Dressings and topical agents containing hyaluronic acid for chronic wound healing

Hyaluronic acid is synthesised in plasma membranes and can be found in extracellular tissues. It has been suggested that the application of hyaluronic acid to chronic wounds may promote healing, and the mechanism may be due to its ability to maintain a moist wound environment which helps cell migration in the wound bed.

To evaluate the effects of hyaluronic acid (and its derivatives) on the healing of chronic wounds.

We used standard, extensive Cochrane search methods. The latest search date was February 2022.

We included randomised controlled trials that compared the effects of hyaluronic acid (as a dressing or topical agent) with other dressings on the healing of pressure, venous, arterial, or mixed-aetiology ulcers and foot ulcers in people with diabetes.

We used standard methodological procedures expected by Cochrane. We assessed the certainty of the evidence using the GRADE approach.

We included 12 trials (13 articles) in a qualitative synthesis, and were able to combine data from four trials in a quantitative analysis. Overall, the included trials involved 1108 participants (mean age 69.60 years) presenting 178 pressure ulcers, 54 diabetic foot ulcers, and 896 leg ulcers. Sex was reported for 1022 participants (57.24% female). Pressure ulcers It is uncertain whether there is a difference in complete healing (risk ratio (RR) 1.17, 95% confidence interval (CI) 0.58 to 2.35); change in ulcer size (mean difference (MD) 25.60, 95% CI 6.18 to 45.02); or adverse events (none reported) between platelet-rich growth factor (PRGF) + hyaluronic acid and PRGF because the certainty of evidence is very low (1 trial, 65 participants). It is also uncertain whether there is a difference in complete healing between lysine hyaluronate and sodium hyaluronate because the certainty of evidence is very low (RR 2.50, 95% CI 0.71 to 8.83; 1 trial, 14 ulcers from 10 participants). Foot ulcers in people with diabetes It is uncertain whether there is a difference in time to complete healing between hyaluronic acid and lyophilised collagen because the certainty of evidence is very low (MD 16.60, 95% CI 7.95 to 25.25; 1 study, 20 participants). It is uncertain whether there is a difference in complete ulcer healing (RR 2.20, 95% CI 0.97 to 4.97; 1 study, 34 participants) or change in ulcer size (MD -0.80, 95% CI -3.58 to 1.98; 1 study, 25 participants) between hyaluronic acid and conventional dressings because the certainty of evidence is very low. Leg ulcers We are uncertain whether there is a difference in complete wound healing (RR 0.98, 95% CI 0.26 to 3.76), percentage of adverse events (RR 0.79, 95% CI 0.22 to 2.80), pain (MD 2.10, 95% CI -5.81 to 10.01), or change in ulcer size (RR 2.11, 95% CI 0.92 to 4.82) between hyaluronic acid + hydrocolloid and hydrocolloid because the certainty of evidence is very low (1 study, 125 participants). It is uncertain whether there is a difference in change in ulcer size between hyaluronic acid and hydrocolloid because the certainty of evidence is very low (RR 1.02, 95% CI 0.84 to 1.25; 1 study, 143 participants). We are uncertain whether there is a difference in complete wound healing between hyaluronic acid and paraffin gauze because the certainty of evidence is very low (RR 2.00, 95% CI 0.21 to 19.23; 1 study, 24 ulcers from 17 participants). When compared with neutral vehicle, hyaluronic acid probably improves complete ulcer healing (RR 2.11, 95% CI 1.46 to 3.07; 4 studies, 526 participants; moderate-certainty evidence); may slightly increase the reduction in pain from baseline (MD -8.55, 95% CI -14.77 to -2.34; 3 studies, 337 participants); and may slightly increase change in ulcer size, measured as mean reduction from baseline to 45 days (MD 30.44%, 95% CI 15.57 to 45.31; 2 studies, 190 participants). It is uncertain if hyaluronic acid alters incidence of infection when compared with neutral vehicle (RR 0.89, 95% CI 0.53 to 1.49; 3 studies, 425 participants). We are uncertain whether there is a difference in change in ulcer size (cm²) between hyaluronic acid and dextranomer because the certainty of evidence is very low (MD 5.80, 95% CI -10.0 to 21.60; 1 study, 50 participants). We downgraded the certainty of evidence due to risk of bias or imprecision, or both, for all of the above comparisons. No trial reported health-related quality of life or wound recurrence. Measurement of change in ulcer size was not homogeneous among studies, and missing data precluded further analysis for some comparisons.

There is currently insufficient evidence to determine the effectiveness of hyaluronic acid dressings in the healing of pressure ulcers or foot ulcers in people with diabetes. We found evidence that hyaluronic acid probably improves complete ulcer healing and may slightly decrease pain and increase change in ulcer size when compared with neutral vehicle. Future research into the effects of hyaluronic acid in the healing of chronic wounds should consider higher sample size and blinding to minimise bias and improve the quality of evidence.