Management of Open Distal Lower Extremity Wounds With Exposed Tendons Using Porcine Urinary Bladder Matrix

The ultimate goal of lower extremity limb reconstruction for wounds with exposed tendons is obtaining wound coverage that is stable and durable with normal tendon gliding and associated joint mobility. Ideally the patient should have a pain-free, normal-appearing leg and foot that can fit into regular footwear. The use of pedicle or free flaps in the management of these patients is frequently suggested as the optimal means of wound closure.^1-10 However, the additional bulk of flaps to the foot and ankle region often limits the use of normal footwear and requires future revisions. A collagen-glycosaminoglycan biodegradable matrix (Integra Bilayer Wound Matrix, Integra LifeSciences Corp, Plainsboro, NJ) has been reportedly used in managing wounds with exposed tendons.^11-18 Utilizing negative pressure wound therapy (NPWT) with or without future skin grafting is helpful in managing patients with these wounds,¹⁹ but marked scarring and graft adherence can develop.²⁰ Thus, the authors began utilizing newer extracellular matrix (ECM) treatment methods for the management of complex full-thickness wounds including exposed tendon in challenging flap candidate patients. This report summarizes the authors’ experience utilizing porcine urinary bladder matrix ECM (UBM-ECM) products in the management of challenging distal lower extremity wounds with exposed tendons

With Institutional Review Board approval, from February 2012 through April 2014, a total of 13 patients with foot or lower third extremity wounds involving tendons were managed by the Plastic Surgery Service at St. Louis University (St. Louis, MO) utilizing porcine urinary bladder matrix-extracellular matrix (UBM-ECM) (MicroMatrix, MatriStem Multilayer Wound Matrix, and MatriStem Surgical Matrix RS, PSM, and PSMX, ACell Inc, Columbia, MD) as the primary wound management modality. At the time of initial plastic surgery evaluation, these patients were not deemed suitable candidates for routine surgical management with standard local or free flap techniques; therefore, none of these patients had a flap procedure. Multiple medical comorbidities and an inability to undergo extensive surgical procedures were the primary reasons for alternative wound management. The medical comorbidities were as follows: culture positive wounds 77% (10/13); diabetes mellitus 38% (5/13); smoking 31% (4/13); leg edema/venous stasis 23% (3/13); and a body mass index greater than 35 15% (2/13). Additional medical problems included 1 patient each with end-stage renal disease on hemodialysis, congestive heart failure, coronary artery disease with prior myocardial infarction, and active atrial fibrillation on anticoagulation. One patient with an Achilles tendon wound was on immunosuppression for a prior pancreas and kidney transplant.

There were 6 open Achilles tendon wounds, 6 open tibialis anterior tendon wounds, and 1 peroneus longus and brevis tendon wound. The time of initial UBM-ECM treatment relative to the date of injury varied depending upon when the patient was referred and when the patient agreed to comply with the treatment regimen (no cigarette smoking and limited tendon motion with foot and ankle immobilization). All patients received parenteral prophylactic antibiotics preoperatively, and appropriate oral antibiotics were given as indicated by the wound bed cultures at the time of debridement and product placement (Table 1). These antibiotics were continued until the wound had healed to the point that the tendons were no longer exposed. Only 1 of the 4 patients who smoked maintained a nonsmoking status during treatment and during the follow-up period. 

The treatment protocol involved judicious excisional debridement of the wound bed and tendon with scalpel, scissors, or hydrosurgical debridement (Versajet Hydrosurgery System, Smith & Nephew, Hull, UK). All intratendinous sutures were also removed to rid the wound of foreign material. All wounds received a topical application of UBM-ECM micronized powder (MicroMatrix) to the wound bed, tendons, and remaining interstices. Earlier patients in the study had 2-, 3-, or 6-layer vacuum-pressed UBM-ECM sheets (MatriStem Surgical Matrix) used while later study patients also had the 2-layer lyophilized UBM-ECM multilayer sheets (MatriStem Multilayer Wound Matrix) applied in place of or along with the vacuum-pressed sheets. Experience led to placement of more UBM-ECM product into the wound at the time of the initial surgery in the patients treated later in the study. The product was placed into the wound to fill it to skin level and, when possible, attempts were made to close the wound over the product. In all cases, the product was retained in the wound with sutures or staples and a polyurethane sheet dressing (Tegaderm, 3M, St. Paul, MN) placed over the wound to keep the product moist. After the UBM-ECM product placement, subsequent wound care was determined by the amount of wound drainage and the need to keep the tendon moist. Concomitant treatments included negative pressure wound therapy (NPWT) (for drainage over 20–50 cc/day), hydrogels, petroleum gauze, and additional polyurethane sheet covering. An absorptive pad outer dressing was then changed as needed for the draining fluid. Unlike standard moist wound therapy treatment, the wounds treated with UBM-ECM performed well in a more moist environment and needed less frequent dressing and wound manipulation. Earlier study patients were observed in the clinic more frequently due to concerns about potential complications, but as the authors’ experience increased, the patients treated later in the study were observed less frequently. Patients with an open Achilles tendon wound had their active tendon excursion limited by external pin fixation systems, ankle immobilizers, or healing Ankle Foot Orthosis (AFO) boots as fitted by an orthotic specialist. Other patients simply needed posterior ankle splint immobilization.  If primary skin closure was not possible, patients with larger wounds received a partial- or full-thickness skin graft to close the wound once the wound volume was filled and completely vascularized. The patient clinical data and care is summarized in Table 1 and Table 2. 

The number of applications of UBM-ECM by tendon group was as follows: tibialis anterior tendon wounds: 1-2 (average 1.2, median 1) (Figure 1); Achilles tendon wounds: 1-3 (average 1.83, median 2) (Figure 2, Figure 3); and peroneal longus and brevis tendons wound 7 treatments (Figure 4). The treatment of the one patient with the largest complex open ankle joint with multiple exposed tendons that received 7 treatments (separated out from the tibialis anterior tendon group above) is shown in Figure 5. Primary skin closure was attempted in 4 wounds involving the Achilles tendon and in 1 wound involving the peroneal tendons. Split- or full-thickness skin grafts were used to achieve complete wound closure in 2 wounds involving the Achilles tendon and 4 wounds involving the tibialis anterior tendon. Smaller wounds involving the tibialis anterior tendon closed with no need for skin grafting. The average follow-up was 20 months with a minimal follow-up of 13 months.

The time from initial UBM-ECM product application to wound closure varied from 6–78 weeks, with the larger wounds requiring more time to heal. All wounds achieved closure despite a variety of positive cultures at the time of initial UBM-ECM application. In the exposed Achilles tendon wound group, healing times ranged from 7–78 weeks, with an average of 33 weeks to complete wound healing (median 28 weeks). In the exposed tibialis anterior tendon group, healing was achieved by 6–18 weeks (average 11 weeks; median 9 weeks). The 1 peroneal tendon exposed wound closed in 14 weeks. Time to skin graft application after initial UBM-ECM product application ranged from 3.5–16 weeks overall (average 10.3 weeks; median 10.5 weeks). Two of 6 (33%) Achilles wounds were ultimately grafted at 5 and 16 weeks after UBM-ECM application. Three of 5 (60%) exposed tibialis anterior tendon wounds were grafted, 3.5–15 weeks after initial UBM-ECM product application (average 7.8 weeks; median 5 weeks). One patient with a posterior Achilles wound and bilateral venous stasis disease redeveloped a small wound during a leg ulcer flare that subsequently healed with compression and topical care.

A majority of patients had multiple treatments (7/13) of UBM-ECM, with most of these secondary product applications occurring in the clinic (Figure 1, Figure 2, Figure 3, Figure 4). A notable exception was 1 of the patients treated early in the study who had a severe wound involving an open ankle joint with loss of all anterior ankle tissues except for the tendons, and whose wound required multiple product applications in the operating room (Figure 5). Time to ambulation from initial UBM-ECM application was 8–33 weeks in the exposed Achilles wound group (average 20 weeks; median 21 weeks) and 7–17 weeks (average 11.4 weeks; median 10 weeks) in the exposed tibialis anterior tendon group. The patient with the exposed peroneal tendons was poorly compliant and ambulated throughout his postoperative treatment. No significant skin graft losses were noted, and all wounds were considered healed approximately 3 weeks after skin grafting.

The UBM-ECM products appeared to perform well in an environment kept more moist than typically employed in classic moist wound therapy regimens. Therefore, the authors transitioned from more frequent NPWT use in patients treated earlier in the study to its seldom-prolonged use in the patients treated later (after the first study year) in the study. The authors found a simple polyurethane sheet or a foam gauze dressing with daily application of several milliliters of saline or hydrogel on the wound typically provided an appropriate amount of moisture. With larger wounds, 1 to 2 layers of a Drawtex (SteadMed, Fort Worth, TX) dressing was added over an Adaptic (Johnson & Johnson, New Brunswick, NJ), nonadherent layer to achieve a better moisture balance under the polyurethane sheets. These dressings were then changed every 2–3 weeks in the office, when additional products could also be added. The patient changed an outer absorptive dressing as needed in the management of any fluid leakage that occurred from under the polyurethane sheets.

In 4 wounds involving the Achilles tendon and the 1 wound involving the peroneal tendon, wound dehiscence was observed after closure due to postoperative swelling or the patient ambulating against advice. Wound dehiscence did not lead to loss of product or compromise healing. The wound separation was managed by the application of a topical moist dressing. Of note, the hydrated UBM-ECM product can have the appearance of standard wound slough and should be carefully retained in the wound as its presence facilitates the ongoing tissue remodeling process.

This retrospective study showed UBM-ECM products can facilitate wound healing in open, traumatic, lower extremity wounds involving exposed tendon and positive cultures. All treated wounds showed satisfactory filling of the tissue deficit around the exposed tendons. Wound closure was observed in all patients with either primary reepithelialization, development of granulation tissue to support a skin graft, or primary reapproximation of the wound margins. Wounds managed with UBM-ECM had a noticeable decrease in periwound edema and drainage similar to wounds managed with NPWT. Wounds that had positive bacterial cultures but were not grossly infected responded well to UBM-ECM wound therapy. Patients reported reduced pain and accepted the more prolonged time course of the UBM-ECM wound healing process. The healed wounds have fairly normal appearance and allow the patients to wear regular footwear and ambulate without assistive devices. After achieving wound closure, patients had minimally associated wound pain and no patient required medications for chronic pain.

The challenges in managing lower extremity wounds with exposed tendons include frequent tendon desiccation, marked peritenon inflammation, and drainage induced by tendon motion. Given these obstacles to healing, a wide variety of tendon wound treatments have been attempted.^1-10,15-17 The use of the collagen-glycosaminoglycan biodegradable matrix in managing open wounds with exposed tendons has shown great promise as it may allow coverage of a wound that otherwise would not have supported a skin graft.^18,20-24 Its use, however, requires a noninfected wound bed and at least a 2-stage procedure requiring secondary skin grafting. A recent review of free-tissue reconstructions of open wounds with exposed Achilles tendons advocated for anterolateral thigh flap reconstruction due to the limited success with other means of reconstruction of these wounds.¹⁴ Other authors¹⁶ have supported the use of local flaps in the absence of significant vascular disease for wounds up to 2.5 cm x 2.5 cm, while some¹⁷ have tried autologous dermal grafting with vacuum-assisted closure of 4 cm x 4 cm and more shallow wounds. In contrast, UBM-ECM products, which contain an exposed epithelial basement membrane layer, facilitate peripheral reepithelialization so that secondary grafting of smaller wounds is not needed. An in-depth study²⁵ of these wound devices via advanced mass spectrometry methodology showed 129 distinct proteins comprise the product. The healing effect is the result of all these proteins interacting with the wound bed.

For larger wounds, the intrinsic blood supply of the tendon is initially unable to support a skin graft. After UBM-ECM placement and tendon immobilization, enhanced healing of the wound bed is noted as more exuberant granulation begins forming that subsequently engulfs the tendon and allows secondary skin grafting on a newly, constructively remodeled tissue base and tendon. 

The UBM-ECM products are available in several formulations: a micronized powder, a lyophilized single to multilayer sheet, or a multilaminate vacuum-pressed sheet of varying thicknesses. These products are tissue-derived scaffolds with a complex biochemical composition that have not been fully characterized, but include collagens, glycosaminoglycans, and growth factors.^11-14 The micronized powder tends to remain in the wound for the shortest period of time as the body rapidly integrates the product. The lyophilized multilayer sheet remains in the wound bed for a longer duration, while the vacuum-pressed sheet takes the longest period of time to fully remodel into the wound bed. The UBM-ECM product has shown efficacy in both acute and chronic wound healing by facilitating the body’s ability to produce site-specific, constructively remodeled tissue.^11-14

This product use requires an appreciation of the differences in the appearance of the wound and wound bed. As the matrix constructively remodels the wound, it becomes incorporated into the healing wound surface and may have the appearance of wound slough or adherent exudate. Classical wound management experience would suggest this apparent wound slough or adherent exudate should be removed as it will limit wound bed granulation formation and promote bacterial colonization. The authors’ experience shows the desired adherent matrix that builds up with UBM-ECM therapy facilitates the formation of an exuberant, firm, healthy, vascular granulation tissue. It is important that ancillary care providers appreciate that these wounds do not need debridement but instead need to be kept moist and undisturbed.

The management of wounds with UBM-ECM has proven to be less complex than traditional wound care or long-term NPWT. The authors recommend product application as soon after the injury as feasible, since wounds tend to respond more favorably the earlier they receive treatment with UBM-ECM products. In the early management period when there is more copious drainage, NPWT is often employed. After 1-3 weeks when the amount of drainage decreases, alternative management regimens can be designed to allow for simple daily home wound care. With layered UBM-ECM products on the wound bed and a moisture-retentive primary dressing, the patient experiences much less wound care pain, because the actual wound bed can be left untouched for several weeks at a time. The periodic addition of moisture to the wound via hydrogel or tubing placed into the dressing is easily performed and well tolerated. When concerns about infection arise, silver releasing dressings such as an antimicrobial barrier silver dressing (Acticoat, Smith & Nephew, Hull, UK) or silver-plated nylon technology dressing (Silverlon, Argentum Medical, Geneva, IL) have been added to the topical dressing layer with success. An ongoing remodeling and softening of the wound is noted with progressive skin mobility after final closure. When healed, the normal appearance and contour of the leg allows for more optimal edema control.

Additional benefits of this wound management method include shortened physician operative time and postoperative care requirements so patients with these wounds can be easily added into an already busy surgical schedule. The total cost of care is potentially decreased by a greater ability for these wounds to be cared for at home or at a stepdown facility with monitoring of wound progress in the clinic every second to third week, instead of complex inpatient hospital care.

 A criticism of the present series is the time required to achieve wound closure, which was more prolonged than traditional pedicle or free-flap procedures or similar to that achievable with NPWT alone. However, the use of UBM-ECM avoids donor site morbidity and surgical complexity associated with traditional flap therapy, and it is less cumbersome than NPWT. The ability of the UBM-ECM product to manage large complex wounds makes the management of these wounds possible in less sophisticated medical settings and could prove to be a great benefit in many medically under-resourced regions of the world. The results of this case series suggest further evaluation be conducted to compare the time and quality of healing for traumatic open wounds involving exposed tendons managed with UBM-ECM versus other treatment modalities.

While flap closure of major distal lower extremity and foot wounds is the currently accepted standard of care, the present case series showed that wound treatment with UBM-ECM may provide a reasonable alternative to these more complex surgical procedures. Ease of application and minimal operative time allows for easier management of patients with multilevel leg trauma wounds, patients who are committed smokers, or patients with other comorbidities such as cardiopulmonary compromise. While wounds managed with UBM-ECM may require a longer time for wound closure as compared to flaps, and may require several applications, the avoidance of significant donor site morbidity and complex, lengthy operative procedures is often favored by patients when provided a choice. These wound management techniques can be easily performed at outlying facilities, and patients do not need to be referred to a larger treatment center for advanced care. The authors’ experience has shown that UBM-ECM wound care needs are much simpler, there are few complications, and the patient heals with a limb with a normal appearance that permits use of regular footwear. No post-healing wound revisions were required in this series, in contrast to the contour revisions often necessary in flap-based reconstruction of these difficult areas. The UBM-ECM can be utilized in wounds that are culture positive (but not grossly infected), and their use allows for more optimal timing of care for patients with these limb-critical wounds. The authors believe UBM-ECM products have utility whether they are used as the primary reconstructive modality or as an adjunct to standard reconstructive techniques. 

Affiliations: Division of Plastic and Reconstructive Surgery, Saint Louis University School of Medicine; and Department of Orthopaedic Surgery, Saint Louis University School of Medicine, St. Louis, MO

Correspondence:
Bruce A. Kraemer, MD, FACS
Pandrangi Professor of Plastic Surgery
Chief, Division of Plastic and Reconstructive Surgery
Saint Louis University School of Medicine
3635 Vista Ave
3rd Floor Desloge Towers
St. Louis, MO 63110
kraemerb@slu.edu

Disclosure: Dr. Kraemer participates in the Key Opinion Leaders Bureau for ACell Inc, Columbia, MD and has received monies for presenting his clinical experience using the porcine urinary bladder matrix-extracellular matrix products described in this paper. Dr. Geiger received travel and hotel expenses from ACell Inc to present a poster including these clinical cases at the Orthopaedic Trauma Association 2014 Annual Meeting in Tampa, FL.