Surgical Application of Viable Cryopreserved Placental Membrane for the Treatment of Chronic Wounds in 12 High-risk Patients

Treatment of lower extremity ulcers remains a challenge to physicians and surgeons. These wounds lead to an increased risk of amputation and increased mortality rate and must be treated aggressively, in many cases requiring surgical debridement, to prevent these complications. The objective of this retrospective case series is to evaluate the safety and efficacy of a viable cryopreserved placental membrane (vCPM) in 12 patients with 16 wounds of mixed etiologies when surgically debrided and augmented with vCPM 1 time, followed by standard of care (nonadherent dressing, gauze, and compression) until healed. The results of this case series demonstrate that the surgical application of vCPM can be used as an alternative treatment for high-risk patients with chronic lower extremity wounds. 

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Treatment of chronic wounds can be time consuming and costly, especially in patients with comorbidities such as diabetes and peripheral vascular disease.¹ In the United States, an estimated 30.3 million people are affected by diabetes mellitus, with a prevalence of 9.4%; the percentage of adults with diabetes increased with age in 2015, reaching a high of 25.2% among those aged 65 years or older.² A serious complication of diabetes is the nonhealing foot ulcer, the most common cause of lower extremity amputation (LEA) in diabetics according to the Centers for Disease Control.³ About 82% of LEAs are performed on patients with diabetes, with 50 000 amputations performed every year in the United States because of nonhealing diabetic foot ulcers (DFUs).⁴ van Houtum⁵ found that people with diabetes are 15 to 20 times more likely to have a LEA compared with healthy individuals, and the majority (up to 85%) of diabetes-related amputations are reported to be preceded by a poor healing ulcer. A 2013 study by Jones et al⁶ showed mortality risk was also high in patients with peripheral artery disease (PAD) undergoing a major LEA, with almost half of all patients with PAD dying within a year of major LEA.

Presented herein are 16 wounds of various etiologies treated with aggressive surgical wound management and augmented with a viable cryopreserved placental membrane (vCPM; Grafix; Osiris Therapeutics, Inc, Columbia, MD) in a 1-application surgical technique.

The Table summarizes the demographics of 12 patients (all male) with 16 open wounds of various etiologies (venous leg ulcers, diabetic foot wounds, necrotizing fasciitis, and vascular ulcers) who underwent aggressive surgical debridement and irrigation augmented with vCPM at the time of surgery. Past medical history included diabetes mellitus, coronary artery disease, congestive heart failure, hypertension, venous insufficiency, end-stage renal disease, chronic kidney disease, and peripheral vascular disease. All patients underwent incision and drainage (I&D) procedures with aggressive debridement and irrigation. Patients were hospitalized at the Sutter Medical Center (Sacramento, CA) and received intravenous antibiotics until discharge.

All procedures were augmented with vCPM, a human tissue allograft regulated by the US Food and Drug Administration (FDA) under 21 CFR Part 1271 Part 361 Human Cells, Tissues, and Cellular and Tissue-based Products (HCT/Ps). Preparation of the tissue is by a proprietary cryopreservation method that allows for tissue-screening time and long-term storage. The vCPM retains components found in native placental tissue (3D extracellular matrix, growth factors, living epithelial cells, fibroblasts, and mesenchymal stem cells) as well as properties of native tissues, including anti-inflammatory, anti-adhesion, antifibrotic, antimicrobial, and angiogenic.^7-9

The vCPM was thawed and applied to the debrided wounds following I&D in the operating room. It was placed into deeper wound tunnels, over exposed bone and tendon, and on the wound surface, followed by a nonadherent dressing layer (ADAPTIC TOUCH Non-Adhering Silicone Dressing; Acelity, San Antonio, TX) and standard gauze and a compression dressing.¹⁰ The use of compression was determined by the treating physician as per established standard wound care protocols. Wounds were then followed weekly and treated with standard of care (SOC; nonadherent dressing, gauze, and compression) until healed, which was an average of 9.19 weeks (2.3 months; range, 3 weeks–6 months). 

This case series was exempt from Institutional Review Board review due to the retrospective nature of the analysis. Written informed consent was obtained, and personal information was deidentified consistent with the Health Insurance Portability and Accountability Act of 1996.

All 16 wounds closed with 1 surgical application of vCPM, despite high-risk comorbidities that contributed to the nonhealing ulcers in all 12 patients. No complications or adverse events were reported. The average age of patients was 62.42 years (range, 40–90 years) and average body mass index was 28.29 (range, 19.1–41.3). The average wound size was 51.06 cm² (range, 3.3–128.0 cm²). The average time to heal was 9.62 weeks (range, 3–24 weeks). Patients were treated from 2014 to 2017, and there has been no recurrence of any of the wounds over the last 4 years of follow-up.

Case 1: gangrene
A 54-year-old man (patient 12 in the Table) with diabetes, cellulitis, PAD, and acute osteomyelitis with gangrene of the left dorsal foot and hallux was treated with I&D, debridement, amputation of the hallux, and 1 surgical application of vCPM to the exposed wound. Wound size was 10 cm². The wound healed in 12 weeks with only SOC after vCPM application (Figure 1).

Case 2: necrotizing fasciitis
A 58-year-old man (patient 11 in the Table) with a past medical history of diabetes, congenital heart failure, hypertension, and drug use presented with necrotizing fasciitis in the right foot. Incision and drainage was performed and followed by 1 application of vCPM over the 39-cm² wound with exposed bone and tendon. The wound healed in 20 weeks with SOC (Figure 2).

Case 3: foot ulcer
A 64-year-old man (patient 7 in the Table) with a past medical history of diabetes, cellulitis, psychosis, atrial flutter, chronic lymphocytic leukemia, and congestive heart disease was treated for an infected ulcer of the right foot with I&D, debridement, and 1 application of vCPM to the 98.5-cm² exposed wound previously present for 4 months. After vCPM application, the wound granulated in 1 week and healed in 12 weeks with only SOC (Figure 3).

Case 4: diabetic foot infection
A 61-year-old man (patient 3 in the Table) with diabetes, acute renal failure, anemia, PAD, and hypertension was admitted with a plantar diabetic foot infection. Incision and drainage and revascularization was performed, followed by vCPM application and intermittent negative pressure for 5 days, as needed. The 25-cm² wound was granulated in 1 week and healed in 23 weeks (Figure 4).

Whether related to diabetes mellitus or vascular compromise, complications of chronic open wounds include sepsis, osteomyelitis, gangrene, amputation, and death.¹¹ Surgical management is often necessary and/or preferred to improve outcomes and reduce complications. In order to decrease the high amputation rates in people with diabetes, methods must be devised to improve DFU care to heal them before progression. According to a study by Tan et al,¹² early aggressive treatment of foot infections with surgical treatment and antibiotics reduced the need for amputation as well as the length of hospital stay.

There are many options for adjunct therapy when surgically debriding wounds, and with recent advances in skin substitutes and their preservation methods, these products are readily available to the surgeon. Placental tissue has been used to treat wounds for more than 100 years due to its anti-inflammatory, antioxidant, antimicrobial, and angiogenic properties.^7-9 Recent advancements in tissue processing make this viable allograft commercially available. Clinical studies^13-15 reported durable closure of chronic wounds of various etiologies with vCPM.Suzuki et al¹⁴ showed clinical effectiveness in complex wounds characterized by exposed bone, tendon, muscle, or hardware using vCPM; all 12 cases resulted in granulation over the exposed structures followed by complete wound closure. Frykberg et al¹⁵ also reported the positive clinical outcomes of vCPM in the management of complex DFUs with exposed tendon and/or bone, showing that 96.3% of patients achieved 100% granulation and 59.3% achieved complete wound closure by 16 weeks.

Limitations of this series include the small population size. Larger prospective studies are needed to better evaluate the clinical outcomes. One-time use of vCPM is not common; serial weekly applications are recommended due to the daily decline in cell viability and tissue resorption. Patient socioeconomic conditions, compliance, overall patient health, product availability, and cost also contribute to a surgeon’s choice of procedure and product for their patients. However, this series detailing high-risk, compromised patients shows that with aggressive and meticulous debridement of devitalized tissue, close follow-up, regular dressing changes, and the use of compression, certain high-risk patients with complex wounds can benefit from a single use of surgically applied vCPM.

Clinical outcomes in this retrospective series show safety and efficacy of vCPM as a 1-time surgical application, with durable closure and no wound-related or product-related complications in the treatment of chronic, complex, nonhealing wounds of various etiologies in high-risk patients. Larger, prospective, randomized clinical trials will need to be conducted in order to further establish the clinical effectiveness of surgical vCPM application in the treatment of chronic wounds.

Authors: Walter F. D’Costa, DPM¹; and Dorothy H. Kurtz Phelan, DPM²

Affiliations: ¹Wound Care Director, Sutter Medical Center, Santa Rosa, CA; and ²Osiris Therapeutics, Inc, Columbia, MD

Correspondence: Walter F. D’Costa, DPM; Northern California Foot and Ankle Center of Santa Rosa, 2281 Cleveland Avenue, Santa Rosa, CA 954032; walterfdcosta@gmail.com

Disclosures: Dr. Walter F. D’Costa is a paid speaker for Osiris Therapeutics, Inc (Columbia, MD). At the time of acceptance, Dr. Dorothy H. Kurtz Phelan was a paid employee of Osiris Therapeutics, Inc. No funding was provided for this case series by Osiris Therapeutics, Inc.