Gwendolyn Cazander

Complement Activation and Inhibition in Wound Healing

Complement activation is needed to restore tissue injury; however, inappropriate activation of complement, as seen in chronic wounds can cause cell death and enhance inflammation, thus contributing to further injury and impaired wound healing. Therefore, attenuation of complement activation by specific inhibitors is considered as an innovative wound care strategy. Currently, the effects of several complement inhibitors, for example, the C3 inhibitor compstatin and several C1 and C5 inhibitors, are under investigation in patients with complement-mediated diseases. Although (pre)clinical research into the effects of these complement inhibitors on wound healing is limited, available data indicate that reduction of complement activation can improve wound healing. Moreover, medicine may take advantage of safe and effective agents that are produced by various microorganisms, symbionts, for example, medicinal maggots, and plants to attenuate complement activation. To conclude, for the development of new wound care strategies, (pre)clinical studies into the roles of complement and the effects of application of complement inhibitors in wound healing are required.

Multiple actions of Lucilia sericata larvae in hard‐to‐heal wounds

In Europe ≈15,000 patients receive larval therapy for wound treatment annually. Over the past few years, clinical studies have demonstrated the success of larvae of Lucilia sericata as debridement agents. This is based on a combination of physical and biochemical actions. Laboratory investigations have advanced our understanding of the biochemical mechanisms underlying the beneficial effects of larval secretions, including removal of dead tissue, reduction of the bacterial burden, and promotion of tissue regeneration. The present article summarizes our current understanding of the microbiological, immunological, and wound healing actions of larval therapy, and the molecules involved in these beneficial effects. Future studies will focus on the isolation, identification, and (pre)clinical testing of the effective molecules of L. sericata larvae. These molecules may be candidates for the development of new agents for the treatment of several infectious and inflammatory diseases, including chronic wounds.

Multiple actions of Lucilia sericata larvae in hard-to-heal wounds Larval secretions contain molecules that accelerate wound healing, reduce chronic inflammation and inhibit bacterial infection

In Europe ≈15,000 patients receive larval therapy for wound treatment annually. Over the past few years, clinical studies have demonstrated the success of larvae of Lucilia sericata as debridement agents. This is based on a combination of physical and biochemical actions. Laboratory investigations have advanced our understanding of the biochemical mechanisms underlying the beneficial effects of larval secretions, including removal of dead tissue, reduction of the bacterial burden, and promotion of tissue regeneration. The present article summarizes our current understanding of the microbiological, immunological, and wound healing actions of larval therapy, and the molecules involved in these beneficial effects. Future studies will focus on the isolation, identification, and (pre)clinical testing of the effective molecules of L. sericata larvae. These molecules may be candidates for the development of new agents for the treatment of several infectious and inflammatory diseases, including chronic wounds.

Synergism between maggot excretions and antibiotics

Maggots are successfully used to treat severe, infected wounds. This study investigated whether maggot excretions/secretions influence the antibacterial activity of different antibiotics. Minimal inhibitory concentrations and minimal bactericidal concentrations (MBC) were determined of gentamicin and flucloxacillin for Staphylococcus aureus, of penicillin for Streptococcus pyogenes, of amoxicillin and vancomycin for Enterococcus faecalis, of gentamicin for Enterobacter cloacae, and of gentamicin, tobramycin, and ciprofloxacin for Pseudomonas aeruginosa by checkerboard titration. A range of concentrations of antibiotics in combination with excretions/secretions was examined to investigate the potential of maggot excretions/secretions to affect antibacterial activity. The results showed a dose‐dependent increase of the antibacterial effect of gentamicin in the presence of excretions/secretions on S. aureus. Minimal concentrations and MBC of gentamicin decreased, respectively, 64‐ and 32‐fold. The MBC of flucloxacillin and excretions/secretions against S. aureus were also decreased. The other antibiotic and excretions/secretions combinations exerted an indifferent effect. Excretions/secretions alone did not have any antibacterial effect. The synergism between gentamicin and maggot excretions/secretions could be of direct importance in clinical practice, because it could allow the use of lower doses of gentamicin and thus minimize the risk of gentamicin‐related side effects.

TIME management by medicinal larvae

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.