Limb Salvage Using Human Placental Allografts: Adding to the Reconstructive Ladder Paradigm ()
1. Introduction
Davis (1909) and Sabella with Stern (1913) were pioneers in placental tissue applications for wound healing [1] [2] [3] [4] . Technology revolutionized the development of biological wound dressings for clinical use. Human placental allografts are the latest treatment modalities for chronic wounds, diabetic ulcers, limbs, and tendons [5] . Exposed bone or tendon in burn or trauma extremity injuries may require surgical flaps or amputations for healing. Purion® processed dehydrated human amnion/chorion membrane allografts (Dhacm, AMNIOBURN®), decellularized human collagen matrix (dHCM), dehydrated umbilical cord (dHUC, EPICORD®), and micronized dehydrated human amnion/chorion membrane allografts (mdHACM) from MIMEDX Group, Inc. (Marietta, GA) have been used as an adjunct to salvage injured human extremities with tendon and bone exposure [6] - [11] . They contain non-viable cells, and over 250 identified regulatory proteins (growth factors, chemokines, cytokines, and metalloproteinases tissue inhibitors [TIMPS]) [6] [7] [8] [9] . In vivo, many of these regulatory proteins are known components in the tissue healing cascade. In vitro, these factors have been shown to stimulate tissue growth, regeneration, stem cell migration in animal models, fibroblast proliferation, and decreased inflammation [6] [7] [8] [9] . In 2017, Glat and Davenport recommended that placental allografts become adjuvant therapy in the surgical Reconstructive Ladder Paradigm for limb salvage [12] . Wound closure and limb salvage were successful with the combined application of dHCM, and dHACM, except for occasional difficulties with injured tendon and bone [11] . This case report illustrates successful limb salvage and full tendon/bone coverage with granulation tissue through the addition of dHUC allograft and mdHACM injections into the tendons. Placental allograft applications are described for limb reconstruction without the use of free tissue or rotational flaps.
2. Case Report
Our patient was a Hispanic man with a past medical history of gout and obesity (BMI 32 kg/m2). He lived at home with his family (Table 1). While bicycling outside his home, he was assaulted with a Molotov cocktail and sustained second and third degree burns to both lower extremities. The left leg had a 9.5% total burn surface area (%TBSA) and the right leg had a 5.5% TBSA (Figure 1). Muscles, tendons (tibialis anterior, flexor digitorum longus, Achilles), talar and tibial
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Table 1. Patient demographics and characteristics.
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Figure 1. Second and third degree burn injuries; after initial debridement; and twenty-two weeks after initial injury.
bones were exposed on the right lower extremity. On initial exam, bilateral pedal pulses were present, and all toes had less than two second capillary refill. Sensation, motor, and strength were normal. During the 48-day-hospital stay, the patient had eight operations. There were weekly tangential excisional debridements of necrotic tissue with weekly application of one or more of the following placental allografts: dHACM, dHCM (Figure 2), dHUC (Figure 3), or mdHACM (Figure 4). The dHACM, dHCM and dHUC were used initially on both legs (week 2), then only on the right ankle (weeks 3 - 6). In addition, mdHACM was injected into the three exposed tendons of the right foot (weeks 4 - 5). When a wound infection needed to be treated, a combination of intravenous antibiotics and a topical antispetic wash such as hypochlorous acid (Vashe Wound Solution, UMNA, Fort Worth, Texas) was used.
Table 2 shows the usage protocol for the different placental allografts. Table 3 provides the features and application of each placental allograft product. Before each application of the placental allografts, exposed talar or tibial bone was tangentially trephined (top layer of bone was removed using a large “pineapple” drill bit in a hand-held burring device, to expose bone arteriolar bleeding. Normal saline prevented frictional heat with the burring. The exposed tendons were trimmed superficially with scissors to remove any desiccated tissue. Then, dHACM,
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Figure 2. Application of dHCM over the exposed tendons.
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Figure 3. Application of dHUC over the flexor digitorum longus tendon.
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Table 2. Weekly use of placental allografts on both legs and right foot.
*Placental Allografts: MIMEDX Group, Inc., Marietta, GA; L = left; R = right; NPWT = negative pressure wound therapy; STSG = split-thickness skin graft; tangential excision/debridement occurred twice on admission and on week 6.
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Figure 4. Injection of mdHACM the tibialis anterior tendon.
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Table 3. Placental allografts features and application on both legs and right foot.
*Placental Allografts: MIMEDX Group, Inc., Marietta, GA; NPWT = negative pressure wound therapy.
dHUC or dHCM was applied directly over the freshly trephined bone and the tendons. In addition, mdHACM was also injected into the tendons. Wound surfaces were covered with dressings made of petroleum gauze slathered with a hydrophilic ointment (Figure 5) followed by application of negative pressure wound therapy to bolster and promote healing (Figure 6). During the hospitalization, the patient underwent physical therapy to maintain strength and mobility in his feet and legs. At discharge for rehabilitation, 90% of the graft was viable over the right ankle joint, tendons and bone (Figure 1).
3. Discussion
The incorporation of four placental allografts (dHCM, dHACM, dHUC, and mdHACM) into this current limb salvage protocol preserved the extremity at risk for more invasive procedures—either a myocutaneous flap or amputation.
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Figure 5. Application of nonadherent dressing, 3% bismuth tribromophenate petrolatum dressing with a glycerol-hydroxyethyl cellulose lubricant.
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Figure 6. Application of negative pressure wound therapy with black granufoam over the nonadherent dressing.
Specifically, the addition of dHUC over the bone and mdHACM injections into tendons created an environment for adequate granulation tissue growth to receive and sustain STSG coverage and wound closure. It has been postulated, along with our own past anecdotal clinical experience, that granulation tissue growth over inflamed or scarred tendons is difficult to generate. However, injections of mdHACM successfully supported tendon preservation and granulation tissue growth in this case [13] .
A report about a viable, intact, and cryopreserved placental membrane (vCPM) (Grafix, Osiris Therapeutics, Columbia, MD) noted that seven (58%) patients of twelve had successful wound closure with tendon exposure (size 17.5, range 4 - 49 cm2) attached to or over a joint with an average eight (range 3 - 13 cm2) allograft applications [14] . The current patient had an acute burn injury with a much larger area of involvement (3100 cm2).
Ang and Chih-Kang have noted that placental membrane allografts aid in the “… normal healing cascade of hemostasis, inflammation, proliferation, and remodeling, … because tendon regeneration occurs through three main phases: inflammation, proliferation, and remodeling …” [15] . Fibroblast-induced scarring of the injured tendons can be reduced by placental membranes, because they contain hyaluronic acid, which dampens the upregulation of the biomarker, transforming growth factor-β (TGF-β), which triggers fibroblasts to undergo a phenotypical change to become myofibroblasts and contribute to the scarring and fibrosis during healing [15] .
4. Conclusion
In conclusion, the use of human placental allografts removed the necessity for myocutaneous flap coverage or an amputation of the right foot in this patient. mdHACM and dHUC were useful in covering the tendons with granulation tissue to form a bed for STSG coverage and adherence. A combination of placental allografts used to cover the wounds, deep tissue structures, and injectable products had a favorable impact in this patient’s limb salvage outcome (Figure 1). By avoidance of the physical, financial, and psychological burdens associated with more invasive procedures typically considered in the standard reconstructive ladder, a vital quality of life (limb retention) was also achieved for the patient [11] [12] .