Standardised Algorithm for Peri‐ and Postoperative Wound Management Using Fish Skin Grafts and Octenidine in Head–Neck Surgery

ABSTRACT

Complex reconstructions are often required after head and neck tumour resections, particularly in irradiated fields and areas with exposed bone. Fish skin grafts (FSG) have recently emerged as a potential adjunct in difficult wound healing. This case report series evaluates the effectiveness of FSG in combination with octenidine‐based antiseptics, which have already shown beneficial results in split‐thickness skin transplantation in high‐risk patients, focusing on the time period for granulation and wound closure. Five patients with seven defects of different aetiology in the head and neck region received FSG applications. Defect sizes ranged from 2 × 4 cm (occipital) to 7 × 6 cm (temporal). Granulation was determined, with irradiated and non‐irradiated wounds analysed separately. In three consecutive cases, octenilin gel (octenidine‐based hydrogel) was implemented in the treatment regimen. Three patients achieved complete granulation, while two reached 66%–80% granulation. Non‐irradiated wounds demonstrated faster granulation (mean 16.5 days) compared to irradiated wounds (mean 48.8 days). Although there was no statistical significance, a trend toward delayed healing in irradiated tissue was observed. Patients treated with octenilin gel showed favourable healing outcomes, including shorter granulation times. Despite the poor prognosis for uncomplicated healing in this cohort, both treatment protocols—octenisept with Flaminal forte and octenisept with octenilin gel—achieved satisfactory outcomes when combined with FSG transplantation. This approach appears promising for reconstruction in challenging head and neck wounds and warrants further evaluation in prospective clinical studies.

1.

Summary.

• Fish skin grafts (FSG) support granulation and wound closure in complex head and neck defects.

• Both irradiated and non‐irradiated wounds benefited from FSG combined with octenidine‐based antiseptics.

• Non‐irradiated wounds showed markedly faster granulation (mean 16.5 days vs. 48.8 days).

• Use of octenilin gel was associated with improved healing dynamics.

• FSG with octenidine antisepsis represents a promising adjunct for reconstruction in high‐risk wounds.

2. Introduction

In tumour surgery, extensive resections can be necessary to completely remove tumours. Additionally, necessary radiation therapy can result in (chronic) wounds, making defect reconstruction challenging. Alongside functionality, aesthetic outcomes are also important considerations. If standard methods along the reconstructive ladder like primary closure, free skin grafts, local flaps and pedicled flaps are unsuitable, new methods must be considered. For split‐ or full‐thickness skin grafts for example, a vital wound ground is necessary. When the skull bone is exposed, these methods cannot be used and more complex reconstructions methods must be considered [1, 2]. The more complex the reconstruction, the higher the perioperative risk, which should be evaluated critically, especially in elderly patients with relevant comorbidities. One relatively recent method is the use of dermal skin matrixes [1].

There are several studies, that show promising results of using fish skin graft (FSG) in management of chronic wounds as a result of diabetes [3], chronic venous insufficiency, peripheral arterial occlusive disease [3] or burn wounds [4, 5]. Recently our group presented a successful case of using FSG on a parietooccipital irradiated chronic wound with an exposed external table of the skull after several operations due to a squamous cell carcinoma (SCC). Through FSG, it was possible to achieve granulation within one week and re‐epithelialization after full‐thickness‐skin (FTSG) implantation [6].

The FSG used in this case series is a medical device derived from the Atlantic cod. The decellularized, lyophilized sterile fish skin provides a dermal matrix, very similar to human skin, which enables the ingrowth of dermal−/stem cells and angiogenesis to support granulation (3,7–9). In contrast to xenografts derived from bovine or porcine sources, there is no known risk of viral disease transmission and a higher acceptance in patients and clinicians due to less cultural or religious burden [3, 7, 8].

The objective of this article is to assess the effectiveness of FSG in achieving granulation and re‐epithelialization in complex head and neck wound environments, particularly in pre‐radiated regions with exposed skull bone. To further improve our implemented treatment regimen, we used FSG for the first time together with octenidine based products. This antiseptic has already demonstrated superior outcomes for split‐thickness skin transplantation in high‐risk patients [9], as it not only prevents wound infections but also promotes vascularization [10].

3. Materials and Methods

3.1. Fish Skin Graft

FSGs have emerged as a promising innovation in wound care, offering unique advantages over traditional wound dressings and graft materials. In 2013, the United States Food and Drug Administration (FDA) approved a novel product, decellularized fish skin derived from the Atlantic cod ( Gadus morhua ) (Kerecis Omega3 Wound, Kerecis, Iceland). We used this medical device in the case series presented here. Unlike conventional options, such as porcine or bovine‐derived matrices, FSGs retain their native structure and composition, including essential natural omega‐3 fatty acids, without the need for antibiotics or virus‐inactivating methods [8].

3.2. Octenidine

For antiseptic treatment we used the medicinal product octenisept (0.1% octenidine, 2% phenoxyethanol; Schülke & Mayr, Germany) for wound disinfection and octenilin wound gel (octenidine, Hydroxyethylcellulose; Schülke & Mayr, Germany), a hydrogel to prevent FSG from dehydration. Both products contain the same well tolerated antiseptic active and are compatible with each other.

3.3. Wound Dressings & Suture Materials

Adaptic Touch Non‐Adhering Silicone Dressing (Systagenix Wound Management, Gargrave, UK) is a flexible, non‐adherent silicone wound contact layer used to protect wounds while minimising trauma during dressing changes. The dressing's low‐tack silicone design prevents adherence to the wound surface and allows atraumatic removal. Its open mesh structure supports fluid transfer to a secondary dressing, which reduces the risk of exudate pooling and subsequent maceration [11]. 5–0 Monocryl suture was used for suturing. To ensure contact between the graft and the wound area a mattress suture with absorbable suture material was performed (4–0 Vicryl).

3.4. Patients

We describe seven defects on five patients (one male, 4 female), 58–92 years of age with squamous cell carcinoma (SCC), basal cell carcinoma (BCC) or post radiogenic chronic dermatitis as primary disease and therefore with indication for FSG. Two patients were treated with FSG using conventional protocol, for the others FSG was used in combination with an octendine‐based hydrogel. Detailed demographics, wound aetiology, treatment locations, history of radiation, and outcomes are demonstrated in Table 1. All patients gave their written and informed consent and the case series was registered under researchregistry.org under UIN:researchregistry10815.

TABLE 1.

Patient characteristics.

Patient	Sex/age (y)	Primary disease	Localisation	Defect size (cm)	Number of Pre‐operations in the field	Pre‐radiation	Intact Periost	Hydrogel	Number of treatments with FSG	Granulation	Granulation time (d)	Additional full‐thickness skin graft
1	F/76	SCC T3N0M0	Occipital	4 × 5	1	Yes	No	Fl	1	100%	7	Yes
2	M/58	post radiogenic chronic dermatitis	Occipital	2 × 4	2	Yes	No	Fl	2	80%	63	Yes
			Parietooccipital	6 × 5	2	Yes	No	Fl	2	80%	63	Yes
			Parietooccipital	6 × 6	2	Yes	No	Fl	2	80%	63	Yes
3	F/86	BCC EADO IIA	Frontal	6 × 4	1	No	Yes	O	1	100%	5	No
4	F/92	SCC T3N0M0	Temporal	7 × 6	2	No	No	O	2	100%	28	Yes
5	F/75	SCC T2N0M0	Temporal	6 × 5	8	Yes	No	O	3	66%	48	Yes

Abbreviations: BCC: basal cell carcinoma; F: female; Fl: flaminal wound gel; FSG: fish skin graft; n/a: not applicable; M: male; O: octenilin wound gel; SCC: squamous cell carcinoma.

3.5. Treatment Protocol

Depending on the underlying pathology, our regimen is based on following algorithm in Figure 1 and additionally depicted in Figure 2 showing the preparation of wound area and grafting as well as the intraoperative procedure for one representative patient.

FIGURE 1.

FSG treatment algorithm.

FIGURE 2.

Intraoperative algorithm in exposed skull from resection to disinfection to abrasion of an FSG implant (A–D). (A) chronic post‐radiogenic dermatitis, (B) after resection, abrasion of external table and disinfection, (C) FSG implantation and suturing with Monocryl 5–0, (D) final intraoperative result.

3.5.1. Exposed Skull

First, necrotic tissue is resected, wound edges are freshened, and the external table is abraded extensively to the point of induced bleeding. To reduce possible bacterial colonisation, the wound and surrounding skin is disinfected using the antiseptic solution. The FSG is then prepared, which means adapted according to the wound size and soaked in physiological saline solution for 3 min before it is meshed or punctured. 5–0 Monocryl suture is used for suing. The graft must be in contact with the wound ground, a plane relief must be achieved by drilling the external table. Afterwards, a moist environment is created using a hydrogel. The non‐adherent wound dressing and a saline‐soaked gauze are applied, followed by a compress dressing.

3.5.2. Postoperative Treatment

During the first week, dressing change is performed daily, according to the intraoperative protocol consisting of the hydrogel, a non‐adherent wound dressing, a saline‐soaked gauze on top which is finally fixed with a compress dressing. In the following week, the entire dressing is changed every two to five days. Two weeks after the transplantation, the wound is evaluated by the surgeon to determine if granulation tissue formation is adequate for secondary wound healing or, due to insufficient granulation, either another FSG is needed or full‐thickness skin graft can be transplanted.

Hydration and sterility of the recipient site is important throughout the whole period, in order to prevent graft loss due to dehydration or infection. These specifications are guaranteed by using both octenidine containing products.

3.6. Statistics

Influence of pre‐radiation on outcome and time to granulation is analysed by performing Mann–Whitney U test.

4. Results

The included patients presented chronic wounds due to following primary diagnoses: three cases of squamous cell carcinoma (SCC), one case of basal cell carcinoma (BCC), and three defects (in one patient) due to post‐radiogenic chronic dermatitis following complex BCC treatment. The locations were as following: two cases in the parietooccipital region, two in the occipital region, two in the temporal region and one in the frontal region. The size of defects varied from 2 × 4 to 4 × 5 cm in the occipital region, 6 × 5 to 6 × 6 cm in the parietooccipital region, 6 × 4 cm in the frontal region to 6 × 5 to 7 × 6 cm in the temporal region, respectively. All patients already underwent surgeries in the affected field prior to the here described protocol, with three even multiple procedures. Pre‐radiation therapy was performed on three patients. Needed FSG treatments ranged from one to three applications across patients. Granulation levels varied, with three patients who achieved 100% and two achieved at least 66%–80% within 48–63 days. Four patients required additional full‐thickness‐skin grafts (FTSG), that is, demonstrated in Figure 3 with Flaminal and Figure 4 using octenilin gel, whereas re‐epithelization was achieved in one case (unsing octenilin gel) without FTSG transplantation. To evaluate any possible additional advantages in a first case series, we modified our current regimen by using the octenidine‐based hydrogel in three consecutive patients.

FIGURE 3.

Patient #1 without periost (intraoperatively A–C), presented full granulation after 7 days (D), received FSTG transplant (E) condition three months post‐surgery and (F) one year postoperative [6].

FIGURE 4.

Patient #4 with full granulation after 28 days and epithelisation after FTSG after 32 days (A‐F). (A) temporal T3 SCC, (B) intraoperative after resection, (C) failure of first FSG due to a lack of hydrogel, (D) full granulation after second FSG after 28 days, (E) preoperative before FTSG implantation, (F) 32 days after second FSG transplantation and 4 days after FTSG implantation.

In Table 1 we summarise both the patients' anamnesis and treatment procedures as well as the follow up after FSG transplantation.

Patients who underwent radiation therapy experienced longer granulation times up to 63 days, achieved lower levels of granulation (66%–80%) and required all additional FTSG transplantation.

Otherwise, in the here studied non‐irradiated patients, time to granulation was typically faster, ranging from 5 to 28 days. The fastest time until full granulation within only 5 days was observed in a non‐irradiated patient with intact periosteum, treated additionally with octenilin gel. Although all presented individuals were associated with poor prognosis for uncomplicated wound healing, both protocols—octenisept and Flaminal forte or octenisept and octenilin gel—achieved highly satisfying results when combined with FSG transplantation.

An exploratory comparison between irradiated (n = 5, mean = 48.8 days) and non‐irradiated (n = 2, median = 16.5 days) tissues indicates longer healing times in irradiated wounds. Due to the very small sample size, no statistically significant difference could be demonstrated (p > 0.05).

4.1. Qualitative Observations

Photographic documentation demonstrated that wound bed conditions improved significantly following FSG application. Patients treated with octenilin gel showed favourable healing outcomes, including quicker granulation time, suggesting that octenidine may play a role in optimising the wound environment and reducing the need for secondary procedures. Exemplified for one patient in Figure 5.

FIGURE 5.

Patient #3 defect after FSTG failure and following FSG implantation with intact periost and consecutive full epithelization without contracture after 6 weeks in follow‐up (A‐E). (A): Intraoperatively prior to FSG implantation, (B) intraoperatively after FSG implantation, (C) 18 days after FSG implantation, (D) day 28, (E) 6 weeks postoperative without contracture and full epithelisation.

5. Discussion

Our case series provides insights into the effectiveness of fish skin graft (FSG) transplantation combined with octenidine‐based wound management in complex and chronic wounds in the head and neck region. We observed notable differences in wound healing outcomes between irradiated and non‐irradiated tissues, with additional observations suggesting that the type of antiseptic regimen could influence granulation time and healing quality.

Since FSG is a new therapeutic option, there are no standardised or established treatment protocols regarding peri‐ and postoperative management available. Current studies primarily aim to assess the effectiveness of FSG rather than to develop an optimal treatment algorithm, and the methodology is often insufficiently described in literature. Variations, particularly in perioperative treatment, are therefore likely, making the outcome of different publications difficult to compare. Until now, particularly in the head and neck region, the use of FSG remains largely unexplored. Most experience for therapeutic advances with FSG has been gained in the treatment of chronic venous or diabetic ulcers [12, 13, 14, 15].

Tickner et al. recently provided general recommendations for FSG, based on expert consensus. They emphasise adequate wound bed preparation through specific debridement, avoiding graft application on untreated infections, and ensuring graft hydration with saline for optimal wound contact. FSG should be meshed to prevent seroma, fixed in place, and covered with a non‐adherent dressing, with weekly outpatient evaluations recommended. Furthermore, these authors suggest FSG as bridge therapy for more complex wounds, while smaller wounds may heal using only FSG. FSG is also effective for wounds with exposed bone, and negative pressure wound therapy (75–125 mmHg) is considered beneficial, even though it can be problematic in the head and neck region [16].

Dorweiler et al.'s multicenter report illustrates the lack of standardised protocols for FSG transplantation across hospitals. After initial debridement, FSG was used and protected with foam dressings or the additional application of negative pressure therapy. Dressing changes varied from 2–3 days to weekly. Promising results were reported, however with a wide range of matrices applied per patient [17]. Similarly, Kim et al. used absorptive foam dressings on the FSG, but further details on the protocol were not provided [5].

This variation in protocols and lack of detailed reporting makes it challenging to assess the effectiveness of specific FSG steps of treatment. The integration of an octenidine‐based hydrogel in the wound regimen yielded promising results as patients showed increased level of granulation and a reduced risk for another FSG procedure.

In the discipline of head and neck surgery, FSG is still uncommon, but Wang et al. [18] recently documented its use for periocular reconstruction after tumour excision in six patients. Parts of their procedure—freshening wound edges, meshing the FSG and soaked in saline, suturing the graft—parallels our approach. In contrast, they used FSG for deep defects, securing them with a bolster for two weeks and prescribed the antibiotic erythromycin used as ointment for a month to protect the graft from infection. The authors found that FSG is an effective option for functional and cosmetic outcomes in this area. Even though not statistically significant our results indicate that non‐irradiated wounds are associated with shortened time to granulation, [19] an effect that was further improved when adding octenidine to the regimen. Beyond antiseptic efficacy, this molecule was recently associated with additional characteristics, like anti‐inflammatory effects and a positive influence on matrix metalloproteinases (MMPs), both important factors especially in treatment of hard to heal wounds [20, 21].

Although our observations indicate that FSG combined with octenidine‐based wound management may support granulation and wound healing in complex head and neck defects, these findings must be interpreted with caution as the present work is limited to a small case series, which limits generalizability. Furthermore, differences between irradiated and non‐irradiated wounds or between antiseptic regimens cannot be considered as a proof of superiority.

Nevertheless, in context with FSG, another interesting aspect is the low level of wound contracture in secondary healing, which could be a relevant secondary end point in other studies and exploring advanced wound assessment tools could be valuable. We aim to evaluate the different phases of healing in FSG‐treated wounds using hyperspectral imaging analysis in an upcoming project, which may provide more objective insights into wound perfusion and progress of granulation. This approach could be useful for more tailored and responsive treatment strategies in the future, but future prospective clinical trials with larger patient cohorts, standardised protocols, and comparative designs are therefore necessary to confirm these preliminary findings and to clarify the specific role of octenidine and fish skin grafts in complex head and neck reconstruction, as lack of a control group was also a limitation of the presented first case series.

6. Conclusions

In line with findings from Veitinger et al. from our study group and Wang et al., our case series demonstrates promising results for using FSG in head and neck reconstruction. Some experts already propose to update the traditional reconstructive ladder and to include dermal matrices as an option before considering free or local flaps [1].

Our case series presents a novel treatment protocol including a modern antiseptic molecule for wound bed preparation. Octenidine seems to support granulation and reduces additionally needed interventions in non‐irradiated patients.

Ethics Statement

The case series, titled “Fischhaut als rekonstruktive Möglichkeit in der Kopf‐Hals‐Chirurgie,” was conducted in accordance with the Declaration of Helsinki, registered under researchregistry10815 within researchregistry.org, and approved by the Ethics Committee of the Medical Faculty of Heidelberg University (Ethikkommission der Med. Fakultät, Heidelberg). The protocol was reviewed and approved on January 7, 2025, under the approval number S‐806/2024, with no objections to its implementation.

Consent

Participation in this case series was voluntary and patient gave written consent prior treatment. A potential human face in one image is included in this manuscript. Consent for publication was obtained from the respective individual in German institutional consent form.

Conflicts of Interest

The main author, L.S.F., serves as an external expert for Kerecis, the producer of the fish skin grafts used in this case series. However, this connection has no influence on the objectivity of the results, as the case series followed a standardised algorithm for peri‐ and postoperative wound management using fish skin grafts and octenidine in head–neck surgery. Additionally, C.K. is affiliated with Schülke & Mayr, the producer of octenidine. Despite this affiliation, C.K. declares that this has no influence on his objectivity or the integrity of the case series findings. The further authors declare no conflicts of interest.

Fiedler L. S., Lippert B. M., Klaus C., Plath M., and Zweigart G., “Standardised Algorithm for Peri‐ and Postoperative Wound Management Using Fish Skin Grafts and Octenidine in Head–Neck Surgery,” International Wound Journal 22, no. 11 (2025): e70775, 10.1111/iwj.70775.

Data Availability Statement

All relevant data generated or analysed during this case series are included in this published article. Additional data may be available upon reasonable request from the corresponding author.