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.

Keywords: Chronic wound; Infection; Larval debridement therapy; TIME; Tissue regeneration.

Figure 1

An 81‐year‐old male patient with a venous leg ulcer, which had been in existence for several years, was hospitalised after thrombosis and arterial lung embolism. Co‐morbidities included hypertension, hyperlipoproteinaemia and obesity. The patient was treated with larval therapy: two cycles with one BioBag^® 200 for 2 days and two BioBag^® 100 for 4 days. Co‐treatments included lymph drainage, compression and anticoagulant therapy (Marcumar). (a) Sloughy venous leg ulcer before the onset of larval debridement therapy (LDT). (b) Compression therapy was applied while BioBags^® (showing 3 of 4) were used. The foam surrounding the wound protects the larvae from compression. (c) After two treatment cycles of LDT (one BioBag^® 200 for 2 days and two BioBag^® 100 for 4 days), the wound bed was fully granulated and prepared for further healing.

Figure 2

Protein sequences of two predominant maggot debridement enzymes. The catalytic triad forming the active sites of each enzyme (serine proteinases) is illustrated by bold underline (HDS). Each of these resilient enzymes is capable of digesting the slough proteins from chronic wounds. Serine proteinases also have an antimicrobial function and promote fibroblast motogenesis. They have a multifactorial impact on the wound ecosystem.

Figure 3

The amino acid sequence of lucifensin (Lucilia sericata defensin), its tertiary structure and its effect on bacterial cell walls. Electron micrographs of negatively stained Bacillus subtilis either untreated (A) or treated by lucifensin for 60 minutes (B). Scale bars represent 1 µm. Illustrated representation of the three‐dimensional structure of lucifensin (PDB ID: 2LLD) generated by Pymol (http://www.pymol.org).