TIME management by medicinal larvae

Abstract

Wound bed preparation (WBP) is an integral part of the care programme for chronic wounds. The acronym TIME is used in the context of WBP and describes four barriers to healing in chronic wounds; namely, dead Tissue, Infection and inflammation, Moisture imbalance and a non-migrating Edge. Larval debridement therapy (LDT) stems from observations that larvae of the blowfly Lucilia sericata clean wounds of debris. Subsequent clinical studies have proven debriding efficacy, which is likely to occur as a result of enzymatically active alimentary products released by the insect. The antimicrobial, anti-inflammatory and wound healing activities of LDT have also been investigated, predominantly in a pre-clinical context. This review summarises the findings of investigations into the molecular mechanisms of LDT and places these in context with the clinical concept of WBP and TIME. It is clear from these findings that biotherapy with L. sericata conforms with TIME, through the enzymatic removal of dead tissue and its associated biofilm, coupled with the secretion of defined antimicrobial peptides. This biotherapeutic impact on the wound serves to reduce inflammation, with an associated capacity for an indirect effect on moisture imbalance. Furthermore, larval serine proteinases have the capacity to alter fibroblast behaviour in a manner conducive to the formation of granulation tissue.

Excretions/secretions from medicinal larvae (Lucilia sericata) inhibit complement activation by two mechanisms

“…As larval ES contain many kinds of proteases, we hypothesized that complement inactivation was due to degradation of the complement proteins by ES. All proteins associated with complement activation, including C3, C4, C2, C1q, MBL, factor B, C5a, C3a, C3b, and C5 were degraded by ES (Figure A; data for C3a, C3b, and C5 are not shown).…”

“…Wound healing is a dynamic and complex process that can be explained by a three‐stage strategy comprising of an inflammatory, proliferative, and remodeling phase . Although a wound can be chronic when any of these phases is impaired, excessive inflammation is the most important to be addressed.…”

“…Chronic, non‐healing wounds are often characterized by the presence of bacterial biofilms, slough, and cell debris in the wound bed . The impaired wound healing is often a result of an inappropriate inflammatory process and/or deleterious composition of wound fluid.…”

Quality control of a medicinal larval (Lucilia sericata) debridement device based on released gelatinase activity

“…The efficacy of larval debridement therapy against a variety of chronic wounds has been reported in clinical trials and anecdotal observations, particularly in relation to the rate and extent of debridement in comparison with those afforded by standard treatments (Gottrup & Jørgensen, ; Mudge et al ., ), as well as in relation to a reduction in the risk for requirement for major amputation (Sherman, ; Waniczek et al ., ). It is acknowledged that the degradation of non‐viable tissue is enzymatically driven, assisted by antimicrobials for the removal of associated bioburden, and that use of these insect‐derived products leads to the apparent promotion of healing (Sherman, ; Pritchard et al ., ). Contained larval debridement devices, such as the porous BioBag, permit the passage of enzymatically active larval alimentary products (LAP) from within the polyester pouch to the wound environment.…”

What is the optimal treatment time for larval therapy? A study on incubation time and tissue debridement by bagged maggots of the greenbottle fly, Lucilia sericata

“…Being necrophagous by nature, the larvae break down and consume necrotic tissue enzymatically by a process of extracorporeal digestion. This is achieved by the release of excretions/secretions containing a mixture of proteolytic, glycolytic, lipolytic, and nuclease enzymes onto the tissue surface, causing liquefaction and digestion of the necrotic tissue, which is subsequently ingested . However, as effective as this feeding mechanism may be, the larvae cannot feed indefinitely.…”