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. 

In This Article


Retrospective Review

The study included a total of 51 patients with 58 DFUs. The participants were comprised of 13 (25.49%) women and 38 (74.51%) men, with a mean age of 66 years (range, 45–88 years). Patient demographics are listed in Table 1. The mean number of comorbidities per patient was 4.73 (Figure 1). Hemoglobin A1c data were available for 50 (98.04%) of the 51 patients. The overall mean HbA1c was 7.45%, and the mean HbA1c for healed patients was 7.34% and 7.6% for nonhealed wounds.

Figure 1.

Patient comorbidities.
COPD: chronic obstructive pulmonary disease; CHF: chronic heart failure; CKD: chronic kidney disease; CAD: coronary artery disease; PVD: peripheral vascular disease; GERD: gastroesophageal reflux disease; HTN: hypertension; DM: diabetes mellitus

Ten patients (19.61%) had an abnormal ABI result. Although ABI results were abnormal, 6 patients (60%) fully healed their wounds. Furthermore, a total of 8 abnormal ABI patients (80%) had > 97% of wound surface area healed.

The mean initial wound size was 3.02 cm2 (range, 0.04 cm2–15.0 cm2). The locations of the wounds were as follows: 17 (29.31%) toe, 14 (24.14%) forefoot, 17 (29.31%) midfoot, 5 (8.62%) heel, and 5 (8.62%) dorsal foot (Figure 2). Wounds were classified based on Wagner grades: 43 (74.14%) grade 1, 11 (18.97%) grade 2, and 4 (6.90%) grade 3 (Figure 3). The mean ulcer duration at initial graft application was 18 weeks (range, 1–156 weeks).

Figure 2.

(A) Wound location and (B) number of wounds healed per location.

Figure 3.

(A) Wagner grade of studied ulcers and (B) number of wounds healed based on grade.

The total number of feet (right and left) with wounds was 54; however, only 34 had documentation indicating the type of offloading used. The 34 documented cases were evaluated based on offloading used (Figure 4). A total of 19 feet (55.88%) healed using a form of offloading. Of the 19 healed feet, 15 (78.95%) used a modified controlled ankle movement boot or postoperative shoe (Figure 4).

Figure 4.

Wound offloading and number of healed wounds per each type of offloading.
CROW: Charcot restraint orthotic walker

At 16 weeks, there was a mean reduction of wound surface area by 87.57%, and 35 of 58 (60.34%) wounds fully healed (Figure 5). By 16 weeks, > 90% reduction in surface area was achieved in 43 DFUs (74.14%) and > 75% reduction was seen in 49 (84.48%). There were only 2 wounds that saw no reduction in surface area at 16 weeks; both wounds healed eventually, with 1 healed at 24 weeks after 2 additional applications of acellular fish skin graft. The other healed at 36 weeks with only 3 additional wound debridements and no additional acellular fish skin graft applications; it should be noted that this wound was the oldest and had been present for more than 3 years.

Figure 5.

The average percentage of wound surface area healed per week.
Avg: average; SA: surface area; wk: week

The mean number of acellular fish skin graft applications per patient was 4.9. The mean time to achieve wound healing in the 35 fully healed wounds was 10 weeks. The mean number of grafts used on fully healed patients was 4.5 (Table 2).

Systematic Review

A total of 10 articles met inclusion criteria for the literature review, either from initial PubMed review or from additional search of the literature. The current literature indicates that fish graft has benefits in many fields of medicine, including neurology, dentistry, and wound care (Table 3 [7,9,14–18]).

Three studies evaluated fish skin grafts for strictly lower extremity wounds (Table 4[10,13,19]). Cyrek et al[19] presented a case study of an 86-year-old patient with a chronic lower extremity venous ulcer in which the ulcer healed within 14 weeks with fish graft applications. Trinh et al[13] completed a larger case study with 7 complicated wounds (bone exposed). Five forefoot wounds took 13 to 41 weeks to heal. It was noted that wound area decreased significantly by 50% in the first third of treatment time. Yang et al[10] evaluated wound healing in 18 patients with chronic lower extremity ulcers over 5 weeks. Similar to Trinh et al,[13] they[10] found wound surface area and wound depth had decreased by 40% and 48% at 5 weeks, respectively. Also at 5 weeks, Yang et al[10] noted 3 of 18 wounds (16.67%) healed.