Efficacy of Combined Bromelain and Hyaluronic Acid as an Enzymatic Debridement Agent for Full-Thickness Burn Wounds in Wistar Rats (Rattus norvegicus)

Abstract

ABSTRACT:

Background: Retained eschar delays healing of full-thickness burns, and the wound bed exposed by enzymatic debridement is vulnerable to desiccation. This study evaluated the effect of topical 10% bromelain, alone and combined with hyaluronic acid (HA), on burn wound healing in rats.

Methods: Twenty-four male Wistar rats with standardized 2 × 1 cm full-thickness dorsal burns were randomized into six groups receiving hydrogel control, 10% bromelain, or bromelain plus HA once daily, with endpoints on day 3 or day 7 (n = 4 per group). Epithelialized area was quantified by digital planimetry, neo-epidermal height by hematoxylin and eosin staining, and dermal collagen density by Masson trichrome with ImageJ. Kruskal-Wallis, Mann-Whitney, and Spearman tests were applied.

Results: Twenty-three rats completed the study. Day 7 epithelialized area reached 1.16 ± 0.39 cm² with bromelain and 1.07 ± 0.52 cm² with the combination versus 0.88 ± 0.39 cm² in controls. Neo-epidermal height was 3.4-fold greater with bromelain plus HA (232.99 ± 139.10 µm) than with bromelain alone (68.39 ± 136.77 µm), and three of four bromelain-only wounds showed no measurable epithelium. Day 7 collagen density was 40.50 ± 9.05% with the combination versus 32.39 ± 3.76% with bromelain alone, and bromelain produced the highest day 3 collagen density (44.92 ± 11.57%). Differences were not statistically significant (Kruskal-Wallis p = 0.145 to 0.323, Mann-Whitney p = 0.139 to 0.773).

Conclusion: Adding HA after bromelain debridement was consistently associated with thicker re-epithelialization and preserved dermal collagen, supporting integrated enzymatic debridement with moisture-retentive wound bed care.