Successful Upper Extremity Limb Salvage Using Cellular- and Tissue-based Products in a Patient With Uncontrolled Diabetes

Shawhin R. K. Shahriari, MD; Amanda C. Ederle, MD; Cees Whisonant, MD; Joshua Harrison, MD; Gregory Borah, MD; Anil Shetty, MD


Wounds. 2022;34(10):E104-E107. 

In This Article

Abstract and Introduction


Introduction: Uncontrolled diabetes causes dysfunction in all stages of wound healing, including greatly delayed wound closure owing to impaired angiogenesis. CTPs play an important role in advanced wound care, especially in complex diabetic wounds. The 3 categories of CTP are ECMs, amniotic tissues, and composite products that combine living cells and a collagen matrix. These products are available as xenografts or allografts, or as bioengineered products. ECMs provide a biological scaffold to facilitate wound healing, and these tend to modulate the wound environment and become incorporated into the wound bed.

Case Report: A right-hand dominant female with uncontrolled type 2 diabetes presented with a complex nonhealing wound of the right upper extremity; the patient was treated with CTPs after surgical intervention (incision and drainage of the abscess, open carpal tunnel release, forearm fasciotomy, and excisional debridement) for a deep forearm abscess. Exposed critical structures included flexor tendons and the median nerve. The patient received a single application of a meshed dermal regeneration template, an application of minimally processed human umbilical cord membrane, and an application of acellular fish skin, resulting in successful wound reconstruction and improved function of the right upper extremity.

Conclusion: To the authors' knowledge, this is the first described use of acellular fish skin in the setting of upper extremity reconstruction.


Type 2 diabetes is an endocrine disease in which altered metabolism of glucose leads to chronic hyperglycemia due to insulin resistance. Approximately 1 in 10 people in the United States are affected by type 2 diabetes.[1] Patients with type 2 diabetes have increased rates of soft tissue infections, which are compounded by impaired wound healing, microvascular changes, and chronic inflammation. The management of diabetic infections, wounds, and ulcers requires a multidisciplinary approach involving good nutrition, glycemic control, debridement, and antimicrobial therapy.

The impaired angiogenesis of patients with type 2 diabetes strongly contributes to the chronic, nonhealing nature of many diabetic wounds.[2] Wound healing normally progresses in a linear fashion beginning with hemostasis, followed by inflammation and proliferation, and ending with remodeling. In patients with type 2 diabetes, however, healing does not properly progress through these stages, and delayed healing leads to chronic wounds. Additionally, normal healing relies on angiogenesis to transport necessary growth factors, nutrients, and other substances to the site of injury; wounds in patients with diabetes exhibit lower capillary densities and overall decreased vascularity compared with wounds in patients without diabetes.[3] Thus, patients with the microvascular changes associated with type 2 diabetes are at increased risk of developing nonhealing wounds.[2] The literature suggests there is a 25% to 39% upper-extremity amputation rate owing to infection in patients with diabetes.[4,5] However, the rate of upper-limb amputation in patients with osteomyelitis is not significantly different between patients with diabetes and patients without diabetes (1.7% and 1.6%, respectively).[6]

To facilitate prompt closure of chronic, nonhealing diabetic wounds, it may be necessary to use CTPs. The 3 categories of CTPs are ECMs, human amniotic tissues, and composites that combine living cells and a collagen matrix. Currently, the 3 broad categories of ECM products that are available off-the-shelf are xenografts, allografts, and bioengineered products. The concept behind the use of ECMs is to provide a biological scaffold to facilitate wound healing. Additionally, ECMs modulate the wound environment and subsequently become incorporated into the wound bed.[7]

One group of ECMs is derived from human amnion. These products have been used in many settings, including for tendon and nerve wrapping. For those applications, data indicate there are fewer adhesions and less scar formation with use of human amnion, resulting in improved functional recovery.[8] Additionally, ECM derived from human amnion has antimicrobial properties, making it ideal for nerve wrapping.[8,9]

A second commonly used product in reconstruction is bilaminate neodermis. These products have been used in wounds with exposed critical structures and have become an essential tool in reconstructive surgery.[10–17] After incorporation of the neodermis, the wound is recategorized from a critical wound to one suitable for skin grafting.

The third product described in this report is an acellular fish skin. This material has been described for use in burns and DFUs, and data indicate that it offers more antimicrobial resistance than human amnion/chorion.[15–17] There are relatively limited reports on the use of acellular fish skin and, to the authors' knowledge, no study to date has used these products to cover exposed critical structures in a wound bed.

The current case report demonstrates the use of 3 ECMs—meshed dermal regeneration template (Integra Dermal Regeneration Template; Integra LifeSciences), minimally processed human umbilical cord membrane (Avive Soft Tissue Membrane; AxoGen, Inc), and acellular fish skin (Omega3; Kerecis)—in the reconstruction of a chronic diabetic upper extremity wound. This intervention ultimately led to limb salvage in a previously nonfunctional upper extremity.