action of SSD and HA is clinically effective in improving wound healing.

Keywords: antisepsis; chronic wounds; hyaluronic acid; silver; sulfadiazine; wound infections.

Figure 1

Progression of wound healing during the treatment with an ointment based on hyaluronic acid and silver sulfadiazine, as measured by the mean wound surface area and the overall mean percentage of granulation tissue. The mean wound surface area decrease is inversely proportional to the increase in the percentage of granulation tissue.

Figure 2

Bacterial load at each visit (log10 CFU/mL). For each box plot, the median values are represented by the line within the box. The box represents 50% of the values (the 25th and 75th centiles), with the bars indicating the highest and lowest values excluding the outliers. * is p value.

Figure 3

Evaluation of the quality of the wound-surrounding skin during treatment applications by the HPS score. All wounds progressively changed from class 3 to class 1 after 4 weeks.

Figure 4

Evaluation of peri-wound inflammation, erythema, purpura, oedema. After 2 weeks, 45% of the treated ulcers showed an improvement in the four parameters analyzed, and at 4 weeks, 74% of the treated ulcers showed further improvement in the four parameters compared to baseline.

Figure 5

Post-traumatic case. AC, 52 y/o. Presence of periwound inflammation signs and Class 3 periwound tissue according to HPS classification. Appearance of the wound after injury (A). Application of the Connettivina Plus ointment (B). Wound aspect after 2 weeks (C) and final aspect with complete reepithelialization after 8 weeks (D).

Figure 6

Diabetic case. AA, 58 y/o. Presence of periwound inflammation sign and Class 3 periwound tissue by HPS classification. Appearance of the wound before the treatment (A). Wound aspect after 2 weeks (B). Wound aspect after 4 weeks (C) and final aspect with partial reepithelialization after 8 weeks (D).

Figure 7

Burn case. MR, 70 y/o. Presence of periwound inflammation sign and Class 3 periwound tissue by HPS classification. Appearance of the wound before the treatment (A). Wound aspect after 2 weeks (B). Wound aspect after 4 weeks (C) and final aspect with complete reepithelialization after 8 weeks (D). Good motor function of the hand (E,F).

Figure 8

The effects of SSD on S. aureus-infected wounds in mice. S. aureus (SA) was inoculated 3 days after back skin excision, and SSD in different doses was applied onto the wound surface on day 4. Wound tissues stained by Gram + HE staining are shown on day 6. G: granulation tissue; bars = 100 μm.