Wound healing is a sophisticated, interactive process during which tissue repairs itself.1,2 The wound healing process occurs through a series of 4 stages: hemostasis, inflammation, proliferation, and remolding. Through this process, the interaction between inflammatory mediators, local cells, and the extracellular matrix (ECM) actively contributes to the aforementioned stages of healing.3 Chronic wounds are defined as wounds that fail to heal within a period of 3 months.1 These nonhealing wounds represent a significant health care issue affecting more than 1% of the western population.4 Chronic wounds also impose an enormous financial burden on the health care system, resulting in costs of more than $25 billion annually in the United States alone.1
According to the National Pressure Ulcer Advisory Panel (NPUAP), “a pressure injury/ulcer is localized damage to the skin and underlying soft tissue usually over a bony prominence or related to a medical or other device.”5,6 Pressure ulcers present first as unbroken skin and then frequently progress to an open ulcer that may be painful. The wound develops due to a combination of pressure and shear stress. Soft tissue may exhibit different tolerance to pressure and shear due to variance in tissue perfusion, microclimate, nutritional status of the patients, comorbidities, and the condition of the tissue.4
Ulcers classified as chronic wounds are thought to be stuck in the inflammatory phase of wound healing. This current concept suggests that a local increase in the level of proteases, such as matrix metallopeptidases, in the wound bed leads to a stalled wound healing process. The hypoxic microenvironment breaks down important growth factors and thus prevents the wound from continuing to the next phase of repair (proliferative phase) to form granulation tissue and a new provisional matrix for remodeling and healing.7
Collagen is the most abundant protein in the human body, and it is a fundamental component in the ECM.8 It is also an obligatory protein in all stages of the wound healing cascade. Fibroblasts secrete collagen in the proliferative phase to direct keratinocyte migration to areas of the injured epidermis. A collagen-rich dressing induces localized production and assembly of collagen.9 Furthermore, it helps create an ideal environment for wound healing through recruiting repair cells such as fibroblasts and macrophages. In addition, this type of dressing is convenient to apply and remove and provides an absorptive, moist environment to promote healing. Oasis Ultra (small intestinal submucosa extracellular matrix [SIS-ECM]; Smith & Nephew, Fort Worth, TX) is a porcine-based, triple-layered ECM wound wrap that contains different types of glycosaminoglycans such as heparan sulfate, hyaluronic acid, and chondroitin sulfate.10 In addition, it contains adhesion molecules such as fibronectin and laminin along with various growth factors such as transforming growth factor, basic fibroblast growth factor, and vascular endothelial growth factor (VEGF).3 Collagen-rich biomaterial is often synthesized from avian, bovine, and porcine collagen.
The SIS-ECM is made from porcine small intestinal submucosa. This product has been previously reported to produce a dressing that inactivates the tissue metalloproteases, thereby preventing destruction of the provisional ECM.7 Its composition stimulates cell migration, reduces inflammation, and provides moisture to the wound bed; SIS-ECM also grants structural support and enhances cellular proliferation and attachments. The SIS-ECM has been employed for a variety of wounds including chronic vascular, venous, and diabetic ulcers; partial-thickness burns; donor sites and skin graft preparation; and partial- and full-thickness, surgical, and traumatic wounds.7
Closed suction drainage systems are used to enable mass transport of fluid from the body as an adjunct to surgical procedures. For instance, a chest tube using this system can evacuate air from the pleural cavity. Moreover, closed suction is also used to drain stomach contents, which facilitates small intestinal obstruction treatment. High suction can even remove tissue from the body, similar to liposuction. In 1997, Morykwas et al11 faced a significant number of complicated wounds and tried to come up with a better approach to treatment. Their first idea was to develop a way to apply suction on the wound to pull the wound edges together. Based on this idea, they designed several prototypes that expedited wound healing.11 The prototype that has had significant success in treating wounds contains an open pore polyethylene foam positioned in the wound, shielded by a semi-adhesive dressing, and linked by tube to a suction source. They named this technique negative pressure wound therapy (NPWT). An alternative description that more precisely defines the physics of the method is microdeformational wound therapy. This device by Morykwas et al11 has changed the course of treatment for many patients with complex wounds even to this day and has become the standard of care used to heal complex wounds in the United States.12 According to Orgill and Bayer,9 NPWT’s mechanisms of action are divided into primary and secondary effects that affect the process of wound healing.
The primary effects of NPWT include tissue macrodeformation, in which the wound edges are pulled together by the open pore foam; however, that effect depends on the mobility of the tissue surrounding the wound. Furthermore, microscopic deformation at the wound surface stretches the cells and enhances cell proliferation and division.13 In addition, NPWT has the ability to eliminate large amounts of extracellular fluid and affords an isolated moist environment for the wound to heal. The secondary effect includes promoting granulation tissue via upregulation of the hypoxia-inducible factor 1-alpha-VEGF pathway through the microdeformation effect, which promotes localized hypoxia close to the wound surface.9 Negative pressure wound therapy also modulates inflammation, induces cellular proliferation, and changes the bacterial levels in the wound. It is indicated for various types of wounds, including acute, subacute, chronic, traumatic, or dehisced wounds; NPWT also is indicated for partial-thickness burns; ulcers, including diabetic, pressure, or venous insufficiency; and flaps and grafts. Negative pressure wound therapy is contraindicated in malignancy (since proliferation is induced by NPWT and may enhance malignant growth), untreated osteomyelitis, nonenteric and unexplored fistulas, necrotic tissue with eschar, and sensitivity to silver (GranuFoam Silver [KCI, an Acelity Company, San Antonio, TX] dressing only).9
The present study tested the hypothesis that combining SIS-ECM with NPWT would increase wound healing over NPWT alone in chronic pressure ulcers; the authors suggest that this combination could have added benefit in the population of patients with difficult-to-treat stage 4 pressure ulcers.