Synthetic Hybrid-Scale Fiber Matrix in the Trauma and Acute Care Surgical Practice

Complex cutaneous wounds incurred from disease and trauma can be difficult to heal and may require advanced treatment options. In cases of calciphylaxis, a rare, life-threatening syndrome of vascular calcification in which occlusion of microvessels in the subcutaneous adipose tissue and dermis results in ischemic skin lesions, sepsis originating from skin lesions is the most common cause of death, resulting in a high mortality rate of 30% to 80%.¹ The biophysiology of the calciphylaxis lesion has been well described by Nigwekar et al² and Magro et al.³ Given the high morbidity and mortality associated with complex calciphylaxis skin lesions, rapid and effective healing of these wounds is critical.² Treatment options to effectively address calciphylaxis lesions are varied and involve local as well as systemic therapies.^4-6 

Similarly, the management of complex abdominal trauma with the open abdomen technique has been associated with an increased incidence of complications, including wound dehiscence, enteric fistula formation, and skin lesions, which result in increased morbidity.^7-13 The care of these patients is associated with increased costs owing to multiple factors, including prolonged length of hospital stay.^7-13

Necrotizing fasciitis is a life-threatening, rapidly spreading infection of the soft tissue characterized by necrosis and sepsis and is accompanied by severe systemic toxicity.^14,15 Given the severity of the condition, rapid diagnosis and immediate management are required.^14,15

Split-thickness skin grafts (STSGs) may be used to manage complex cutaneous wounds; however, there are circumstances in which they are limited in availability or obtaining an STSG may be imprudent (eg, calciphylaxis, debilitated patient). Drawbacks of STSGs include the need for an additional surgical procedure, use of anesthesia, use of an operating room (OR), creation of a second wound, and donor site pain and morbidity, including donor site skin infection, keloid scarring, and necrosis.^16-18 Other biologic allogeneic and xenogeneic skin substitutes also have limitations, including poor durability and longevity; they also carry the risk of disease transmission and undesirable inflammatory response.^18,19 

A fully synthetic, biocompatible, resorbable electrospun matrix composed of hybrid-scale fibers, engineered with an architecture similar to native extracellular matrix, may provide a new option for treating the lesions.^19,20 Of note, this matrix is without the risks of disease transmission or inflammatory response associated with biologic materials.^19,20 

The objective of this preliminary study was to evaluate the use of the synthetic hybrid-scale fiber matrix as a scaffold for managing 3 types of complex skin lesions: calciphylaxis, abdominal fistula, and necrotizing fasciitis of the hand and forearm.

In this preliminary case series, patients with difficult-to-heal skin lesions were treated with a synthetic hybrid-scale fiber matrix (Restrata; Acera Surgical, Inc). In all cases, multiple applications of the synthetic matrix were used based on clinician discretion. Until sufficient healing was

observed, the matrix was used in conjunction with negative pressure wound therapy (NPWT) (ABTHERA ADVANCE Open Abdomen Dressing, V.A.C. Therapy Unit, V.A.C. VERAFLO Therapy, and V.A.C. ULTA Therapy System [3M]) for the treatment of cutaneous wounds and was set to –100 mm Hg. The instillation fluid used was Vashe Wound Solution (Urgo Medical).

Each case was observed throughout the healing process, and representative photographs of the wounds were taken over the course of healing. Data were collected retrospectively by reviewing medical records. The study was exempt from institutional review board approval because of the absence of patient identifying information, the limited number of  patients (n = 3), and the insignificant risk of a retrospective study.

A total of 3 patients with complex cutaneous wounds—skin lesions owing to calciphylaxis, abdominal fistula, and necrotizing fasciitis of the hand and forearm—were included in this preliminary case series. In all cases, treatment following the use of the synthetic matrix resulted in significant healing. 

Case 1

A 42-year-old female presented to the renal dialysis unit with calciphylaxis of the bilateral breasts, hips, thighs, and abdomen. The patient had multiple comorbidities, including end-stage renal disease, hypertension, prior mitral valve replacement, and a current smoking history. The calciphylaxis skin lesions were initially managed with sodium thiosulfate daily for 8 weeks and then with heparin for 2 weeks. The lesions required surgical incision and drainage. Postoperatively, the lesion on the right thigh was managed with the synthetic hybrid-scale fiber matrix in conjunction with NPWT with instillation weekly for 5 weeks, during which time a total of 5 matrices were applied and accelerated healing was noted (Figure 1A, 1B). At that time, the transition was made to dry gauze dressing affixed with paper tape. The majority of the wound had reepithelialized by 75 days postoperatively (Figure 1C).

The bedside protocol developed by the lead author for this case (LF) is shown in Figure 2. The synthetic matrix was meshed at a ratio of 3 to 1 using a surgical mesher (Zimmer Skin Graft Mesher; Zimmer Biomet) and trimmed to size prior to application. The protocol consisted of 5 bedside applications of the synthetic matrix with NPWT, with each application having a duration of 7 days. For all applications, the wound was irrigated with instillation fluid prior to NPWT and placement of the synthetic matrix. For the second application, a silver collagen dressing (Promogran Prisma Matrix; 3M) was applied as a synergistic adjunct for locoregional control of bacterial growth in the wound. 

To determine a valid cost comparison of therapy, an institutional surgical standard practice (ISSP) treatment plan using a comparison of the cost of use of amniotic tissue or placental tissue allograft matrix was used. The synthetic matrix was applied to the patient's wound once per week for 5 weeks on the same wound; no applications of the synthetic matrix on this patient were done in the OR but instead in the inpatient unit setting. The ISSP treatment plan would have used 1 application of the amniotic tissue over the placental tissue allograft matrix once per week for 5 weeks. These once-weekly applications are not unique to the ISSP, as the instructions for many similar products indicate weekly application. The amniotic tissue sizes selected in the ISSP assessment were based on the wound size and healing pattern of the wound from the actual synthetic matrix applications. 

When considering the present institution’s implant costs only (amniotic and placental allografts and synthetic matrix), and keeping all floor materials, equipment, and labor costs equal, this analysis determined that the ISSP treatment method would have yielded an increase in cost of care of 86% compared with application of the synthetic matrix. The difference in cost expenditure between the ISSP and synthetic matrix therapy was most pronounced in week 1 through week 4 when using larger sizes of material to cover the larger wound surface area, with a very similar cost variance noted during week 5 of therapy (Figure 3). Based on this economic analysis, the ISSP is 86% more costly over 5 weeks than the synthetic matrix applications. 

Case 2

A 30-year-old male with type 1 diabetes mellitus presented with multiple blunt traumatic injuries (grade IV to V Couinaud segment 1 liver injury, grade III pancreatic head injury, grade III splenic laceration, grade II right renal laceration, and zone I retroperitoneal peripancreatic and periduodenal hematoma, as well as open facial fractures, a right open patella fracture [Gustilo-Anderson type II], and left open great toe fracture [Gustilo-Anderson type III]) following a motor vehicle accident and was taken emergently to the OR.^21-26 The patient required multiple abdominal surgical procedures to repair and control the complex liver injury (Figure 4). Despite extensive perihepatic and endoluminal drainage, the patient developed a midline abdominal incision dehiscence as a result of biliary digestion of the underlying abdominal wall fascia. The patient also manifested a delayed, midjejunal enteroatmospheric fistula with an output of 1000 mL per day. The fistula was controlled as illustrated in Figure 5.

Split-thickness skin grafting was done in an attempt to epithelialize the enteroatmospheric fistula granulation tissue, in order to safely place an ileostomy appliance. Negative pressure wound therapy was applied over the graft, per institutional protocol, with NPWT dressing (V.A.C. GRANUFOAM Dressing; 3M) over nonadherent silicone dressing (ADAPTIC TOUCH Non-Adhering Silicone Dressing; 3M), silver collagen dressing, and a meshed 3 to 1 STSG (Figure 6). The STSG and NPWT did not take to the granulation tissue around the fistula within 5 days, however, because the small intestinal succus that leaked around the ostomy appliance dissolved the STSG. 

The synthetic hybrid-scale fiber matrix was then applied to the wound in conjunction with NPWT. To begin, the synthetic matrix was meshed at a ratio of 3 to 1. The meshed synthetic matrix was applied to the wound (Figure 7A) and covered with the nonadherent silicone dressing (Figure 7B) and NPWT dressing (Figure 7C). A NPWT device (WOUND CROWN; 3M) (Figure 8A) and ileostomy appliance (Figure 8B) were then applied.

A total of 4 synthetic hybrid-scale fiber matrix applications over 6 weeks resulted in reepithelialization and complete healing around the fistula (Figure 9). The synthetic matrix remained adherent and incorporated even upon exposure to bile. The patient was taught how to care for and manage the fistula. After a total of 7 months of hospitalization for treatment following the motor vehicle accident, the patient was discharged from the hospital, because he was able to manage the remaining issues at home in part owing to the successful treatment with the synthetic matrix.

Economic data from the failed STSG and the initial surgical application of the synthetic hybrid-scale fiber matrix procedures were collected and compiled in Figure 10. The STSG total procedure cost to the facility was $14329. The synthetic matrix total procedure cost to the facility was lower, at $5210. Based on the savings calculated in this case, an economic projection analysis of 39 STSG procedures (representing the institutional average for the prior 6 months) showed that using the synthetic matrix rather than the current ISSP (ie, biologic matrix implants) would yield annual total case cost savings of $355641. 

Surgical time was also considered. Review of the surgical reports and anesthesia time in the OR as well as the OR records from this case showed the case time to be much lower with the synthetic matrix than with STSG, specifically, 54 minutes less in the OR and 29.5 minutes less cut-to-close surgical time (Figure 11).These time reductions are indirect savings of surgical resources, floor resources, and OR availability.

Case 3

A 54-year-old male presented to the emergency department for evaluation of progressive left upper extremity pain, swelling, and stiffness. The patient stated that he jammed his left hand against a car door, and over the next several days progressive pain, edema, and increased warmth developed in the left upper extremity (Figure 12). The patient did not sustain an open wound to his hand during the injury. He was initially admitted for cellulitis and started on intravenous antibiotics.

On hospital day (HD) 2, the patient’s clinical signs and symptoms continued to worsen despite the use of broad-spectrum intravenous antibiotics. At the index procedure (postoperative day [OP] 1), the patient underwent incision and drainage of the dorsal hand, volar forearm, and medial-lateral forearm. A large amount of “dishwater” purulent fluid and necrotic material was removed from the dorsum of the hand. Edema without purulence was noted in the volar-lateral forearm. The patient required 6 surgical debridements of the hand and forearm for effective clearing of the infection.

On HD 17/OP 7 (Figure 13), the infection was resolving, and the patient underwent repeat incision and drainage, washout, and application of the synthetic hybrid-scale fiber matrix and NPWT to the volar forearm wound defect (10.5 cm × 4.5 cm) and dorsal hand wound defect (6.5 cm × 5.5 cm).

On HD 22 (5 days after treatment with the synthetic hybrid-scale fiber matrix), NPWT was removed from the dorsal hand and volar surface of the forearm, and the wounds were inspected at the bedside. The synthetic matrix was well incorporated into the wounds (Figure 14). The patient was transitioned to standard of care at the bedside (ie, gauze/compressive dressing changes 3 times/week). The patient was discharged to home on HD 29 and continued receiving standard of care in the outpatient wound care clinic. Progressive wound healing was observed, and at 7.5 weeks after treatment with the synthetic hybrid-scale fiber matrix, significant epithelial coverage of the wound was achieved (Figure 15, Figure 16, Figure 17).

For this case, the ISSP was incision and drainage with subsequent STSG, a common approach and one used in multiple cases at the present authors' institution. The average total case cost, OR time, and cut-to-close surgical time at this institution was collected for STSG and for the synthetic matrix. On average, the overall cost of treatment was $876.45 more for STSG than for synthetic matrix (Figure 18). A projection of 14 incision and drainage and STSG procedures (representing the institutional average for the previous year), using synthetic hybrid-scale fiber matrix in place of current biologic matrix implants, would yield annual total case cost savings of $12270.30. Compared with the synthetic matrix, for STSG procedures the total OR time was an average of 6 minutes longer and cut-to-close surgical time was an average of 4 minutes longer (Figure 19). These time savings represent indirect savings of surgical resources, floor resources, and OR availability. 

Complex cutaneous wounds resulting from disease and injury can be difficult to heal. These wounds can result in long hospital stays, considerable health care costs, and high morbidity and mortality. The ability to rapidly reepithelialize and promote healing are essential for improving both clinical and economic outcomes. This preliminary case series provides insight into the use of synthetic hybrid-scale fiber matrix for the treatment of unique wound types studied less extensively than wounds such as diabetic foot ulcers and venous leg ulcers. The efficacy in wound closure observed with the use of the synthetic matrix to manage foot and leg ulcers^27-29 was also noted in the successful management of soft tissue lesions associated with calciphylaxis, enteroatmospheric abdominal fistula, and necrotizing fasciitis of the hand with exposed tendon.

The synthetic hybrid-scale fiber matrix offers important clinical advantages, including durability and support of wound healing, as a result of its engineered architecture, which allows for cellular infiltration, neovascularization, new tissue formation, and controlled degradation.²⁰ In contrast, current treatment options are associated with significant drawbacks. In the second case reported herein, for example, bile from a fistula destroyed the STSG used for wound management, resulting in thin granulation tissue and ineffective epithelialization. The synthetic hybrid-scale fiber matrix applied to the wound remained incorporated even while exposed to bile, however, providing a scaffold for reepithelialization and enabling complete healing of the open wound. The synthetic matrix was robust; to further enhance wound healing, the matrix. was used in conjunction with NPWT with instillation dressings. Of note, the wound healing allowed the patient to more effectively manage the fistula with an ostomy device and enabled the discharge from the high-cost hospital setting and return to home after many months. 

In addition to the clinical benefits provided by the synthetic matrix, preliminary cost analysis also demonstrated the economic benefits of the product. Compared with alternative treatment options, such as STSG and amniotic and placental allograft tissues, use of the synthetic hybrid-scale fiber matrix resulted in less OR and surgical time and lower total cost of care. In case 2, the first synthetic hybrid-scale fiber matrix application was performed 5 weeks after the failed STSG. Had the synthetic matrix been used from the outset, the patient might potentially have been discharged sooner, thereby further substantially decreasing the total cost of care. Furthermore, published literature has noted the potential institutional cost saving that may be obtained by a more efficient use of the OR.^30,31 Shippert³¹ analyzed 100 separate hospitals in the United States and noted that the OR cost ranged from $22 to $133 per minute, depending on the complexity of the intervention, with an average OR cost of $62 per minute nationally. Based on the economic analysis of time saved in case 2 (54 minutes) and using the reported range of per-minute OR cost of $22 to $133 as well as the national average per-minute OR cost of $62, it is estimated that use of the synthetic matrix would potentially result in significant cost savings (average, $3348 [range, $1188 to $7182]). For case 3, using the data obtained from this case (6 minutes saved in total OR time) as well as the low and average national OR per minute cost ($22 and $62, respectively),^30,31 the estimated potential savings with use of the synthetic matrix would be between $132 and $372. Based on the average 14 annualized rates of procedures, a potential institutional procedural cost savings of $1848 to $5208 might be achieved. 

Additionally, indirect costs exist associated with handling and preparing biologics, such as special storage needs, requirements concerning tissue banking and tracking, and complex preparation steps, whereas the synthetic hybrid-scale fiber matrix requires no specialized storage and no tissue tracking requirements, and minimal preparation is needed prior to use. The overall differences in product handling, preparation, and the benefits of the synthetic matrix compared with the biologics represent indirect savings related to the use of the synthetic matrix.

Previous work has demonstrated that the hybrid-scale fiber matrix can be used alone to successfully manage and completely close commonly studied wounds, such as diabetic foot ulcers, venous leg ulcers, pressure ulcers, traumatic and postoperative wounds, nonvenous vascular wounds, and necrotic wounds.²⁸ In this preliminary study, the synthetic hybrid-scale fiber matrix was used in conjunction with other modalities, including NPWT and a silver collagen dressing, in the management of complex wounds. The approach in this study demonstrates the versatility of the product and the possibility of use of the hybrid-scale fiber matrix with other therapies when desired, possibly resulting in synergistic effects to encourage improved healing, particularly for difficult-to-treat wounds.  

Here are limitations associated with this preliminary case series. This was a small case series with 3 patients. This is a retrospective series and is therefore dependent on the availability and accuracy of the data records. A case series is subject to selection bias because of the self-selected nature of the cases. Because of the small number of patients, it was not possible to establish a control arm for comparison; instead, historical data from the institution were used where appropriate. Owing to the retrospective nature of this study, protocols and outcomes measures were not normalized. The hybrid-scale fiber matrix was used together with other modalities, such as a silver collagen dressing, and additional work is needed to further elucidate the precise effect of each of the modalities on the healing response when used in combination. The positive outcomes observed in this study warrant further evaluation in a large randomized controlled study to investigate whether the findings reported herein are generalizable to a larger patient population and to further evaluate the effects of the hybrid-scale fiber matrix on wound healing, when used either alone or in combination with other treatment modalities.

The successful clinical application of a synthetic hybrid-scale fiber matrix, as illustrated in these cases, suggests that its use may be warranted as part of the wound care continuum for the treatment of complex skin lesions (ie, refractory to existing therapies and interventions). Use of the synthetic matrix enables healing and provides economic benefits. This product may be a reasonable alternative to STSG, even in challenging cases involving a hostile local wound environment (eg, direct bile exposure) or in which the benefits of STSG may be outweighed by possible cutaneous complications (calciphylaxis). 

Authors: Luis Fernandez, MD, KHS, KCOEG, FACS, FASAS, FCCP, FCCM, FICS¹; Adam Shar, MD¹; Marc Matthews, MD, MS, FACS²; Paul J. Kim, DPM³; Christopher Thompson, MBA⁴; Natalie Williams, MPAS, PA-C¹; and Mandy Stutsman, RN¹

Affiliations: ¹University of Texas Health Science Center, Tyler, TX; ²University of Arizona College of Medicine, Tucson, AZ; ³UT Southwestern, Dallas, TX; ⁴UT Health East Texas, Tyler, TX

Correspondence: Luis Fernandez, MD, KHS, KCOEG, FACS, FASAS, FCCP, FCCM, FICS, Department of Surgery, University of Texas Health Science Center, Tyler, TX, thebigkahuna115@gmail.com 

Disclosure: Dr Luis Fernandez is a consultant for Acera Surgical, 3M, and Urgo Medical North America/SteadMed. The remaining authors disclose no financial or other conflicts of interest.