The marine Omega3 wound matrix for treatment of complicated wounds

A total of eight patients were treated between November 2014 and April 2017 in this extension of the authors’ initial pilot series [16]; the inclusion criterion was a complicated wound on the lower limb following previous amputation with exposed bone and a risk of reamputation (proximalization). The average age of patients was 71 ± 8 years (Table 1) and all patients had at least two risk factors for cardiovascular disease.

Sufficient peripheral perfusion was initially achieved surgically in six of the eight patients by placing a popliteopedal (n = 5) or femorocrural bypass (n = 1); however, bypass occlusion occurred in one patient that required firstly lower and then upper limb amputation following unsuccessful thrombectomy. Of the patients two had primarily adequate peripheral perfusion. Thus, all patients exhibited adequate arterial perfusion in the wound area at the start of treatment (ankle-brachial index ABI > 0.5 and/or transcutaneous partial pressure of oxygen [tcpO₂] > 40 mm Hg). Reamputation and proximalization of the amputation level was performed in 6 (Chopart amputation n = 2, proximal transmetatarsal amputation n = 3, transmetatarsal amputation n = 1) of 8 patients due to impaired wound healing in the wound area following initial amputation: one patient [1] had already undergone secondary resection twice (distal bone, proximal bone). Therefore, all seven patients with impaired wound healing and partially exposed bony segments were at risk of conversion to major amputation (n = 6) or hip disarticulation.

Initial wound treatment comprised radical surgical debridement, with swabs taken intraoperatively under aseptic conditions. The Omega3 wound matrix was then cut according to wound size, soaked in physiological saline solution for 1 min, and then applied to the wound and covered using a silicone foam dressing (Mepilex® Border, Mölnlycke Health Care, Göteborg, Sweden). In the further course, wound treatment was continued in the outpatient setting with one visit per week. At each visit, the wound was cleaned or debrided, wound size was photodocumented, and any defects/zones of patch absorption filled with new Omega3 wound matrix.

The statistical analysis of patient data and the quantification of wound surface area were carried out using MS EXCEL (Microsoft Corp., Redmond, WA, USA) and Fiji/Image J open source software (imagej.nih.gov/ij/), respectively.

Altogether, 10 wounds in 8 patients were treated in the region of the forefoot (n = 8, Fig. 2) and the proximal thigh (n = 2). The average wound size was 23 ± 18 cm² (range 6–63 cm²) and the time to complete wound healing 23 ± 10 weeks (9–41 weeks) on average. To achieve this, a total of 133 Omega3 wound matrices (size 3 × 7 cm) were used (median 17 [7–26] patches/patient).

Based on an evaluation of the photodocumentation, it was possible to also graphically show the kinetics of wound healing for each of the first seven wounds in this study. To improve interpretability, individual wound sizes (baseline surface area = 100%) and the respective time to healing (time of complete healing = 100%) were normalized and presented in the form of a wound-specific healing curve (Fig. 3a). From the resulting dot matrix, a common polynomial trendline was then determined for all curves in a second step (formula: y = −0.0001x³ + 0.034x² − 2.8576x + 92.879, Fig. 3b). This non-linear trendline clearly shows that a 50% reduction in wound area could be seen as early on as after 20% of the treatment duration.

Intraoperative swab taking showed colonization with one type of bacteria in five cases (Escherichia coli, extended spectrum beta-lactamase-positive E. coli, Streptococcus agalactiae, Enterobacter cloacae, and Staphylococcus aureus) and multiple colonization in three cases (S. agalactiae/Klebsiella oxytoca/Staph. aureus and Pseudomonas aeruginosa/Enterobacter cloacae, E. cloacae/E. coli/Enterococcus species). All patients received targeted antibiotic therapy, with three patients having completed this by the time of discharge, while oral antibiotic therapy was continued in two patients until complete wound healing. An additional effect was observed for the Omega3 wound matrix in that a reduction in pain levels and analgesic use was seen over the course of treatment in all patients on analgesic therapy (wound pain despite DFS). In patient 1 in particular, the (initially high) dose of opioids could be discontinued after 1 week of treatment.

The acellular dermal matrix derived from fish skin (Omega3 wound matrix, Kerecis) was used to treat wounds in 10 patients (10 vascular wounds) between 2015 and 2017 (Table 1). Of the patients eight had peripheral arterial occlusive disease (PAOD) Fontaine stage IV and concomitant DFS, one female patient had extensive vasculitis (MPO [myeloperoxidase], p‑ANCA, cryo-positive) of small, medium, and large vessels in the setting of undifferentiated collagenosis. Ultimately, emergency below-the-knee amputation of both legs was necessary due to advanced gangrene infections. This patient suffered from a persistent wound on the lower leg stump. Another female patient had combined PAOD and small-cell vasculitis in addition to metastatic cancer. Of the patients six had previously undergone endovascular recanalization, while two patients had undergone a pedal bypass. Early occlusion occurred in one patient following bypass surgery, whereby limb preservation was nevertheless possible. Of the patients one had undergone forefoot amputation following revascularization, while ray resections were performed in two cases. A mediasclerotic ABI > 1 was detected in five patients prior to treatment initiation with the Omega3 wound matrix, and the ABI following pedal bypass was 0.87 in one patient and 0.57 in another patient. The ABI in the patient with early graft occlusion was >0.4. At 2–26 months following revascularization, wound healing was absent in all patients despite modern wound treatment with hydroactive wound materials. Wound size varied between 3 cm² and 57.7 cm². No infections were present at the time of (and during) treatment and no patients received antibiotics at the time of treatment. Following thorough wound debridement, the fish-skin matrix that had been cut to the right size (3 × 3.5 cm or 3 × 7 cm, depending on wound size) and soaked in 0.9% saline solution was adapted to the wound size (Fig. 4). The wound was then covered with a polyurethane foam dressing (Biatain Silicone, Coloplast, Humblebæk, Denmark). This dressing was changed at intervals of 2–3 days while leaving the fish-skin matrix in place. Patients underwent treatment every week up to a maximum of nine fish-skin applications. The female patient with early graft occlusion was an exception and to date, she has undergone 17 applications over 12 months after initial treatment success was followed by Pseudomonas colonization and subsequent wound enlargement and it became necessary to discontinue Omega3 wound matrix therapy. Following local eradication, treatment with the Omega3 wound matrix was resumed and is currently ongoing. All wounds were photodocumented and measured two-dimensionally. The statistical analysis of patient data and the quantification of wound surface area were carried out using MS EXCEL (Microsoft Corp.) and Fiji/Image J open source software (imagej.nih.gov/ij/), respectively.

The matrix was completely absorbed within 7 days. It was possible to achieve wound healing in 50% of patients (n = 5) within 4 months (60–160 days). The remaining wounds exhibited wound reduction rates of 19–79% within the first 3 months (21–84 days) following treatment initiation (Fig. 5). The largest wound (57.7 cm², present for 25 months prior to treatment initiation) showed a wound reduction rate of 19% within 49 days. In the patient with early pedal bypass occlusion and intermediate wound enlargement following Pseudomonas colonization, a wound reduction rate of 67.9% (maximum wound size 46.8 cm², current wound size 15.05 cm²) has been achieved to date. No infections or immune reactions occurred during the treatment period. Pseudomonas colonization was treated by drying out the wound with a superabsorber (Sorbion Sachet, BSN, Hamburg, Germany) and discontinuing Omega3 wound matrix therapy (Table 1).

The use of the Omega3 wound matrix at the Karlsruhe Hospital is reserved for complicated chronic wounds with a certain level of non-reactivity. Efficient exudate and infection control is the first prerequisite of successful application. The fish-skin matrix is preferably applied under sterile conditions in the operating theater following debridement and covered with a polyurethane foam or negative-pressure wound therapy (NPWT); this may need to be repeated several times at weekly intervals. As part of the assimilation process, harmless discoloration and shrinkage of the matrix can be seen after a few days; however, contact with the wound results in improved fibroblast activity and early granulation and if conditioning is successful within the right time window, a mesh graft can be helpful at the end of the process to achieve definitive wound closure.

The matrix has been used highly selectively in only five patients as yet (Table 1) where three of the wounds were on lower limbs and two wounds were on the hand: o hand was treated following borderline amputation due to catecholamine therapy and concomitant radial artery occlusion. The patient, who was multimorbid (liver cirrhosis, chronic myelofibrosis, thromboangiitis, among other disorders), had undergone multiple urological surgical procedures due to perineal Fournier’s gangrene and required intensive care for a prolonged period of time (sepsis, hemofiltration). It was possible to achieve almost complete healing of the wound on the hand (Fig. 6). Another case of use on the hand involved necrosis formation in (protracted) pronounced steal syndrome despite banding of the shunt in dialysis-dependent patients. Of the lower limb wounds two involved persistent, infected lower leg venous ulcers, one of which was an infected mixed ulcer (initially 20 × 15 × 1 cm; W × L × D) accompanied by formation of a deep soft tissue pocket and extensive abscess channel formation in the muscles of a 66-year-old patient with severe postthrombotic syndrome following two instances of deep vein thrombosis and concomitant PAOD. The matrix achieved granulation and healing of the channel (Fig. 7), while the Omega3 wound matrix, an autologous P1 vein bypass, multiple debridement with fasciectomy, and consistent compression therapy were able to condition the ulcer for a mesh graft and achieve its healing. Unfortunately, ulcer recurrence due to insufficient compression and restenosis in the vein bypass were seen at 1‑year follow-up.

In this way, it was possible to achieve complete healing in three patients and stable wound conditions in two patients, one of which (following steal syndrome of the hand) is still under treatment due to poor patient compliance.

Digital photodocumentation was carried out for the reported patients over the course of the inpatient stay; following transfer to an outpatient wound network, photodocumentation was performed using the AKESTES © system (Akestes, Berlin, Germany; [17]). This system enables clinical data collection and area determination by means of pixel marking of the wound area. Thus, the authors’ early experience supports the use of the matrix not only in hard to heal ulcers, but also in persistent cavities on the lower leg and upper limbs.