Application of Viable Cryopreserved Human Placental Membrane Grafts in the Treatment of Wounds of Diverse Etiologies: A Case Series

There is evidence in the literature that viable cryopreserved human placental membrane (vCHPM) grafts are effective in treating diabetic foot ulcers and venous leg ulcers.Objective. This case series presents 3 cases of chronic ulcerations — 1 arterial ulcer (AU), 1 pressure ulcer (PU), and 1 recurrence of a pyoderma gangrenosum ulcer (PGU) — that had failed previous courses of standard wound care and were subsequently treated with vCHPM to determine if the treatment is an effective modality for treating wounds of these etiologies. Materials and Methods. This retrospective review describes 3 cases in which patients with chronic wounds that had failed standard of care treatments for more than 4 weeks were subsequently treated with weekly applications of vCHPM. Each wound area was recorded and photographed on a weekly basis and wound area reduction also was charted weekly. Results. The PU and AU both reached full closure in 4 and 5 weeks, respectively, without complication. The patient with the PGU achieved 64% closure after 9 applications of vCHPM. Conclusions. Viable CHPM is an effective treatment modality for wounds of diverse etiologies and shows better results than have been previously published with standard of care. In patients with PGUs, medical optimization and close management of comorbidities is essential in achieving optimal results.

Each patient in this cohort was treated at the Foot and Ankle Institute of Temple University School of Podiatric Medicine (Philadelphia, PA). All 3 patients demonstrated signs of chronic wounds that had failed standard of care treatments and were then treated with weekly applications of vCHPM grafts that were applied to the patients’ wounds in accordance with the manufacturer’s (Osiris Therapeutics, Inc) guidelines followed by standard of care for the specific wound. Each wound area was photographed and recorded along with wound area reduction weekly. 

Posttraumatic AU 

A 68-year-old woman with a history of noninsulin-dependent type 2 diabetes, peripheral vascular disease, chronic heart failure with lower extremity edema, myocardial infarction, peripheral ischemia, blood clots, and a thyroid tumor presented with a posttraumatic AU. The patient had a chronic left heel ulcer the year prior, and vascular studies showed an ankle-brachial index (ABI) of 0.5. A successful femoral-popliteal bypass was performed after which an ABI test showed 0.79 in the left ankle, and the patient went on to heal without complication. She subsequently presented with an AU on her left anterior lower leg secondary to an injury she sustained 4 months prior to presentation when she cut her leg on a wicker basket. 

A course of treatment was initiated that included weekly debridement to remove all nonviable tissue with daily applications of clostridial collagenase enzymatic debridement ointment (SANTYL Ointment; Smith & Nephew Inc, Andover, MA), dry sterile dressings, and a 1-week course of sulfamethoxazole-trimethoprim. The patient received weekly debridements with applications of ovine extracellular collagen matrix (OECM) and an Unna boot after the initial course of treatment proved ineffective. No other treatment was attempted. During this time, another endovascular procedure was performed in which a balloon angioplasty procedure was done and a stent was placed in the superior femoral artery of the affected limb in an effort to reestablish blood flow to the area and promote healing. 

After 6 months of wound care and vascular interventions, the wound showed several instances of progression and regression and measured 2.3 cm x 2.3 cm x 0.3 cm — 66% of the original wound area. It then was decided to begin weekly applications of vCHPM and a moist wound dressing.

The wound achieved complete closure in 4 weeks and remained closed for more than 8 weeks of follow-up (Figure 1). 

Pressure ulcer

An 89-year-old man with dementia and a history of peripheral vascular disease and venous insufficiency with peripheral edema and weak palpable pedal pulses at the level of the ankle was hospitalized after a total hip replacement and developed a 1.54-cm² PU on his right heel while bedridden. The patient was transferred to a rehabilitation facility and presented for wound care 2 weeks later. The open ulcer was painful and prevented the patient from receiving physical therapy. The ulceration was initially treated using shoe-based offloading, weekly debridement to remove all nonviable tissue from the wound bed, and daily sterile dressing applications. The patient received more than 18 weeks of a standard wound care regimen of debridement, offloading, OECM, compression, infection prevention, maintenance of a moist wound bed, and systemic disease management without indication of significant improvement.

The wound, which measured 3.96 cm², was prepared for vCHPM by debridement of necrotic debris and slough and application of an appropriately sized vCHPM directly to the wound bed along with a moist wound dressing. A foam heel cup was added to the dressing for offloading. At the next weekly visit, the wound showed improvement with new granulation tissue and a reduction in wound bed size. The ulcer measured 0.76 cm² with a 0.32 cm² skin island located lengthwise in the center of the wound. A vCHPM was reapplied and the wound was redressed. After third vCHPM application, the wound measure 0.27 cm²; no further applications were necessary, but moist dressings and padding continued. At the fourth weekly visit, the ulcer measured 0.006 cm². 

The ulcer presented completely closed in 4 weeks with 2 applications of vCHPM, and the heel continued to show signs of remodeling after 12 weeks of follow-up (Figure 2). 

Pyoderma gangrenosum 

A 68-year-old man with a history of lymphedema, diabetes, venous insufficiency, obesity, and hypertension presented with a history of chronic left lower leg ulcers that converted to pyoderma gangrenosum and, after prolonged treatment, closed and remained healed for 3 years. Despite the use of compression hose and external segmental compression at home, an ulcer recurred at the site. Because of the location and inflammatory character of the wounds, a diagnosis of a recurrence of PGU was made when the patient presented with a large geographic lower leg ulcer that measured 115 cm² in total area. He also reported that he was not monitoring his blood glucose and was unaware of his HbA_1c levels. The wounds were gently cleansed and mechanically debrided with gauze to remove slough and biofilm and an OECM was used to reduce surface matrix metalloproteinases, and an absorbent multilayer compression dressing was applied. Dressings were changed 3 times per week. Given the patient’s history of pyoderma gangrenosum and the inflammatory appearance of this wound after several attempts at standard wound care, the decision was made to pursue weekly applications of vCHPM. Vascular studies and blood work were obtained, showing an ABI of 0.8 for the affected limb and an HbA_1c of 5.2, suggesting there would be adequate vascular and systemic conditions for healing. 

After 9 weekly applications, the wound achieved 64% closure. Treatment is ongoing (Figure 3). 

There is limited evidence of documented cases of vCHPM being used to successfully treat AUs, PUs, or PGUs. All ulcers in this case series displayed results (Table) that well exceeded the established parameters of weekly healing rates for other effective wound treatment modalities.¹ 

The PU and AU both reached full closure within 5 applications and remained closed through 2 months of follow-up. The PGU displayed the poorest response to treatment; however, the patient was not compliant in the prescribed treatment regimen of using a lymphedema pump twice daily as an adjuvant therapy to the vCHPM graft applications. The treatment failed to produce wound closure after 9 applications but managed to achieve a 64% reduction in wound size. It is noteworthy that the lesion had shown only marginal improvement after several months of standard wound treatments. Inflammatory histopathology is a hallmark of PGUs and it is reasonable to infer that the positive outcome in this case may be related to the anti-inflammatory properties of vCHPM.All ulcers showed the largest appreciable amount of healing in both total area reduction and week-to-week closure percentage after the first application (Figure 4). The PU responded best to treatment; however, all wounds had healing rates that exceeded healing rates described using standard of care. The PGU case in particular represents a complex case in an individual with several comorbidities that were contributory to the outcome. Future studies should focus on each ulcer type to expand the indications for this effective modality. 

This case series illustrates that cryopreserved human placental membranes with viable MSCs can aid in decreasing the time to closure of various types of lower extremity ulcerations. The therapy is a clinically viable option for physicians to consider when formulating a treatment plan for a patient with complicated chronic lower extremity ulcers. In patients with PGUs, medical optimization and close management of comorbidities is essential in achieving optimal results. This case series indicates the need for future studies that evaluate the efficacy of this treatment. 

Affiliations: Resident Physician, Phoenixville Hospital, Phoenixville, PA; Director, Leonard S. Abrams Center for Advanced Wound Healing, Temple University School of Podiatric Medicine, Philadelphia, PA; and Temple University School of Podiatric Medicine, Philadelphia, PA

Correspondence: Derek S. Anselmo, DPM, Phoenixville Hospital, 140 Nutt Road, Phoenixville, PA 19460; derekscott.anselmo@towerhealth.org 

Disclosure: The authors disclose no financial or other conflicts of interest. The opinions or assertions contained herein are the private views of the authors and are not to be construed as official or reflecting the views of Temple University or Tower Health.