Acellular Fish Skin Graft use for Diabetic Lower Extremity Wound Healing

A Retrospective Study of 58 Ulcerations and a Literature Review

Shannon Michael, DPM; Christopher Winters, DPM; Maliha Khan, DPM

Wounds. 2019;31(10):262-268.

Conclusions

The results of this 3-year retrospective study support increased wound healing rates with the use of acellular fish skin graft for treatment of DFUs. Furthermore, rapid wound surface area reduction during the initial 4 weeks following graft application corroborates previous research^[10,13] that acellular fish skin graft enables the DFU to transition from a chronic inflammatory stage to an acute wound environment for healing.

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Table 1. Patient demographics
DEMOGRAPHIC	N=51
Gender (n)
Male	38
Female	13
Age (y)
Mean	66
Median (range)	67 (45–88)
HbA_1c (%)
Mean	7.45
Median (range)	7.2 (7.0–10.8)
Wound duration (wk)
Mean	18
Median (range)	8 (1–156)
Initial wound area (cm²)
Mean	3.02
Median (range)	1.31 (0.04–15.0)

y: year; HbA_1c: hemoglobin A_1c; wk: week

Table 2. Wound healing at 16 wk and number of grafts used per wound
WOUNDS & GRAFTS	N
Healed wounds	35 (60.34%)
Wounds with >90% SA healed	43 (74.14%)
Wounds with >75% SA healed	49 (84.48%)
Mean grafts used per wound	4.9
Mean grafts used on healed wounds	4.5

wk: week; SA: surface area

Table 3. Literature review of fish graft
ARTICLE (Y)	LOE	METHOD	PARTICIPANTS (N)	RESULTS	CONCLUSIONS
Baldursson¹⁴ (2015)	I	Double-blind, randomized, controlled clinical trial. Each patient had two 4mm full-thickness wounds. Treated with porcine or fish graft.	81 patients; 162 full-thickness forearm wounds	At 2 wk, 13% fish graft and 6% porcine graft wounds had healed. At 3.5 wk, 77.5% fish graft and 65% of porcine graft wounds had healed.	Fish skin graft showed significantly faster healing than porcine matrix.
Dragan¹⁸ (2017)	IV	A case study. Fish graft used to treat mucogingival deformity (lack of keratinized tissue).	1 patient	Wk 4 showed visual indications of keratinization. At 6 mos, the width of the keratinized tissue was 4mm.	Fish graft increased keratinized tissue in dental deformity.
Dorweiler¹⁷ (2017)	IV	Multicenter case study to evaluate vascular and/or diabetic wound healing with acellular fish skin graft.	23 patients with 25 wounds (thigh n=2; calf n=7; forefoot n=14; hand n=2)	9 to 41 wk until wound healing was established. 3 to 26 acellular fish skin grafts applied per wound.	Fish graft supports wound healing for vascular and diabetic ulcerations.
Kjartansson⁹ (2015)	IV	Animal pilot study. Evaluated fish graft for dura mater substitute. At 2, 5, 8, and 11 wk, neuroimaging (MRI), necropsy, and histological analysis of fish graft used for dura repair were performed.	4 adult sheep	Necropsy: At 11 wk, no adhesion, cerebral surface normal, and fish graft slightly visible and excelling integration into surrounding dura. MRI: No subdural fluid collection or cerebral inflammation. Histology: at 2 wk, neutrophilic inflammation; 5 wk, inflammatory changes decreased; and 8 wk, angiogenesis.	Graft acts as a host for cellular ingrowth and allows for neodura formation. No graft rejection or reactions.
Magnusson¹⁵ (2017)	IV	Evaluate cell ingrowth capabilities and bacterial properties of acellular fish skin graft and dHACM.	6 fish graft; 6 dHACM	Fish skin highly porous compared with dHACM. Fish graft superior ability to support 3D ingrowth of cells.	Bacterial barrier present for 24 to 48h for fish skin graft. Fish graft shows superior cell ingrowth ability to dHACM.
Magnusson⁷ (2016)	III	Literature review.	5 fish graft articles reviewed	Fish graft contains proteins and lipids (omega-3) that may help the wound escape the chronic inflammation state. Fish graft can be used in acute and chronic wounds.	Literature supports fish skin increases cell ingrowth, reduces need for analgesic medication, creates bacterial barrier, and reduces wound care costs.
Magnusson¹⁶ (2015)	III	Examined the structure of fish skin microscopically. Protein from fish graft was analyzed using gel electrophoresis.	Rabbits, mice, rats, hamster, chick embryo	Acellular fish skin administered to mice did not show signs of toxicity. No fever or skin inflammation caused in rabbits. Chick chorioallantoic membrane assay indicated greater angiogenesis compared to controls.	Fish graft contains collagen I, which encourages angiogenesis and cell ingrowth. Fish skin is nontoxic and has more bioactive compounds than mammalian grafts.

y: year; LOE: level of evidence; wk: week; mos: month; MRI: magnetic resonance imaging; dHACM: dehydrated human amnion/chorion membrane; h: hour

Table 4. Literature review of fish graft use for lower extremity wounds
ARTICLE (Y)	LOE	METHOD	PARTICIPANTS (N)	RESULTS	CONCLUSIONS
Cyrek¹⁹ (2017)	IV	IV A case study. Fish graft used for chronic venous lower extremity ulcer.	1 patient	At 14 wk the wound completely healed.	Lower extremity venous ulcer healed with fish graft.
Trinh¹³ (2016)	IV	A case study. Evaluated diabetic patients with complicated lower extremity wounds (bone exposed).	5 patients with 7 total wounds (2 thigh, 5 forefoot)	Thigh wounds took 26 wk to heal. Forefoot wounds healed from 13 to 41 wk. Pain level was reduced within first 2 wk. Wound area decreased by 50% within first third of treatment time.	Fish graft reduced pain. Wound area decreased significantly during first third of treatment time.
Yang¹⁰ (2016)	IV	A prospective observational study. Evaluated lower extremity wound healing with 5 weekly fish skin graft applications followed by 3 wk of standard wound care.	18 patients	At 5 wk, 40% decrease in wound surface area and 48% decrease in wound depth. 3 of 18 wounds healed at 8 wk.	Fish graft supports lower extremity wound healing.

y: year; LOE: level of evidence; wk: week

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Acellular Fish Skin Graft use for Diabetic Lower Extremity Wound Healing

A Retrospective Study of 58 Ulcerations and a Literature Review

Conclusions

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A Retrospective Study of 58 Ulcerations and a Literature Review

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