Expandable Dehydrated Human Umbilical Cord Allograft for the Management of Nonhealing Lower Extremity Wounds in Patients With Diabetes

A Case Series

Matthew Garoufalis, DPM; William Tettelbach, MD

Disclosures

Wounds. 2022;34(9):E91-E95. 

In This Article

Abstract and Introduction

Abstract

Advanced wound treatments are derived primarily from human placental membranes or animal tissue sources and composed of cellular and acellular dermal substitutes. The use of advanced wound treatments is practitioner directed and individualized to the wound characteristics. A multidisciplinary approach to wound closure is necessary, including the use of advanced treatments (eg, human umbilical cord derivatives) to achieve durable resolution of hard-to-heal wounds. In this case series, DHUC was used as an alternative to amniotic and amnion/chorion allografts for closure of a deep heel ulcer and a wound of the plantar aspect of the foot. The allografts were applied after wound closure had stalled with previous treatment attempts, which demonstrates use of DHUC in a staged approach to wound bed preparation and closure. The thickness and durability of DHUC allowed it to be used more like a skin graft for deep wounds. The meshed product can be expanded to provide a cost-effective solution to cover larger wound surfaces. It can be applied in an outpatient setting, thus avoiding more invasive and costly procedures (eg, split-thickness skin grafts). The use of umbilical allografts in the current report resulted in closure of stalled wounds and avoided hospitalization, thus reducing overall costs.

Introduction

The first reported use of amniotic membrane in medical procedures dates to 16th century China,[1] and its initial use as a wound dressing or skin substitute appears in the Western medical literature in the early 1900s.[2] Attempts to use the rich extracellular materials of the placental plate have been explored; however, to reduce the risk of an adverse immunologic reaction the tissues must first be decellularized, as with other allografts and xenografts. The DHACM allograft is an immune-privileged, minimally manipulated, dehydrated, nonviable cellular human amniotic membrane allograft that contains over 250 identified preserved regulatory factors.[3,4]

In contrast, only in the past decade have researchers begun to investigate the use of the structural and biochemically active components present within the umbilical cord.[5–8] The umbilical cord is a tissue that some have identified as a separate organ in its own right.[9] Relatively acellular and rich in regulatory compounds and extracellular matrix, this material is a thicker, structured allograft for wound closure. The DHUC allograft is a minimally manipulated, dehydrated, nonviable cellular umbilical cord allograft.[5] Its advantages over amniotic membranes include a thicker, sturdier scaffolding and an ability via meshing to be expanded over a wound while providing a protective environment that supports the healing cascade.[6]

The clinical safety and efficacy of DHUC as a treatment for nonhealing DFUs was previously established in a multicenter prospective randomized controlled trial.[6] In that study, when patients received adequate debridement, 96% of DHUC-treated DFUs closed completely within 12 weeks, compared with 65% of alginate-treated ulcers (P <.0001).[6] Preclinical testing in a rat subcutaneous implantation model demonstrated an increase in stem cell proliferation (adipose-derived and mesenchymal), fibroblast migration, and endothelial progenitor cell vessel formation in a dose-dependent manner after DHUC stimulation.[5] In addition, umbilical allografts were resorbed without fibrous encapsulation.[5]

In utero native placental tissues contain an array of growth factors that play essential roles in regulating tissue development and growth. Epidermal growth factor, transforming growth factor alpha and beta, vascular endothelial growth factor, and tissue inhibitors of metalloproteinases are a few of the regulatory proteins that play a critical role in the physiologic processes required for healthy tissue repair and that are found in DHUC.[3,5,10,11] The DHUC contains factors that are known components of a scaffold, such as collagen I, hyaluronic acid, laminin, and fibronectin, in addition to 461 proteins (growth factors, cytokines, inflammatory modulators, chemokines, proteases and inhibitors, adhesion molecules, signaling receptors, and other soluble regulators).[5]

Herein, the authors report scenarios (stalled previous treatment, poorly perfused tissue, alternative to invasive treatment) in which DHUC was beneficial in achieving wound closure; invasive skin graft techniques were avoided because DHUC can be stitched, though stitching was not necessary for the cases presented.[6] The 2 cases detailed involve a chronic heel ulcer and closure of a wound following excision of a hidradenoma from the plantar aspect of the foot. In both cases, favorable outcomes were achieved using umbilical allografts in combination with other treatment modalities.

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