The Histological Basis of Maggot Therapy: A Narrative Review

Abstract

Maggot debridement therapy (MDT) is a biological treatment approach using sterile Lucilia sericata larvae in chronic and necrotic wounds. Initially defined as a selective debridement method, MDT is now known to exhibit multifaceted biological effects that regulate the wound microenvironment at the cellular and molecular levels. The aim of this review is to evaluate the histological basis of MDT in wound healing in light of current literature. This includes addressing the biological effects of necrotic tissue removal, inflammation regulation, granulation tissue formation, fibroblast activation, extracellular matrix remodeling, angiogenesis, macrophage polarization, and larval excretion/secretion products. Current studies show that proteolytic enzymes, antimicrobial peptides, and low molecular weight bioactive metabolites found in larval secretions not only facilitate debridement but also support biofilm control, immunomodulation, cell migration, and tissue remodeling. However, a significant portion of the current clinical evidence is based on experimental studies and clinical trials with limited sample sizes. In conclusion, MDT, when applied in conjunction with appropriate patient selection and multidisciplinary wound care, is a promising approach that can guide the chronic wound microenvironment towards a proliferative healing phase, support histological repair, and lay the groundwork for novel molecular-based biological therapies.

Keywords

• Maggot Therapy
• Lucilia Sericata
• Granulation Tissue
• Fibroblast
• Angiogenesis

Maggot Terapinin Histolojik Temelleri: Güncel Bir Derleme

Abstract

Maggot debritman tedavisi (MDT), steril Lucilia sericata larvalarının kronik ve nekrotik yaralarda kullanıldığı biyolojik bir tedavi yaklaşımıdır. Başlangıçta seçici debridman yöntemi olarak tanımlanan MDT'nin günümüzde yara mikroçevresini hücresel ve moleküler düzeyde düzenleyen çok yönlü biyolojik etkiler gösterdiği bilinmektedir. Bu derlemenin amacı, MDT'nin yara iyileşmesindeki histolojik temellerini güncel literatür ışığında değerlendirmektir. Bu kapsamda nekrotik dokunun uzaklaştırılması, inflamasyonun düzenlenmesi, granülasyon dokusu oluşumu, fibroblast aktivasyonu, ekstraselüler matriks yeniden yapılanması, anjiyogenez, makrofaj polarizasyonu ve larval ekskresyon/sekresyon ürünlerinin biyolojik etkileri ele alınmıştır. Güncel çalışmalar, larval sekresyonlarda bulunan proteolitik enzimler, antimikrobiyal peptidler ve düşük molekül ağırlıklı biyoaktif metabolitlerin yalnızca debridmanı kolaylaştırmadığını; biyofilm kontrolü, immünomodülasyon, hücre göçü ve doku yeniden yapılanmasını da desteklediğini göstermektedir. Bununla birlikte mevcut klinik kanıtların önemli bölümü deneysel çalışmalar ve sınırlı örneklemli klinik araştırmalara dayanmaktadır. Sonuç olarak MDT, uygun hasta seçimi ve multidisipliner yara bakımıyla birlikte uygulandığında kronik yara mikroçevresini proliferatif iyileşme fazına yönlendirebilen, histolojik onarımı destekleyen ve moleküler temelli yeni biyolojik tedavilere zemin oluşturabilecek umut verici bir yaklaşımdır.

Keywords

• Maggot Terapi
• Lucilia Sericata
• Granülasyon Dokusu
• Fibroblast
• Anjiyogenez

References

1. 1. Diller RB, Tabor AJ. (2022). The role of the extracellular matrix in wound healing: A review. Biomimetics. 7(3):87. doi:10.3390/biomimetics7030087.
2. 2. Cialdai F, Risaliti C, Monici M. (2022). Role of fibroblasts in wound healing and tissue remodeling on Earth and in space. Frontiers in Bioengineering and Biotechnology. 10:958381. doi:10.3389/fbioe.2022.958381.
3. 3. Sig AK, Koru O, Araz E. (2018). Maggot debridement therapy: Utility in chronic wounds and a perspective beyond. Wound Practice and Research.26(3):114-121.
4. 4. Naik G, Harding KG. (2017). Maggot debridement therapy: The current perspectives. Chronic Wound Care Management and Research.4:121–128. doi:10.2147/CWCMR.S117271.
5. 5. Jordan A, Khiyani N, Bowers SR, Lukaszczyk JJ, Stawicki SP. (2018). Maggot debridement therapy: A practical review. International Journal of Academic Medicine.4(1):21–34. doi:10.4103/IJAM.IJAM_6_18.
6. 6. Nigam Y, Morgan C. ( 2016). Does maggot therapy promote wound healing? The clinical and cellular evidence. Journal of the European Academy of Dermatology and Venereology. 30(5):776–782.doi:10.1111/jdv.13534.
7. 7. Lin C, Lin CW, Wu SH, Cheng H. (2025). Effectiveness of Maggot Debridement Therapy for Chronic Wounds: A Systematic Review and Meta‐Analysis of Randomised Controlled Trials. Wound Repair and Regeneration.33. doi:10.1111/wrr.70095.
8. 8. Tombulturk FK, Kanigur-Sultuybek G. (2021). A molecular approach to maggot debridement therapy with Lucilia sericata and its excretions/secretions in wound healing. Wound Repair and Regeneration. 29(6):1051–1061. doi:10.1111/wrr.12961.

9. 9. Bazaliński D, Kózka M, Karnas M, Więch P. (2019). Effectiveness of chronic wound debridement with the use of larvae of Lucilia sericata. Journal of Clinical Medicine. 8(11):1845. doi:10.3390/jcm8111845.
10. 10. Gazi U, Taylan-Ozkan A, Mumcuoglu KY. (2021). The effect of Lucilia sericata larval excretion/secretion (ES) products on cellular responses in wound healing. Med Vet Entomol. 35(3):257-266. doi:10.1111/mve.12497
11. 11. Akbaş F, Özaydın A, Polat E, Onaran İ. (2020). Lucilia sericata larval secretions stimulating wound healing effects on rat dermal fibroblast cells. Records of Natural Products. 14(5):340–354. doi:10.25135/rnp.180.20.03.1582.
12. 12. Sun X, Chen J, Zhang J, Wang W, Sun J, Wang A. (2016). Maggot debridement therapy promotes diabetic foot wound healing by up-regulating endothelial cell activity. Journal of Diabetes and its Complications. 30(2):318–322. doi:10.1016/j.jdiacomp.2015.11.009.
13. 13. Bexfield A, Bond AE, Morgan C, Wagstaff J, Newton RP, Ratcliffe NA, et al. (2010). Amino acid derivatives from Lucilia sericata excretions/secretions may contribute to the beneficial effects of maggot therapy via increased angiogenesis. British Journal of Dermatology. 162(3):554–562.doi:10.1111/j.1365-2133.2009.09530.x.
14. 14. Mohd Zubir MZ, Holloway S, Mohd Noor N. (2020). Maggot therapy in wound healing: A systematic review. International Journal of Environmental Research and Public Health. 17(17):6103. doi:10.3390/ijerph17176103.
15. 15. Dauros Singorenko P, Rosario R, Windsor J, Phillips A, Blenkiron C. (2017). The transcriptional responses of cultured wound cells to the excretions and secretions of medicinal Lucilia sericata larvae. Wound Repair and Regeneration. 25(1):119–129. doi:10.1111/wrr.12499.
16. 16. Franta Z, Vogel H, Lehmann R, Rupp O, Goesmann A, Vilcinskas A. (2016). Next Generation Sequencing Identifies Five Major Classes of Potentially Therapeutic Enzymes Secreted by Lucilia sericata Medical Maggots. BioMed Res Int. 2016:8285428. doi:10.1155/2016/8285428
17. 17. Wilson MR, Nigam Y, Jung W, Knight J, Pritchard DI. (2016). The impacts of larval density and protease inhibition on feeding in medicinal larvae of the greenbottle fly Lucilia sericata. Med Vet Entomol. 30(1):1-7. doi:10.1111/mve.12138
18. 18. Pritchard, D.I., Čeřovský, V., Nigam, Y., Pickles, S.F., Cazander, G., Nibbering, P.H., (2016). Bültemann, A. and Jung, W. TIME management by medicinal larvae. Int Wound J, 13: 475-484. https://doi.org/10.1111/iwj.12457
19. 19. Cytryńska M, Rahnamaeian M, Zdybicka-Barabas A, Dobslaff K, Züchner T, Sacheau G, Innis CA and Vilcinskas A. (2020). Proline-Rich Antimicrobial Peptides in Medicinal Maggots of Lucilia sericata Interact With Bacterial DnaK But Do Not Inhibit Protein Synthesis. Front. Pharmacol. 11:532. doi: 10.3389/fphar.2020.00532
20. 20. Bazaliński, D.; Przybek-Mita, J.; Lisowicz, K.; Skórka, M.; Więch, P. (2023). Defensins of Lucilia sericata Larvae and Their Influence on Wound Repair Processes in Practical Assessment—A Study of Three Cases. Int. J. Environ. Res. Public Health 20, 5357. https://doi.org/10.3390/ijerph20075357
21. 21. Morris D, Flores M, Harris L, Gammon J, Nigam Y. (2023). Larval Therapy and Larval Excretions/Secretions: A Potential Treatment for Biofilm in Chronic Wounds? A Systematic Review. Microorganisms. 11(2):457. https://doi.org/10.3390/microorganisms11020457
22. 22. Tamura T, Cazander G, Rooijakkers SHM, Trouw LA, Nibbering PH. (2017). Excretions/secretions from medicinal larvae (Lucilia sericata) inhibit complement activation by two mechanisms. Wound Rep Reg. 25(1):41-50. doi:10.1111/wrr.12504
23. 23. Potekaev NN, Borzykh OB, Medvedev GV, Pushkin DV, Petrova MM, Petrov AV, et al. (2021). The role of extracellular matrix in skin wound healing. Journal of Clinical Medicine. 10(24):5947. doi:10.3390/jcm10245947.
24. 24. Wang TY, Wang W, Li FF, Chen YC, Jiang D, Chen YD, et al. (2020). Maggot excretions/secretions promote diabetic wound angiogenesis via miR18a/19a–TSP-1 axis. Diabetes Research and Clinical Practice. 165:108140. doi:10.1016/j.diabres.2020.108140.
25. 25. Čeřovský V, Bém R. (2014). Lucifensins, the insect defensins of biomedical importance: The story behind maggot therapy. Pharmaceuticals. 7(3):251–264. doi:10.3390/ph7030251.
26. 26. Szczepanowski Z, Grabarek B, Boroń D, Tukiendorf A, Kulik-Parobczy I, Miszczyk L. (2022). Microbiological effects in patients with leg ulcers and diabetic foot treated with Lucilia sericata larvae. International Wound Journal. 19(1):135–143. doi:10.1111/iwj.13605.
27. 27. Nigam Y, Wilson MR. Maggot-assisted wound healing. (2022). In: A Complete Guide to Maggot Therapy. Open Book Publishers; doi:10.11647/OBP.0300.10.
28. 28. Sun XJ, Jiang D, Chen YD, Wang W, Wang TY, Wang AP. (2024). Maggot debridement therapy stimulates wound healing by altering macrophage activation. International Wound Journal. 21(2):e14477. doi:10.1111/iwj.14477.
29. 29. Linger RJ, Belikoff EJ, Yan Y, Li F, Wantuch HA, Fitzsimons HL, et al. (2016). Towards next generation maggot debridement therapy: Transgenic Lucilia sericata larvae that produce and secrete a human growth factor. BMC Biotechnology. 16:30. doi:10.1186/s12896-016-0263-z.