Clinical Usage of an Extracellular, Collagen-rich Matrix: A Case Series

OASIS Ultra (Smith & Nephew, St. Petersburg, FL) is an extracellular, collagen-rich matrix derived from submucosa of porcine intestine. It is composed of collagen type I, glycosaminoglycan, and proteoglycans. This extracellular matrix (ECM) differs from the single layer in thickness and offers ease of handling and application. It also stimulates cell migration and structural support, provides moisture environment, decreases inflammation, and induces cell proliferation and cellular attachments. In this case series, the authors present their experience with this product in various clinical scenarios. Materials and Methods. The authors used the product in a variety of wounds with different etiologies to test the clinical outcome of the ECM. This was an observational case series with prospective review of 6 different patients with different types of wounds who received treatment with the ECM during their treatment. The product was applied on the following types of wounds: chronic venous ulcer, nonhealing Achilles tendon vasculitic wound, Marjolin’s ulcer, posttraumatic wound, stage IV sacral-coccygeal pressure wound, and complicated transmetatarsal amputation of gangrenous left forefoot diabetic wound. Results. All of these wounds healed within the expected time periods and without complications. In general, healing was achieved in 4-16 weeks using 1-12 applications of the ECM. Conclusion. Wounds with different etiologies were successfully treated with an extracellular, collagen-rich matrix. By replacing the lost ECM to guide cellular growth and migration, this product did ultimately hasten the healing process.

Wound healing is a complex, dynamic process of replacing devitalized and missing cellular structures with new tissue. Collagen, which is a biomaterial, establishes a large part of the dermis and provides high tensile strength, low extensibility, and low antigenicity that affects the wound healing process.¹ Collagen is a fundamental protein in the connective tissue matrix, increasing the ability of keratinocytes to migrate toward the area of the damaged epidermis that needs replacement.² Collagen is released from fibroblasts, is the most abundant structural protein in the human body, and is mandatory for all phases of the wound-healing cascade. A collagen-based dressing enhances the production and organization of collagen by fibroblasts. Furthermore, a collagen dressing helps create a suitable environment to promote healing by stimulating the recruitment of specific cells such as macrophages and fibroblasts. Moreover, collagen dressings are easy to apply and remove, and are helpful to the healing process by providing a moist environment to promote healing. Collagen-based biomaterial can be made from bovine, avian, or porcine collagen. Plant-based biomaterial and oxidized regenerated cellulose, both natural biomaterials, are combined together to produce a dressing that has the capability to inactivate tissue metalloproteinase. Matrix metalloproteinase (MMP) is an enzyme responsible for the breakdown of the extracellular matrix (ECM), which has important growth factors required for wound healing.³ The extracellular, collagen-rich matrix used in this case series (OASIS Ultra, Smith & Nephew, St. Petersburg, FL) is a naturally derived inactive porcine small intestinal submucosa (SIS). This ECM differs from others in thickness and also offers ease of handling and application. It consists of collagen and other ECM proteins such as glycoproteins, glycosaminoglycan, and proteoglycans, which are important to maintain a wide range of functions imperative to build a productive wound-healing environment. The ECM product’s structure provides stimulation to cell migration, structural support, a moist environment, decreases inflammation, and induces cell proliferation and cellular attachments. It also provides a natural tissue scaffold, which is an essential component of the healing process. The ECM can be used in different kinds of wounds including chronic vascular ulcers, diabetic ulcers, donor sites, partial-thickness burns, pressure ulcers, venous ulcers, traumatic wounds, partial-thickness and full-thickness wounds, surgical wounds, and even in preparation for skin grafts. In this case series, the authors present their experience at the Kettering Health Network Wound Healing Center at Sycamore Medical Center, Miamisburg, OH with this extracellular, collagen-rich matrix and its use in 6 different cases resulting from different etiologies.

Case study 1. A 68-year-old male presented with a 2-year history of chronic venous ulcers located at the medial aspect of his right leg, resulting from chronic venous hypertension (Figure 1A). He was referred to the authors’ wound clinic by the vascular surgery department after failed standard therapy with compression therapy and absorptive dressings for 2 years.

Punch biopsies of the wound bed ruled out malignancy. He was then started on weekly ECM applications with compression therapy (PROFORE Multilayer Compression Bandage System, Smith & Nephew, St. Petersburg, FL). A total of 12 applications were approved and applied. The ECM product was applied weekly unless remnants of the product were seen adhering to the wound bed, then the application was delayed until the next week. Figures 1B-1E show the progression of the wound after 12 applications of the ECM, where 95% healing was achieved in 4 months. Figures 1B and 1C show the caramelization seen in the wound bed, which represented the remnants of the ECM product. 

Case study 2. A 77-year-old-female presented with a nonhealing wound to her left Achilles tendon that had lasted for 1 year. The wound bed was covered with thick slough (Figure 2A). The patient was receiving daily prednisone for a platelets disorder and also had vasculitis. The patient was taken to the operating room and underwent surgical debridement of her wound followed by the ECM application to promote granulation at the wound bed (Figure 2B). Surgical pathology and cultures were performed. The pathology didn’t show any malignancy and the soft tissue culture grew Staphylococcus aureus sensitive to doxycycline. Figure 2C shows the ECM covering the left Achilles tendon ulcer 2 weeks after application. One week later, the patient returned to the operating room and received a split-thickness skin graft for a permanent coverage of her wound. Figure 2D shows the skin graft covering the wound 2 weeks after the procedure. 

Case study 3. A 78-year-old male presented with a chronic venous ulcer wound on his right leg of 2 years duration. The patient had a chronic unstable scar from cast application 15 years prior. The wound bed was covered with friable granulation tissue and slough (Figure 3A). Surgical debridement was performed and the pathology revealed Marjolin’s ulcer, a squamous cell carcinoma. The patient was returned to the operating room for a surgical excision of the carcinoma with frozen section to clear the margins (Figure 3B). One week later, the ECM product was applied in the outpatient setting along with compression therapy. Figure 3C shows the wound 1 week after application. The following week, a second application was performed in the wound center. Figure 3D shows the wound 4 weeks after the second application. Six weeks after the second application, the ulcer was completely healed (Figure 3E). 

Case study 4. The patient is a 66-year-old female with a history of chronic respiratory failure, and she took coumadin for atrial fibrillation. She was admitted to Sycamore Medical Center, Miamisburg, OH, after sustaining trauma to her right hand, resulting in a large hematoma (Figure 4A). After administration of coumadin was stopped for 5 days, the patient was taken to the operating room and underwent surgical debridement of the hematoma, which left  partially exposed extensor tendons (Figure 4B). Figure 4C shows an intraoperative view of the ECM covering the wound. Figure 4D demonstrates the wound 2 weeks postapplication. Only 1 application was required to achieve complete healing in 4 weeks (Figure 4E). 

Case study 5. An 82-year-old male was admitted to Sycamore Medical Center, Miamisburg, OH, with idiopathic peripheral neuropathy and a 3-month-old stage IV sacral coccygeal pressure wound that was previously debrided and osteomyelitis was ruled out with a bone biopsy (Figure 5A). After his discharge, he followed up at the wound center and the ECM and negative pressure wound therapy (NPWT) were applied. Negative pressure wound therapy was applied over the ECM in this case as a bolster dressing to protect it. The ECM was applied weekly and NPWT was changed twice a week. A nonadherent adaptic layer was placed between the ECM and NPWT. Figure 5B shows the wound 1 week after the first application of the ECM. Off-loading using appropriate cushion and air mattress was continued at the patient’s home, along with nutrition support with the use of protein supplements. Figure 5C shows the pressure ulcer 3 weeks later and after 4 applications of the ECM. After 3 months and 11 applications of the ECM, the patient’s wound had completely healed (Figure 5D). 

Case study 6. A 63-year-old male patient with diabetes status post transmetatarsal amputation (TMA) of gangrenous left forefoot with flaps closure presented to the authors’ wound center for follow-up after amputation. The surgery was complicated with postoperative dehiscence requiring debridement. A total of 3 ECM applications were required over a 2-month period. Figures 6A and 6B show intraoperative views of wound debridement with the first ECM application, medial, and frontal views, respectively. Figures 6C and 6D show the ECM’s third application, medial, and frontal views, respectively, in an outpatient setting. Figures 6E and 6F show nearly healed TMA wounds at 2 months and after 3 applications of the ECM. 

The healing of chronic wounds such as venous ulcers stalls in the inflammatory phase. Some studies have shown the standard of care is not enough to treat such conditions.⁴ Therefore, the idea of introducing a bioactive multiple structural layer like the extracellular, collegen-rich matrix used in this study was to achieve better healing within a reasonable amount of time with minimal complications. This case series has shown the promising effect of the ECM in healing a variety of wounds. Porcine SIS is mainly composed of type I collagen fibers, and also contains other types of collagen such as type III, IV, VI, and a minor amount of elastin. Glycoproteins, such as fibronectin and laminin, which play a crucial role in managing cell adhesions to the ECM, have also been found in this extracellular, collegen-rich matrix. Glycosaminoglycan and proteoglycans have also been identified in the ECM product and act by providing cell attachment by facilitating growth factor binding sites.^4-6 Chronic wounds are deficient in ECM, which contributes to the wound healing process. Moreover, many studies have mentioned the strong correlation between high MMP levels and wound chronicity.^4,7 In an important in vitro study using human keratinocytes, Shi and colleagues⁸ revealed clear interaction between MMPs and SIS. The study investigated cell migration in the presence of MMPs and an SIS-treated solution. The data gathered from the study indicated that keratinocyte migration in vitro was inhibited by MMPs; however, this inhibition drastically decreased by preincubating the MMP solution with the ECM product.^4,8 Therefore, applying the ECM product on chronic wounds has been found to significantly increase the rate of wound healing compared to the standard of care alone.⁴ In addition, the ECM product is biodegradable and by attaching it to the wound bed it minimizes the activity of MMPs and increases the release of growth factors.⁴

In the authors’ case series, the extracellular, collagen-rich matrix was used instead of the single-layer product from the same manufacturer, which could have been insufficient especially in load-bearing sites. Therefore, the strength of the ECM product, along with its therapeutic effect, was increased by creating a 3-layer matrix.⁹ In addition, a multilayer SIS such as the product used in this case series is expected to stay longer in the wound bed compared to the single-layer SIS.⁴ Currently, this extracellular, collagen-rich matrix is being used on a variety of wounds including pressure ulcers, vascular ulcers, diabetic ulcers, partial-thickness burns, traumatic wounds, surgical wounds, and others.

In this case series, the authors present their experience with an extracellular, collagen-rich matrix in various clinical scenarios. Wounds with different etiologies were successfully treated with this product, which played an important role in replacing the lost ECM to guide cellular growth and migration and ultimately quicken the healing process. This ECM product should be considered in difficult clinical situations, including acute and chronic slow-healing wounds.

Affiliations: Pharmacology and Toxicology Department, Boonshoft School of Medicine at Wright State University, Dayton, OH; and Plastic and Reconstructive Surgery, Boonshoft School of Medicine at Wright State University, Dayton, OH; Department of Dermatology, Boonshoft School of Medicine at Wright State University, Dayton, OH  

Correspondence:
Richard Simman MD, FACS, FACCWS
Richard.simman@wright.edu

Disclosure: The authors disclose no financial or other conflicts of interest.