Investigating the therapeutic potential of medical leech and leech saliva extract in flap survival: an in vivo study using rats
Ünal K, Emre Erol M, Dayanır D, Deniz E, Ayhan H, Fındıkçıoğlu K (2025) · Journal of Complementary & Integrative Medicine · n=0
Study Profile
- Design
- controlled animal experiment with three groups of female Wistar albino rats subjected to a dorsal random skin flap model (Gazi University Faculty of Medicine, Ankara, Turkey)
- Sample size (n)
- 0
- Intervention
- Three groups: control (flap only), medicinal leech therapy (MLT) group, and leech saliva extract (LSE) injection group; histological, immunohistochemical (VEGF), and ELISA-based biochemical analyses performed at postoperative day 7
- Comparator
- Sham/control group (flap only without leech intervention)
- Primary endpoint
- Flap necrosis area, VEGF-positive cell percentage, neovascularization, epithelial regeneration, granulation tissue thickness, and inflammatory cell infiltration on postoperative day 7
- Primary result
- Flap necrosis area was significantly lower in both MLT and LSE groups versus control (p<0.05); VEGF-positive cells, neovascularization, epithelial regeneration, and granulation tissue thickness all significantly higher in MLT and LSE groups versus control (p<0.05); inflammatory cells substantially lower in LSE group versus control (p<0.05); first study to demonstrate the effect of medicinal leech extract injection in a flap model
- Follow-up duration
- 7 postoperative days
- PMID
- 40968464
Key Findings
- First in vivo rat study to investigate medicinal leech saliva extract injection in a dorsal random flap model
- Both medicinal leech therapy (MLT) and leech saliva extract (LSE) injection significantly reduced flap necrosis area
- VEGF-positive cells, neovascularization, epithelial regeneration, and granulation tissue thickness were all enhanced in both leech groups
- Leech saliva extract injection significantly reduced inflammatory cell infiltration
- Provides molecular and histological mechanistic support for the clinical use of leech therapy in flap salvage
Limitations
- Animal model (rat dorsal random flap) - direct human translation requires further study
- Short follow-up (7 postoperative days) - long-term outcomes untested
- Small sample size per arm (not specified per group in abstract)
- Saliva extract concentration and standardization details unclear
- Mechanism characterization limited to selected markers (VEGF, histology)
Clinical Implications
Ünal 2025 is a Turkish preclinical animal study that documents both whole-leech therapy and leech saliva extract injection produce significant histological and biochemical improvements in a dorsal random flap rat model. For ASH editorial purposes, the trial supports the mechanistic basis of leech therapy in flap salvage and adds preclinical support to the K040187-cleared indication. For US clinicians, the trial does not change practice but does provide modern animal-model evidence that the venous-decongestion mechanism is biologically operative. The saliva extract finding also supports future research on purified leech-derived biologics as alternatives to whole-leech device therapy.
Related Trials
Medicinal leech therapy in venous congestion of microsurgical flaps: a randomized comparison with heparin pinprick scarification
Merlino G, Carbone S, Servillo G, Marletta DA (2020)
Adjunctive medicinal leech therapy for venous congestion in free flaps: a German multicenter randomized trial
Lehnhardt M, Daigeler A, Behr B, Schmidt SV, Wallner C (2021)
Medicinal leeches and the microsurgeon: a four-year study, clinical series and risk benefit review
Whitaker IS, Josty IC, Hawkins S, Azzopardi E, Naderi N, Graf J, Damaris L, Lineaweaver WC, Kon M (2011)
Medicinal leeches for surgically uncorrectable venous congestion after free flap breast reconstruction
Pannucci CJ, Nelson JA, Chung CU, Fischer JP, Kanchwala SK, Kovach SJ, Serletti JM, Wu LC (2014)