Acellular Fish Skin as a Bridge to STSG in Open Transmetatarsal Amputations: Early Outcomes, Protocol, and Pearls

Medical education note: This article is for clinicians. Always follow device IFUs and local protocols.

Quick take (TL;DR)

In patients undergoing open transmetatarsal amputation (TMA) for severe infection or ischemia, staged closure using acellular fishskin graft (FSG) to build granulation before split-thickness skin grafting (STSG) led to progressive granulation, no higher-level amputations, maintenance or improvement in ambulation, and no graft-related adverse events in this early experience—findings that mirror published data showing that acellular fish skin grafts can significantly increase healing rates and reduce time to closure in complex diabetic foot ulcers compared with standard care.[1,2]

Why consider fish skin in open TMA?

Healing open midfoot/TMA wounds is notoriously difficult—poor perfusion, bioburden, and systemic comorbidities often stall progress and drive more proximal amputations, and large series report TMA healing rates in the 40–80% range with substantial risk of higher-level amputation.[11,12] A piscine acellular dermal matrix derived from cod skin provides a 3D scaffold with collagen and omega-3 lipids that may support granulation, epithelialization, angiogenesis, and modulation of local inflammation, creating a more favorable bed for later STSG.[3,4]

What the team did (methods in brief)

(Patient healing from open mid-foot amputation with fish skin graft applied in the first week)

Population: Patients who required open TMA for severe soft-tissue infection or ischemia, a group known to have high rates of wound-healing complications and reoperation in contemporary TMA outcome studies.[13,14]

Approach: After debridement and amputation, fishskin graft was placed on the open amputation site and managed with standard offloading and wound care, consistent with guidelines that recommend advanced skin substitutes only as adjuncts to best-practice multidisciplinary care for diabetic foot ulcers.[15,16]

Staging: Once complete granulation developed, the team proceeded to STSG for definitive coverage, following the same staged “biologic bridge then autograft” strategy described in case series where fish skin supports rapid granulation prior to skin grafting.[4,11]

Outcomes at a glance

(Photo shows patient healing from mid foot amputation after six weeks with fish skin graft applied)

Granulation: All cases showed consistent, progressive granulation after FSG placement, with granulation sufficient for STSG typically achieved in ~3–6 weeks under standard offloading and wound care, aligning with reported re-epithelialization and closure timelines when AFSGs are used in chronic diabetic foot wounds.[6,8]

Limb salvage: No patient required delayed primary closure or a higher-level amputation in this series, which compares favorably with modern TMA cohorts where 20–30% of patients often progress to more proximal amputations despite aggressive care.[11,14]

Function: Ambulatory status was maintained or improved during recovery, consistent with evidence that successful TMA healing preserves independent ambulation and function in a large proportion of patients when distal limb length can be saved.[13]

Safety: No graft-related complications (allergic reactions, infections, or rejection) were reported, in line with broader data showing low rates of adverse events and no autoimmune reactions in patients treated with acellular fish skin grafts.[1,6]

How to run a staged FSG → STSG pathway (clinic playbook)

Debride aggressively; control infection.
Perform thorough surgical debridement and ensure systemic antibiotics and microbial control per contemporary diabetic foot infection guidelines before placing any advanced biologic.[16]

Apply FSG to the open TMA site.
Secure the fishskin graft per protocol and institute standard offloading and supportive wound care, using it as an adjunct to—not a replacement for—established multidisciplinary ulcer management.[15]

Watch for the granulation milestone.
Expect roughly 3–6 weeks for a healthy, uniform bed capable of accepting STSG, and document trajectory with serial photos and measurements, echoing protocols used in prospective evaluations and randomized trials of AFSGs.[1]

Proceed to STSG.
Once fully granulated, perform split-thickness skin grafting for durable coverage, as described in case series where fish skin acts as a temporary matrix before autologous grafting in complex lower-extremity defects.[4,11]

Rehab + offloading.
Continue protective offloading and progressive ambulation to maintain function while the grafts mature, aligning with limb-salvage and offloading principles recommended for post-amputation and post-ulcer patients.[11,15]

Why this matters for limb-salvage programs

Open midfoot/TMA wounds in high-risk patients are prone to delayed closure and complication cascades; TMA series consistently show that a significant minority of patients require progression to below-knee amputation or have prolonged non-healing despite intensive care. This staged approach positions FSG as a biologic bridge, buying time for granulation and epithelial advance while avoiding wound deterioration, potentially lowering the need for proximal amputation in a population already known to face high morbidity and mortality.[11, 12, 14]

Limitations (read before you generalize)

This is an early, uncontrolled experience without a comparator arm; larger prospective cohorts are needed to confirm efficacy, define ideal patient selection, and clarify cost-effectiveness, just as recent meta-analyses and narrative reviews have called for more high-quality randomized data on AFSGs. Still, the uniform granulation response, preserved function, and absence of complications observed here are directionally consistent with randomized trials and prospective series showing higher closure rates and favorable safety profiles with fishskin compared with conventional care.[1,8]

Clinician FAQ

When should I consider FSG after TMA?
Consider AFSG when delayed primary closure is not feasible and you need a granulating bridge to prepare for STSG in the setting of infection, ischemia, and systemic comorbidities—an approach supported by data showing AFSGs can accelerate healing in difficult diabetic foot ulcers when added to best-practice care.[2]

How long until I can graft?
Based on this early experience and AFSG outcome data, you can expect approximately 3–6 weeks to achieve an STSG-ready bed, with many chronic lower-extremity wounds in published series reaching complete closure over 10–16 weeks when managed with serial fish-skin applications.[6]

Did patients lose function while waiting?
In this series, ambulation was maintained or improved, and broader TMA literature confirms that successful healing at the transmetatarsal level is strongly associated with better functional and patient-reported outcomes compared with more proximal amputations.[13,18]

Any graft-related complications?
No graft-related complications were observed, and randomized and prospective AFSG studies likewise report low rates of local adverse events, with no device-related serious complications and low recurrence rates after ulcer closure.[1]

Bottom line

For complex open TMA wounds in high-risk patients, acellular fishskin can serve as a biologic bridge that reliably builds a graft-ready bed in a few weeks, enabling STSG while preserving ambulation and avoiding more proximal amputation—a practical, low-morbidity addition to the limb-salvage toolbox that is increasingly supported by RCTs, cohort studies, and evidence-based guidelines on adjunctive wound-healing interventions.[1,15]

References

[1] Lantis JC II, Lullove EJ, et al. Final efficacy and cost analysis of a fish skin graft vs standard of care in the management of chronic diabetic foot ulcers. Prospective multicenter RCT showing significantly higher healing rates and cost savings with AFSG vs conventional advanced therapy.
Link: https://pubmed.ncbi.nlm.nih.gov/37023475/

[2] Zhao Y, et al. Acellular fish skin grafts in diabetic foot ulcer care. Meta-analysis reporting improved complete healing and shorter healing time with AFSGs compared with standard therapy.
Link: https://pmc.ncbi.nlm.nih.gov/articles/PMC11718459/

[3] Esmaeili A, et al. Acellular fish skin for wound healing. Int Wound J. 2023. Review of decellularization methods, structural properties, and clinical applications of fish-skin grafts.
Link: https://pmc.ncbi.nlm.nih.gov/articles/PMC10410342/

[4] Cherry I, et al. Exploring the place of fish skin grafts with omega-3 in pediatric wound care. J Clin Med. 2023;13(1):112. Includes a surgical protocol and case series showing fishskin as a scaffold prior to definitive closure.
Link: https://www.mdpi.com/2077-0383/13/1/112 MDPI

[5] Use of Fish Skin in the Treatment of Chronic Lower Extremity Wounds: A Case Series Report. Demonstrates progressive granulation and closure in complex lower-extremity wounds treated with serial fish-skin grafts.
Link: https://www.gavinpublishers.com/article/view/use-of-fish-skin-in-the-treatment-of-chronic-lower-extremity-wounds-a-case-series-report edfn.org

[6] Khan MA, et al. Omega-3 acellular fish skin grafts for chronic and acute wounds. J Dermatolog Treat/Diabetic Foot & Ankle (2025). Narrative review noting accelerated healing, reduced pain, and no autoimmune reactions with AFSGs.
Link: https://dpcj.org/index.php/dpc/article/view/4945 Dermatology Practical & Conceptual

[7] Ruiz-Muñoz M, et al. Fish skin grafts versus standard of care on wound healing in diabetic foot disease. RCT showing higher complete healing rates with fishskin than with standard care.
Link: https://www.sciencedirect.com/science/article/pii/S175199182400072X

[8] Woodrow T, Chant T, et al. Treatment of diabetic foot wounds with acellular fish skin graft rich in omega-3: A prospective evaluation. J Wound Care. 2019. Reports high closure rates and good tolerance of AFSGs.
Link: https://www.kerecis.com/publications/Kerecis

[9] Esmaeili A, et al. Processing and post-processing of fish skin as a novel biomaterial for wound healing. Discusses how decellularization and post-processing preserve biomechanical and biological properties of fish skin.
Link: https://www.sciencedirect.com/science/article/abs/pii/S0040816623002264 ScienceDirect

[10] Chen W, et al. Decellularization of fish tissues for tissue engineering and regenerative medicine. Regen Biomater. 2025. Reviews state-of-the-art methods to prepare acellular fish tissues and their advantages.
Link: https://academic.oup.com/rb/article-lookup/doi/10.1093/rb/rbae138 OUP Academic

[11] Truong DH, et al. Success of transmetatarsal amputation for limb salvage in patients with diabetic foot disease. Reports >75% limb-salvage success with adequate runoff, but notable non-healing and re-amputation rates.
Link: https://pmc.ncbi.nlm.nih.gov/articles/PMC10781589/

[12] Joyce A, et al. Transmetatarsal amputation: A 12-year retrospective case series. Foot Ankle Surg. 2020;26(6):700–706. Found 78% TMA healing, 11% major amputation, and median healing time ~83 days.
Link: https://pubmed.ncbi.nlm.nih.gov/32032924/

[13] Landry GJ, et al. Predictors of healing and functional outcome following transmetatarsal amputations. JAMA Surg. 2011. Shows association between healed TMA and improved functional outcomes and ambulation.
Link: https://jamanetwork.com/journals/jamasurgery/fullarticle/1107141 JAMA Network

[14] Tokarski AR, et al. Are transmetatarsal amputations a durable limb salvage procedure? J Foot Ankle Surg. 2022. Reports TMA healing times, re-ulceration, and re-amputation rates in a contemporary cohort.
Link: https://www.jfas.org/article/S1067-2516(21)00391-4/abstract

[15] Chen P, et al. Guidelines on interventions to enhance healing of foot ulcers in people with diabetes (IWGDF 2023 update). Evidence-based recommendations for advanced wound-healing interventions as adjuncts to gold-standard care.
Links: https://pubmed.ncbi.nlm.nih.gov/37232034/
– Full guideline PDF: https://iwgdfguidelines.org/wp-content/uploads/2023/07/IWGDF-Guidelines-2023.pdf IWGDF Guidelines

[16] Senneville É, et al. IWGDF/IDSA Guidelines on the diagnosis and treatment of diabetic foot infections. Clin Infect Dis. 2023. Provides guidance on debridement, infection control, and antibiotic stewardship in DFIs.
Link: https://academic.oup.com/cid/advance-article/doi/10.1093/cid/ciad527/7287196 OUP Academic

[17] Evaluating the Effect of Omega-3–Rich Fish Skin in the Treatment of Chronic, Nonresponsive Diabetic Foot Ulcers. Prospective RCT showing improved healing with AFSG in chronic DFUs.
Link: https://www.hmpgloballearningnetwork.com/site/wounds/rapid-communication/evaluating-effect-omega-3-rich-fish-skin-treatment-chronic

[18] Deldar R, et al. Functional and patient-reported outcomes following transmetatarsal amputation. Plast Reconstr Surg Glob Open. 2022. Retrospective review linking successful TMA healing with favorable functional outcomes.
Link: https://journals.lww.com/prsgo/fulltext/2022/05000/functional_and_patient_reported_outcomes_following.62.aspx Lippincott Journals

[19] DynaMed. Management of Diabetic Foot Ulcer. Summary of evidence and guideline-based best practices, including IWGDF wound-healing recommendations.
Link: https://www.dynamed.com/management/management-of-diabetic-foot-ulcer dynamed.com