Effect of Bromelain-Based Enzymatic Debridement on Skin Cells

Abstract

Several reports have concluded that enzymatic debridement based on Bromelain (NX) is selective and efficient. Although clinical trials showed that viable tissue is not damaged at the macroscopic level, the effect on the cellular level is largely unknown. The current study is meant to close this gap by evaluating whether NX has an effect on vital cells of the human dermis on a cellular level. In an experimental in vitro study design, the effect of NX on human keratinocytes, fibroblasts, and macrophages was analyzed. Enzymatic treatment was performed for 4 hours by using either cell culture medium or phosphate-buffered saline as diluting agent for NX. Cell viability and relative cell number in relation to untreated control cells were determined using a resazurin-based assay. In addition, the development of enzyme activity during clinical treatment was analyzed: wound fluid collected from a burn wound at different points of debridement was applied on collagen-elastin disks to prove enzymatic digestion activity. Both keratinocytes and fibroblasts were damaged by NX even at low concentrations. Both cell types showed improved survival when a medium was used for dissolving NX. Macrophages appeared to resist NX treatment more efficiently than the other cell types. In the clinical trial, NX activity in the wound fluid decreased clearly following 4 hours of enzymatic debridement. NX induces toxicity of vital skin cells in vitro. However, macrophages appear to be more resistant against NX treatment in vitro. The inflammatory responses of vital cells in the burn wound itself are likely to inhibit NX activity. The effect of this inflammatory process on NX activity will have to be investigated in future studies.

In vitro performance of free and encapsulated bromelain

“…Still, other studies have shown that different preparations of bromelain could induce cell cycle arresting in G0 phase (quiescence), which would explain the inhibition of cell proliferation 39 . These results reinforce the understanding that the healing effect of bromelain in wound care is mainly due to its debriding action, which removes cell debris and necrotic tissues in vivo, in accordance with other studies 6 , 38 , 40 , 41 .…”

“…Thus, the proteolytic action of bromelain could be affecting cells more directly than in the condition of cultivation with medium supplemented with 5% FBS. A similar effect was reported by Schulz et al 38 when comparing the effect of a formulation containing bromelain on the viability of human fibroblasts and keratinocytes (primary cultures) in complete culture medium or in phosphate-buffered saline (PBS). The replacement of culture medium with PBS intensified the cytotoxic effect of bromelain on both cells evaluated.…”

Beneficial Properties of Bromelain

“…[186]. It is worth noting that Schulz et al [187] and Berner et al [188] pay attention to the low selectivity of the bromelain-based enzymatic debridement (NexoBrid ® ), which has a toxic effect on viable human skin cells, especially at high concentrations.…”

Role, Development, and Value of Enzymatic Debridement as Integral Component in Initial Treatment of Burn Injuries Exemplified by NexoBrid®

“…The early removal of necrotic eschar represents the standard in modern burn therapy in order to reduce or prevent local infection, sepsis, scarring, or other complications and allow proper wound bed evaluation. Enzymatic debridement offers a needs-based technique with a maximum of healthy tissue conservation by providing a selective and sparing concept for necrotic tissue ablation [25][26][27]. The application of plant-based agents such as resin, honey, or other herbal remedies on burn wounds was already described in ancient Egypt (1600 BC) [28].…”