Acellular Fish Skin for Deep Dermal Traumatic Wounds Management: A Case Report

ABSTRACT

Wound dressings play a critical role in minimizing systemic inflammation and promoting scar‐free healing. Among them, extracellular matrix (ECM)‐based materials enriched with bioactive components show promise in accelerating tissue repair and regeneration. In this case report, deep dermal traumatic wounds of a 34‐year‐old woman were treated with a combination of platelet‐rich fibrin gel (PRF), plasma‐rich growth factor gel (PRGF), and acellular fish skin (AFS) grafts. Objective and subjective assessments were performed over a one‐year follow‐up period. The wounds treated with AFS demonstrated significantly faster healing, improved water retention, reduced pain, and superior functional and aesthetic outcomes compared to conventional treatments. Improvements included enhanced skin elasticity, thickness, and pigmentation. The synergistic application of PRF, PRGF, and decellularized fish skin grafts may serve as an effective alternative to split‐thickness skin grafts for managing deep dermal wounds, offering accelerated healing and improved long‐term outcomes.

Key Clinical Message

This case demonstrates that acellular fish skin grafted with autologous PRF and PRGF effectively manages extensive wounds, achieving excellent healing without a skin graft. This biologic approach avoids donor‐site morbidity, offering a promising alternative for complex wound care.

1. Introduction

The management of complex wounds has evolved significantly with the introduction of advanced biomaterials and bioactive therapies, with the aim of reducing healing time, minimizing complications, and improving cosmetic and functional outcomes. Traditional wound dressings often fail to provide the optimal microenvironment required for tissue regeneration, particularly in large, full‐thickness traumatic injuries [1]. An ideal response to an advanced treatment is the use of suitable biomaterials as wound dressings, which, in addition to being biocompatible and not causing inflammatory reactions, can allow the presence and activity of cells and angiogenesis, which can lead to the production of new tissue over time [2, 3, 4]. Studies have shown that matrices, as biocompatible products, are a suitable alternative to synthetic biomaterial‐based products for advanced wound treatment [4]. Matrices with three‐dimensional architecture and suitable biochemical components provide an environment for cell growth, proliferation, and activity. The use of matrices similar to the structure of human skin can provide an ideal extracellular environment for the production of replacement tissue [1, 4]. Allogeneic and xenogeneic skin substitutes do not have the limitations of using autologous skin, but the process of decellularization and removal of irritants, especially when using mammalian skin, has limited access due to the possibility of transmitting common diseases between humans and animals [5, 6]. Skin substitutes from pig, bovine, or human cadaver skin pose cultural and religious challenges in addition to problems such as autoimmune responses and infections [7].

In recent years, biological skin substitutes have emerged as promising alternatives that provide a three‐dimensional structure that supports cells due to their unique structural and immunological properties. Unlike mammalian‐derived products, AFS is free from the risk of zoonotic transmission and immunogenic responses, and it avoids cultural and religious limitations often associated with porcine or bovine grafts. Additionally, AFS retains essential components such as omega‐3 fatty acids, which may contribute to its anti‐inflammatory and antimicrobial effects [8, 9]. Recently, a product from the Kerecis Company (Iceland), which uses a novel skin substitute derived from acellular fish skin, has received much attention for the treatment of burn patients. In addition to having a three‐dimensional architecture with a porous microstructure that allows cells to migrate, proliferate, and grow, decellularized fish skin also offers potential benefits such as anti‐inflammatory and antimicrobial properties [10]. Incorporation of AFS with autologous growth factors, such as platelet‐rich fibrin (PRF) and plasma‐rich growth factor (PRGF), may further enhance the regenerative potential. PRGF and PRF release a potent combination of cytokines and growth factors that promote angiogenesis, fibroblast activity, and epithelial cell migration, thereby accelerating wound healing. Furthermore, when used in combination with negative pressure wound therapy (NPWT), the wound bed can be optimized prior to grafting, enhancing graft uptake and integration [11].

In this report, we present a case of a patient with a deep dermal traumatic wound which was successfully treated through a sequential protocol involving surgical debridement, NPWT, application of PRGF/PRF, and AFS grafting. The patient's outcomes regarding healing and scar quality were collected objectively and subjectively for 2 months after the injury.

2. Case Presentation and Procedure

A 34‐year‐old female, height 180 cm and weight 108 kg, was referred to Prophets Hospital with a deep dermal traumatic wound located on the anterior thigh after a physical altercation. Written informed consent from the patient was obtained according to journal guidelines. The patient had sustained a direct blow to the thigh with a subsequent impact of the thigh against a curb. This resulted in the formation of a significant hematoma in the thigh. The mechanism of injury involved blunt trauma from a kick and contusion on a hard surface. The clinical presentation, diagnostic evaluation, and management strategies for traumatic thigh hematomas were discussed. On admission, the patient was hemodynamically stable. Laboratory evaluations revealed elevated inflammatory markers, including an erythrocyte sedimentation rate (ESR) of 70 mm/h and a C‐reactive protein (CRP) level of 50 mg/dL. The patient had no underlying medical conditions such as diabetes, malnutrition, peripheral vascular disease, or immunodeficiency. The wound size was approximately 25 × 15 cm, indicating a large full‐thickness skin defect. A significant subcutaneous hematoma developed at the wound site within the first 10 days after the trauma. Clinically, the area appeared swollen and discolored, with palpable fluid accumulation and tense overlying skin. The presence of the hematoma resulted in increased pressure on surrounding tissues and posed a risk for secondary necrosis and delayed healing. To prevent further complications, the hematoma was surgically drained under sterile conditions (Figure 1a). The evacuation of the hematoma revealed an open wound bed with fresh granulation tissue, but necrotic margins were also present, necessitating serial debridement (Figure 1a–c). Immediately after drainage, Negative Pressure Wound Therapy (NPWT) was initiated. A polyurethane foam dressing was applied and sealed with an occlusive film, connected to a vacuum system set to −125 mmHg. This intervention served to remove residual exudate, relieve tissue pressure, reduce edema, and stimulate perfusion and granulation. The patient underwent wound debridement every 48 h during the NPWT course, which was maintained for 2 weeks. Once the wound was adequately prepared, an acellular fish skin (AFS) graft was applied in combination with autologous platelet‐rich fibrin (PRF) and plasma rich in growth factors (PRGF) (Figure 1d). The graft was placed without sutures and adhered successfully (Figure 1e,f). Follow‐up showed excellent integration, and complete epithelialization was achieved within 60 days post‐intervention. The patient was treated with fish skin transplantation and growth factors. In a previous study [12], decellularized fish skin was subjected to various in vitro and in vivo evaluations and finally [13] successfully received the permission for clinical evaluation from the Ethics Committee of Shahid Beheshti University of Medical Sciences (Iran; Ethics Code: IR.SBMU.REC.1398.059 and Clinical Trials Code: IRCT20190826044620N1). Briefly, fresh Grass Carp skin (Mazandaran Fish Farm, Tonekabon, Iran) was prepared and then decellularized with hypotonic and hypertonic solutions, Triton X100 (0.5% w/v; 24 h), and finally washed with PBS and cold distilled water, and finally freeze‐dried. The resulting acellular fish skin was approximately 0.25 mm thick. The samples were sterilized with gamma radiation before transplantation. Peripheral venous blood was collected from the patient in sterile tubes and immediately processed via a single‐step centrifugation protocol (at 3000 rpm for 10 min) to obtain Platelet‐Rich Growth Factor (PRGF) and Platelet‐Rich Fibrin (PRF) fractions [12, 13]. Following separation, the PRGF (liquid fraction) was aspirated and directly applied over the wound bed, while the PRF (clot‐like matrix) was layered onto the wound to provide a sustained source of growth factors and cellular scaffold. This biological combination was applied without suturing and replaced weekly for a period of 1 month (Figure 1d).

FIGURE 1.

(a) Wound appearance on day 10 prior to hematoma drainage (hematoma with bruising and superficial abrasion), (b) Wound bed following hematoma evacuation (early granulation visible), (c) After serial debridement during NPWT (mature granulation tissue), (d) Isolated PRGF/PRF fractions, (e) acellular fish skin, (f) Application of growth factors with AFS graft without sutures (wound size: ~20 × 12 cm).

3. Results and Discussion

The wound healing process, as measured by wound surface area at different time points (based on multiple‐column t‐tests, p < 0.001), indicates a favorable response to the combined treatment with PRGF, PRP, and acellular fish skin (AFS). All measurements were compared with the patient's healthy skin as a control. Table 1 shows the wound healing progress at different times. Overall, the results demonstrated that this combined therapy was able to achieve complete wound closure by the 60th day.

TABLE 1.

Wound dimensions and healing timeline.

Day	Wound size (cm)	Treatment step	Clinical observation
10	25 × 15	Post‐trauma hematoma	Swelling, discoloration
10	25 × 15	Hematoma evacuation	Exposed wound, granulation begins
12–24	~20 × 12	NPWT + debridement	Improved granulation, necrosis reduced
24	~15 × 10	AFS + PRGF/PRF grafting	Strong adherence, no infection
60	Healed	Final epithelialization	No scar contracture, functional coverage

Figure 1 shows the healing process of the wound after 60 days. Figure 2a shows advanced epithelialization after the application of PRGF/PRF/AF, As can be seen in the figure, the wound surface is covered with granulation tissue and the epithelial margin is advancing. Ongoing epithelialization was observed approximately 2 weeks after AFS application, with remaining graft matrix remnants (Figure 2b). The wound bed was almost fully re‐epithelialized with minor exudate; early signs of remodeling and wound contraction were observed (Figure 2c). Figure 2d shows the final scar appearance at the 2‐month follow‐up; no signs of infection or graft rejection; satisfactory aesthetic and functional outcome.

FIGURE 2.

(a) Epithelialization after PRGF/PRF/AFS application, (b) Ongoing epithelialization approximately 2 weeks, (c) Wound bed almost fully re‐epithelialization with minor exudate, (d) Final scar appearance at 2‐month follow‐up.

Platelets are a rich source of growth factors and cytokines that have been shown to promote wound healing. Growth factors play a key role in processes such as angiogenesis, migration, proliferation, and differentiation of cells, which can increase extracellular matrix secretion [14]. Platelet‐derived growth factors [15] are a promising option for wound healing due to their ease of extraction, availability, cost‐effectiveness, and safety [16]. Our previous study in an animal model showed that the use of PRGF/PRF combined with a decellularized fish skin scaffold can accelerate the regeneration process [17]. Several studies have shown that such factors may inhibit inflammation and accelerate the process of epithelialization and wound closure [18, 19]. The presence of substances such as type I collagen and elastin in fish skin can stimulate fibroblast growth factor (FGF) and keratinocyte growth factor (KGF), two cytokines important for wound healing. In addition, the use of such a dressing, in addition to maintaining tissue moisture, acts as a protective barrier against bacterial entry [20, 21]. Evaluation of Nile tilapia skin as a biological wound healing stimulator in a canine animal model showed wound healing after 2 weeks [9].

A randomized phase III trial was conducted on 115 patients with superficial burns (15% thickness or less) treated with glycerolized fish skin compared with 1% silver sulfadiazine cream. Patients treated with fish skin required fewer days for epithelial regeneration and fewer dressings. Finally, the use of fish skin showed a 42.1% reduction in the average final cost of treatment per patient [22]. A phase II trial of fish skin grafting was also conducted in 62 patients in terms of healing time, number of dressing changes during treatment, and pain intensity. The results of this study showed that patients using fish skin required fewer dressing changes during the epithelialization process, and a significant reduction in pain was also reported in patients treated with Nile tilapia skin [21].

The present case demonstrates the successful management of a large full‐thickness traumatic wound on the anterior thigh using a combined approach of acellular fish skin (AFS) grafting and autologous platelet‐derived products including PRGF and PRF, without the need for mesh grafting or suturing. The patient's wound, initially measuring 25 × 15 cm², showed remarkable healing progression following the integration of negative pressure wound therapy (NPWT), repeated debridement, and subsequent biological dressing. AFS provides an extracellular matrix rich in omega‐3 fatty acids, collagen, and other native components, which support cellular migration and tissue regeneration. The decellularized fish skin used in this case was applied without sutures and showed excellent adherence, integration, and no evidence of infection or rejection throughout the treatment course [17]. The application of PRGF and PRF further enhanced wound healing by delivering autologous growth factors and forming a natural fibrin scaffold, thus accelerating re‐epithelialization and tissue remodeling. Unlike conventional mesh grafts that often require surgical fixation and may result in donor site morbidity or undesirable cosmetic outcomes, the AFS + PRGF/PRF strategy enabled rapid granulation and epithelial coverage while preserving skin texture and elasticity. Notably, the complete healing of the wound was achieved within approximately 60 days, with minimal scarring and full restoration of local tissue integrity, which emphasizes the efficacy and safety of this combined modality. These findings are consistent with our previous study involving a human model with severe wounds, where the combination therapy also led to enhanced healing outcomes. The results of this study are similar to our previous study on a human model with severe wounds [17]. The present case demonstrates the successful management of a large full‐thickness traumatic wound using a combined approach of acellular fish skin (AFS) grafting and autologous platelet‐derived products (PRGF/PRF), supported by NPWT and repeated debridement. This multimodal protocol enabled rapid granulation, epithelial coverage, and favorable cosmetic outcomes without the need for mesh grafting. AFS, due to its unique structural and biological properties, acted as a bioactive scaffold rich in collagen, elastin, and omega‐3 fatty acids. These features preserved tissue hydration, reduced inflammation, and facilitated cellular infiltration and angiogenesis. In parallel, PRGF and PRF provided essential cytokines and growth factors that promoted fibroblast activity, keratinocyte migration, and angiogenesis. The interaction of these modalities resulted in accelerated re‐epithelialization and improved scar quality compared with conventional treatment methods. Nevertheless, several limitations must be acknowledged. The follow‐up period was relatively short (2 months), which does not allow conclusions regarding the long‐term durability of the outcomes. In addition, patient‐reported outcomes such as pain intensity, mobility, and return to daily activities were not systematically assessed. Including such data in future studies would provide a more comprehensive evaluation of treatment effectiveness. In conclusion, the combination of AFS with autologous growth factors provided a safe, biologically active, and clinically effective approach that resulted in complete wound closure within 60 days and satisfactory aesthetic and functional outcomes. Despite the limitations, this case supports the growing evidence that AFS, when combined with platelet‐derived products, may serve as a valuable alternative to traditional skin grafting in complex traumatic wounds.

4. Conclusion

The combined use of autologous growth factors and acellular fish skin (AFS) graft demonstrated significant potential in promoting rapid and functional healing in a deep dermal traumatic wound. The integration of Negative Pressure Wound Therapy (NPWT) as an initial wound management strategy enhanced granulation tissue formation and optimized the wound bed for subsequent grafting. This multimodal approach not only accelerated epithelialization and wound closure but also improved tissue hydration, elasticity, and cosmetic outcomes. The treatment was well tolerated, with no signs of infection or immunological complications. This case supports the clinical feasibility and effectiveness of incorporating AFS and biologic agents into the standard wound care protocol, particularly in complex full‐thickness injuries. However, further large‐scale, controlled clinical trials are required to validate these findings and establish definitive guidelines.

Author Contributions

Esmaeil Biazar: conceptualization, formal analysis, investigation, methodology, project administration, supervision, validation, writing – original draft. Saeed Heidari‐Keshel: conceptualization, formal analysis, investigation, methodology, project administration, supervision, validation, writing – original draft. Mahdiye Sadat Rezaee: formal analysis, investigation, resources, software, validation, visualization. Parisa Parsi: data curation, formal analysis, investigation, methodology, resources, software, validation. Hamideh Moravvej: data curation, formal analysis, investigation, methodology, resources, software, validation, visualization. Majid Rezaei Tavirani: data curation, formal analysis, investigation, methodology, validation, visualization. Mostafa Rezaei Tavirani: conceptualization, data curation, funding acquisition, investigation, project administration, supervision, visualization, writing – review and editing.

Funding

Shahid Beheshti University of Medical Sciences.

Consent

Parents of the patient participated voluntarily and consented to the publication of clinical information related to their case. The study follows the principles outlined in the Declaration of Helsinki and is in accordance with the Ethical Code: IR.SBMU.REC.1398.059 and Clinical Trials code: IRCT20190826044620N1.

Conflicts of Interest

The authors declare no conflicts of interest.

Biazar E., Heidari‐Keshel S., Sadat Rezaee M., et al., “Acellular Fish Skin for Deep Dermal Traumatic Wounds Management: A Case Report,” Clinical Case Reports 13, no. 12 (2025): e71629, 10.1002/ccr3.71629.

Data Availability Statement

The data that support the findings of this study are available from the corresponding author upon reasonable request.