By Ron Sherman MD, MSC, DTM&H

Over 80 years ago, Dr. William Baer — then Chair of Orthopedic Surgery at Johns Hopkins — observed that wounds debrided with maggot therapy healed at least as well and as fast as any surgically debrided wound; but wounds that continued to receive maggot therapy beyond the point of debridement would heal even faster than normal. What evidence of that do we have today?

These days, most everyone acknowledges that medicinal maggots do an excellent job at debridement. Their digestive enzymes dissolve infected, necrotic tissue safely and efficiently. But there is not widespread agreement about their ability to promote wound healing. In my personal experience speaking with therapists about maggot-induced wound healing, most therapists who use maggot therapy reply “Of course they stimulate healing, I see it all the time;” most therapists inexperienced with maggot therapy say “That’s ridiculous, show me the data” and most non-therapists simply drop their jaw and say: “Wow! How can that be? Why would that be?”

This week I am in Houston, at the National Pressure Ulcer Advisory Panel’s (NPUAP) biennial conference, where I am presenting a poster on this very issue. Along with Katherine Watt, BS, BTER Foundation Research Intern, we are reviewing the literature on maggot-induced wound healing. Our work is ongoing, but let me briefly share our results to date.

After searching PubMed and the BTER Foundation Library archives for peer-reviewed maggot therapy articles published over the past 20 years (of which we identified 252!), we then hand-selected those articles which provided original evidence supporting or refuting the hypothesis that maggot therapy speeds wound healing or alters physiology in a way that likely would speed wound healing. In this way, a total of 27 original research articles were identified as relevant to the issue of maggot-induced wound healing. All but two of these studies supported the notion by demonstrating clinical measurements of hastened wound healing or else identifying specific mechanisms of action, such as increased cellular mitosis, hastened migration of fibroblasts over the wound bed, modulation of cytokines, angiogenesis, increased local perfusion, or biofilm degradation and inhibition.

Seven controlled clinical studies suggested or demonstrated faster rates of healing in the maggot therapy group, but they did not follow patients until wound closure (they were designed primarily as debridement studies).

Two clinical trials of maggot therapy demonstrated debridement to be significantly faster in the maggot therapy groups, but did not demonstrate faster wound closure. Dumville et al (2009) debrided venous stasis ulcers with either “free range maggots” (which directly and freely contact the wound base), contained maggots (“biobags” which separate the maggots within a polyester net bag), or hydrogel (control group). Wounds were followed until completely healed; but maggot therapy was provided only during debridement (average of 2 weeks). Opletalova et al (2012) debrided wounds with contained maggots (within a polyvinyl alcohol [PVA] bag) vs. surgery, but followed subjects only for 15 days (not to wound closure). Why did these two clinical studies show no enhanced wound healing with maggot therapy, unlike the other studies? Did they fail to demonstrate a healing effect because there really is none? Did they fail to demonstrate a healing effect because these two studies used bagged maggots, with or without free-range maggots (Steenvoorde et al, 2005), unlike all of the studies which demonstrated a healing effect, using free-range maggots?

I choose to interpret them in a more positive light, because they both are consistent with Dr. Baer’s earlier observations: they demonstrated that maggot debridement was effective and efficient, and was followed by normal (not accelerated) healing. They do not exclude the fact that maggots applied after debridement might have hastened wound closure, and therefore they are not really in conflict with William Baer and all of the other modern studies that demonstrated growth-promoting actions of medicinal maggots and their secretions.

Where do we go from here? We have not seen a single prospective clinical trial proving or disproving a maggot-associated wound healing effect. We still need a clinical trial of maggot therapy on clean but non-healing wounds, with follow-up continuing through wound closure.

What do you think? Will you join us in this effort?

Sources
Armstrong DG et al. 2005. Maggot therapy in "lower-extremity hospice" wound care: fewer amputations and more antibiotic-free days. J. Am. Podiatr. Med. Assoc. 95:254-7
Bexfield A et al. 2010. Amino acid derivatives from Lucilia sericata excretions/secretions may contribute to the beneficial effects of maggot therapy via increased angiogenesis. Br. J. Dermatol. 162:554-62
Cazander G, Schreurs MW, Renwarin L, Dorresteijn C, Hamann D, Jukema GN. 2012. Maggot excretions affect the human complement system. Wound Repair Regen. 20:879-86
Cazander G, van Veen KE, Bouwman LH, Bernards AT, Jukema GN. 2009. The influence of maggot excretions on PAO1 biofilm formation on different biomaterials. Clin. Orthop. Relat Res. 467:536-454.
Dumville JC et al. 2009. Larval therapy for leg ulcers (VenUS II): randomised controlled trial BMJ 338:b773
Honda K et al. 2011. A novel mechanism in maggot debridement therapy: protease in excretion/secretion promotes hepatocyte growth factor production. Am. J. Physiol Cell Physio.l 301:C1423-C1430
Horobin AJ et al. Promotion of human dermal fibroblast migration, matrix remodelling and modification of fibroblast morphology within a novel 3D model by Lucilia sericata larval secretions. J Invest Dermatol. 2006;126:1410-8
Horobin AJ et al. Maggots and wound healing: an investigation of the effects of secretions from Lucilia sericata larvae upon the migration of human dermal fibroblasts over a fibronectin-coated surface. Wound Repair Regen. 2005; 13:422-33
Horobin AJ et al. 2003. Maggots and wound healing: an investigation of the effects of secretions from Lucilia sericata larvae upon interactions between human dermal fibroblasts and extracellular matrix components. Br. J. Dermatol. 148:923-33
Markevich YO et al. Maggot therapy for diabetic neuropathic foot wounds: a randomized study. Eur Assoc Study Diabetes, 17-21, September, 2000; Jerusalem, Israel: 2000. (Abstract)
Mumcuoglu KY et al. 1997. [Maggot therapy for gangrene and osteomyelitis] Harefuah 132:323-5, 382
Pecivova J et al. 2008. Effect of the extract from salivary glands of Lucilia sericata on human neutrophils. Neuro. Endocrinol. Lett. 29:794-7
Picazo M et al. 2005. [Sterile maggots as adjuvant procedure for local treatment in a patient with proximal calciphylaxis] Nefrologia. 25:559-62
Opletalova et al. 2012. Maggot Therapy for Wound Debridement. Arch Dermatol. 148: 432-8
Prete PE. 1997. Growth effects of Phaenicia sericata larval extracts on fibroblasts: mechanism for wound healing by maggot therapy Life Sci. 60:505-10
Sealby N. 2004. The use of maggot therapy in the treatment of a malignant foot wound. Br. J. Community Nurs. 9:S16-S19
Sherman RA et al. 1995. Maggot therapy for treating pressure ulcers in spinal cord injury patients J. Spinal Cord. Med. 18:71-4
Sherman RA. 2002a. Maggot therapy for foot and leg wounds. Int. J. Low Extrem. Wounds. 1:135-42
Sherman RA. 2002b. Maggot versus conservative debridement therapy for the treatment of pressure ulcers. Wound. Repair Regen. 10:208-14
Sherman RA. 2003. Maggot therapy for treating diabetic foot ulcers unresponsive to conventional therapy. Diabetes Care. 26:446-51
Sherman RA et al. Maggot therapy for problematic wounds: uncommon and off-label applications. Adv. Skin Wound. Care. 20:602-10
Steenvoorde P et al. 2005. Maggot debridement therapy: free-range or contained? An in-vivo study. Adv. Skin Wound Care. 18:430-5
Steenvoorde P et al. 2007. Maggot debridement therapy in the palliative setting. Am. J. Hosp. Palliat. Care. 24:308-10
Tanyuksel M et al. 2005. Maggot debridement therapy in the treatment of chronic wounds in a military hospital setup in Turkey. Dermatology. 210:115-8
Wang SY et al. 2010. Clinical research on the bio-debridement effect of maggot therapy for treatment of chronically infected lesions. Orthop. Surg. 2:201-6
Wollina U et al. 2002. Biosurgery supports granulation and debridement in chronic wounds--clinical data and remittance spectroscopy measurement. Int. J. Dermatol. 41:635-9
Zhang Z et al. Fatty acid extracts from Lucilia sericata larvae promote murine cutaneous wound healing by angiogenic activity. Lipids Health Dis. 2010; 9:24
Zhang Z et al. 2010. A new effective scaffold to facilitate peripheral nerve regeneration: chitosan tube coated with maggot homogenate product. Med. Hypotheses. 74:12-4

About The Author
Ron Sherman MD, MSC, DTM&H has led a long career at the forefront of biotherapy, pioneering the development of medicinal maggots for over 25 years. He is now retired from his faculty position at the University of California, but continues to volunteer as Director and Board Chair of the BTER Foundation, and as Laboratory Director of Monarch Labs.

The views and opinions expressed in this blog are solely those of the author, and do not represent the views of WoundSource, Kestrel Health Information, Inc., its affiliates, or subsidiary companies.

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