According to the Centers for Disease Control and Prevention (CDC), greater than 60 percent of non-traumatic lower extremity amputations occur in patients with diabetes.1 It is clear one can attribute this to diabetic foot ulcers (DFUs), soft tissue infection and osteomyelitis. Wounds that are arrested in the chronic phase of healing become susceptible to soft tissue and bone infection, and subsequent amputation.2 This knowledge underscores the need for production of better wound care techniques and products in order to heal DFUs in a timely manner.
While there are a variety of wound care products available to aid in the healing of DFUs, for the purposes of this article, we will take a closer look at allografts. Allografts are bioengineered skin substitutes consisting of human, bovine or porcine, non-living, acellular tissue scaffold that allows host cellular ingrowth.3 Human-derived acellular dermal matrices (ADMs), a subdivision of allografts, are emerging as safe and unique tools for the healing of chronic DFUs unresponsive to traditional wound care modalities.
The human-derived acellular dermal matrices include Graftjacket (KCI), Alloderm (Lifecell Corp/KCI), Memoderm (Memometal Inc./Stryker) and TenSIX (Solana Surgical). The human-derived acellular dermal matrix generated from cadaveric skin contains proteoglycans, fibronectin, hyaluronan and vascular channels that promote tissue regrowth and revascularization, leading to regeneration rather than scar formation.4,5 These products have advantages over the bovine and porcine skin substitutes as they produce minimal inflammatory response and a decreased risk of rejection.4,6
What The Literature Reveals
Brigido performed a prospective, randomized, controlled study to evaluate the efficacy of sharp debridement plus Graftjacket application versus sharp debridement only in 28 patients with diabetes over a 16-week period.2 Results demonstrate complete healing by week 16 in 12 out of 14 patients in the Graftjacket group versus four out of 14 complete wound closures in the sharp debridement only group. The author concluded that the use of Graftjacket in addition to sharp debridement can lead to a statistically significant increased percentage of complete healing of lower extremity ulcerations.2
Winters and colleagues performed a multicenter, retrospective study including an array of lower extremity ulcerations in 100 patients treated with Graftjacket.7 The authors found the average time to matrix incorporation was 1.5 weeks, the average time to 100 percent granulation of the wound bed was 5.1 weeks and the average time to complete healing was 13.8 weeks. The matrix success rate (full epithelialization of the wound) was 90 percent.7
Reyzelman and co-workers conducted a prospective, randomized, controlled, multicenter study comparing 47 patients treated with one Graftjacket application versus 39 patients receiving standard care (moist wound therapy using alginates, foams and hydrogels as per the physician’s discretion).8 They noted complete healing in 69.6 percent of the Graftjacket group and 46.2 percent of the standard care group. The average time to healing was five to seven weeks in the Graftjacket group and six to eight weeks in the standard care group. These results demonstrate that DFUs treated with Graftjacket were two to three times more likely to heal than DFUs treated with standard wound care therapy alone.
The lead author has had experience with Memoderm, which is identical in its sterility assurance level (SAL) level to TenSIX.
The lead author has published two case studies that demonstrate the positive wound healing results of the graft. The first case study involved the use of Memoderm for a non-healing, fifth digit amputation site. In this case study, only one application of Memoderm was needed to facilitate rapid epithelialization of the ulcer site, allowing closure of the wound in roughly eight weeks.9
The second case study involved a patient with a non-healing, open guillotine transmetatarsal amputation site.10 Ninety days after applying Memoderm to the site, the lead author was able to achieve full incorporation of the graft and applied a split thickness skin graft (STSG). With full incorporation of the Memoderm product, the lead author found he could apply a much smaller STSG, leading to decreased donor site morbidity.
What You Should Know About TenSIX
TenSIX is an acellular dermal matrix product derived from human cadaveric tissue with a distinct processing technique, which sets it apart from its competitors. This product undergoes Gamma Precision Dose Sterilization to a sterility assurance level (SAL) of 106.11 The processing technique removes the epidermis and the cellular components of the tissue. This decreases the risk of an immunogenic rejection response.11
Sterility can be defined as the absence of microorganisms, including viruses, while the sterility assurance level refers to the level of sterility obtained by processing. Currently accepted pharmaceutical sterilization levels are 106, meaning there is less than a one in one million chance that one viable microorganism will be present on the sterilized item.12,13
TenSIX and Memoderm are unique in this aspect as they are among the only sterile acellular dermal matrices on the market. Many competing products undergo a similar processing technique to a sterility assurance level of 103, which does not meet the criteria for a sterile product. Furthermore, this processing technique does not disturb the biomechanical strength and biocompatibility of the tissue.11
Another important characteristic of this product is the availability of a range of thicknesses (0.4-0.8 mm) that are thinner than some of the competing products on the market.11 It is our belief that the thinner grafts allow for faster vascular migration and bridging, and subsequently increase the rate of graft incorporation. TenSIX also comes in meshed and unmeshed versions, making it an acceptable product for tendon reinforcement as well.
The lead author has had experience with this product in the form of a small case series with short-term follow up. It is the lead author’s belief that the unique qualities of the TenSIX product provide superior results with a decrease in the need for repeat graft application and re-operation/amputation rates, which also reduces costs to the patient and healthcare system.
Case Study: When A Patient With Multiple Comorbidities Has Delayed Post-Op Wound Healing
A 44-year-old female patient presented with a past medical history of type 2 diabetes mellitus, chronic renal failure on hemodialysis, peripheral vascular disease and had an angioplasty procedure on the left lower extremity. The patient has delayed post-op healing on the left fourth and fifth metatarsals after ray resections for necrotizing infection, leaving an open amputation site.
With the patient under intravenous sedation with local anesthesia, we prepped and draped the wound with the double drape system, and marked the surgical limb. We used hydrojet debridement to remove the superficial layer of tissue and irrigated the graft application site with sterile saline solution. We then changed gowns, gloves and straps. All bleeders were under control.
We opened an acellular dermal allograft (4 cm x 8 cm x 0.4 mm) from sterile packing and placed it in sterile saline solution for rehydration. After rehydrating the graft, we placed it over the entire wound and sutured the graft with Prolene 5-0 suture. We subsequently employed negative pressure wound therapy (NPWT) (VAC therapy, KCI) at 125 mmHg.
The patient was subsequently discharged from the hospital and returned to the extended care facility. At day five, clinicians removed VAC therapy and placed a thin layer of oil emergent gauze and a 4 x 4 felt with mineral oil over the wound surface. Daily dressing changes with oil emergent gauze and saline-soaked, mineral oil took place over the postoperative course. The patient’s wound was healed at day 90.
Case Study: Addressing Delayed Healing Of A Fifth Ray Amputation Site
A 62-year-old male patient presented with a history of type 2 diabetes mellitus and peripheral vascular disease. He had a peripheral artery bypass graft of the right lower extremity and subsequent amputation of the right fifth ray for wet gangrene. We noted delayed healing of the right fifth ray amputation site.
We brought the patient to the operating room. After providing local anesthesia with intravenous sedation, we debrided the superficial surface of the wound with the Versajet (Smith and Nephew) hydrojet debridement tool. After irrigating the graft application site with sterile saline solution, we placed a 4 cm x 4 cm x 0.40 cm TenSIX sterile acellular dermal allograft over the wound surface. Utilizing 2-0 Prolene simple interrupted sutures, we sutured the graft around the wound periphery with 2 mm overlap. We subsequently applied VAC therapy.
At five days post-op, clinicians removed VAC therapy. We placed Adaptic (Systagenix Wound Management) oil emergent gauze over the wound surface and the patient had daily dressing changes. We noted rapid in-growth of granulation tissue into the wound surface followed by rapid epithelial coverage. The graft site was healed at 20 days after application of the TenSIX allograft. The patient subsequently wore athletic shoes and returned to work.
In conclusion, the goal of the podiatric surgeon is limb salvage and there are a variety of wound care products available to aid in this task. Allografts present a viable option for rapid healing of chronic DFUs. Human-derived acellular dermal matrices create a minimal inflammatory response with a decreased risk of rejection.4,6
The TenSIX human-derived acellular dermal matrix product provides a sterile scaffolding to allow for rapid vascular ingrowth and epithelialization while reducing the risk of rejection and infectious complications in the typical immunocompromised patient with chronic non-healing DFUs.
Dr. Rice is an Assistant Clinical Professor in the Department of Orthopaedics and Rehabilitation at the Yale University School of Medicine. He is a Fellow of the American College of Foot and Ankle Surgeons.
Dr. Pryzbylski is a second-year podiatric surgical resident at the Yale University School of Medicine.
1. Centers for Disease Control and Prevention. 2011. National diabetes fact sheet: National estimates and general information on diabetes and prediabetes in the United States, 2011. Atlanta, GA: U.S. Department of Health and Human Services, 2011.
2. Brigido SA. The use of an acellular dermal regenerative tissue matrix in the treatment of lower extremity wounds: a prospective 16-week pilot study. Int Wound J. 2006;3(3):
3. Steinberg JS, Weber B, Kim PJ. 2009. Bioengineered alternative tissues for the surgical management of diabetic foot ulceration In: T. Zgonis ed. 2009. Surgical Reconstruction of the Diabetic Foot and Ankle, Ch. 9, Lippincott Williams and Wilkins, Philadelphia, PA, 2009, pp. 100-115.
4. Life Cell Corporation. Alloderm defined. LifeCell Corporation; Branchburg, NJ, 2004.
5. Lin HJ, Spoerke N, Deveney C, Martindale R. Reconstruction of complex abdominal wall hernias using acellular human dermal matrix: a single institute experience. Am J Surg. 2009;197(5):599-603; discussion 603.
6. Gaertner WB, Bonsack ME, Delaney JP. Experimental evaluation of four biologic prostheses for ventral hernia repair. J Gastrointest Surg. 2007;11(10):1275-85.
7. Winters CL, Brigido SA, Liden BA, et al. A multicenter study involving the use of a human acellular dermal regenerative tissue matrix for the treatment of diabetic lower extremity wounds. Advances in Skin and Wound Care. 2008;21(8):375-381.
8. Reyzelman A, Crews RT, Moore JC, et al. Clinical effectiveness of an acellular dermal regenerative tissue matrix compared to standard wound management in healing diabetic foot ulcers: a prospective, randomized, multicentre study. Int Wound J. 2009;6(3):196-208.
9. Rice A. Memoderm Acellular Dermal Matrix: Used to treat a complex diabetic foot wound. Data on file, Stryker, 2011.
10. Rice A. Memoderm Acellular Dermal Matrix: Used to treat transmetatarsal amputation. Data on file, Stryker, 2011.
11. Solana Surgical. TenSIXTM acellular dermal matrix. Solana Surgical; Memphis, TN, 2012.
12. Von Woedtke T, Kramer A. The limits of sterility assurance. GMS Krankenhhyg Interdiszip. 2008;3(3):19.
13. Srun SW, Nissen BJ, Bryans TD, Bonjean M. Medical devices SALs and surgical site infections: a mathematical model. Biomed Instrum Technol. 2012;46(3):230-237.
For further reading, see “Acellular Orthobiologics: Can They Improve Wound Healing?” in the September 2008 issue of Podiatry Today. To access the archives, visit www.podiatrytoday.com.