Wound Closure Outcomes Suggest Clinical Equivalency Between Lyopreserved and Cryopreserved Placental Membranes Containing Viable Cells

Ananian, Charles E.; Davis, RH; Johnson, Eric L.; Regulski, Matthew; Reyzelman, Alexander M.; Saunders, Molly; Danilkovitch, Alla

doi:10.1089/wound.2019.1028

Cited by 16 publications

(19 citation statements)

References 25 publications

(51 reference statements)

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“…They have collagen-rich extracellular matrix proteins, providing growth factors, glycosaminoglycans, fibroblasts and epithelial cells, and important mesenchymal stem cells. In vitro placental membranes promote cellular adhesion and migration, cell differentiation, and proangiogenic anti-inflammatory activities and protect growth factor function [ 155 , 156 ]. One randomized controlled trial evaluated dehydrated human placental allograft (dehydrated human amnion chorion membrane, dHACM) in patients with VLU [ 157 ].…”

Section: Clinical Aspectsmentioning

confidence: 99%

Why Venous Leg Ulcers Have Difficulty Healing: Overview on Pathophysiology, Clinical Consequences, and Treatment

Raffetto

Ligi

Maniscalco

et al. 2020

JCM

142

114

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Venous leg ulcers (VLUs) are one of the most common ulcers of the lower extremity. VLU affects many individuals worldwide, could pose a significant socioeconomic burden to the healthcare system, and has major psychological and physical impacts on the affected individual. VLU often occurs in association with post-thrombotic syndrome, advanced chronic venous disease, varicose veins, and venous hypertension. Several demographic, genetic, and environmental factors could trigger chronic venous disease with venous dilation, incompetent valves, venous reflux, and venous hypertension. Endothelial cell injury and changes in the glycocalyx, venous shear-stress, and adhesion molecules could be initiating events in VLU. Increased endothelial cell permeability and leukocyte infiltration, and increases in inflammatory cytokines, matrix metalloproteinases (MMPs), reactive oxygen and nitrogen species, iron deposition, and tissue metabolites also contribute to the pathogenesis of VLU. Treatment of VLU includes compression therapy and endovenous ablation to occlude the axial reflux. Other interventional approaches such as subfascial endoscopic perforator surgery and iliac venous stent have shown mixed results. With good wound care and compression therapy, VLU usually heals within 6 months. VLU healing involves orchestrated processes including hemostasis, inflammation, proliferation, and remodeling and the contribution of different cells including leukocytes, platelets, fibroblasts, vascular smooth muscle cells, endothelial cells, and keratinocytes as well as the release of various biomolecules including transforming growth factor-β, cytokines, chemokines, MMPs, tissue inhibitors of MMPs (TIMPs), elastase, urokinase plasminogen activator, fibrin, collagen, and albumin. Alterations in any of these physiological wound closure processes could delay VLU healing. Also, these histological and soluble biomarkers can be used for VLU diagnosis and assessment of its progression, responsiveness to healing, and prognosis. If not treated adequately, VLU could progress to non-healed or granulating VLU, causing physical immobility, reduced quality of life, cellulitis, severe infections, osteomyelitis, and neoplastic transformation. Recalcitrant VLU shows prolonged healing time with advanced age, obesity, nutritional deficiencies, colder temperature, preexisting venous disease, deep venous thrombosis, and larger wound area. VLU also has a high, 50–70% recurrence rate, likely due to noncompliance with compression therapy, failure of surgical procedures, incorrect ulcer diagnosis, progression of venous disease, and poorly understood pathophysiology. Understanding the molecular pathways underlying VLU has led to new lines of therapy with significant promise including biologics such as bilayer living skin construct, fibroblast derivatives, and extracellular matrices and non-biologic products such as poly-N-acetyl glucosamine, human placental membranes amnion/chorion allografts, ACT1 peptide inhibitor of connexin 43, sulodexide, growth factors, silver dressings, MMP inhibitors, and modulators of reactive oxygen and nitrogen species, the immune response and tissue metabolites. Preventive measures including compression therapy and venotonics could also reduce the risk of progression to chronic venous insufficiency and VLU in susceptible individuals.

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Section: Clinical Aspectsmentioning

confidence: 99%

Why Venous Leg Ulcers Have Difficulty Healing: Overview on Pathophysiology, Clinical Consequences, and Treatment

Raffetto

Ligi

Maniscalco

et al. 2020

JCM

142

114

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“…Grafix must be stored at À80°C before use and has a 3-year shelf life. 72,73 Given the cryopreservation, Grafix preserves the structural and cellular integrity of the amnion and chorion and is a true alternative to fresh placental membranes. 74 A multicenter, blinded randomized control trial found that by week 12, 62% of Grafix-treated DFU patients closed their wounds versus 21% of standard-of-care patients treated with surgical debridement and nonadherent dressings (p ¼ 0.0001).…”

Section: Cellular Skin Substitutesmentioning

confidence: 99%

“…A recent study found that patients treated with lyopreserved grafts averaged a wound closure rate of 59.2%, suggesting clinical equivalency to the cyropreserved counterpart. 73…”

Section: Cellular Skin Substitutesmentioning

confidence: 99%

Comparison of Skin Substitutes for Acute and Chronic Wound Management

et al. 2021

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Chronic and acute wounds, such as diabetic foot ulcers and burns, respectively, can be difficult to treat, especially when autologous skin transplantations are unavailable. Skin substitutes can be used as a treatment alternative by providing the structural elements and growth factors necessary for reepithelialization and revascularization from a nonautologous source. As of 2020, there are 76 commercially available skin substitute products; this article provides a review of the relevant literature related to the major categories of skin substitutes available.

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“…RCTs using cryopreserved and lyopreserved AM have shown a higher proportion of closure in the treatment of DFUs and faster closure compared with standard treatments in RCTs 16 . Using the lyopreserved construct, Ananian showed wound closure rates of 65.8% in DFU that had been present for <12 months with median time to closure of 63 days 17 …”

Section: Introductionmentioning

confidence: 99%

“…16 Using the lyopreserved construct, Ananian showed wound closure rates of 65.8% in DFU that had been present for <12 months with median time to closure of 63 days. 17 In this paper, we report the results of a bench study of cellular viability of cryo-and lyopreserved amniotic tissue samples and the clinical outcomes of a 12-week cohort study. The primary outcome of the study was the proportion of ulcers that achieved closure during treatment.…”

mentioning

confidence: 99%

Lyopreserved amniotic membrane is cellularly and clinically similar to cryopreserved construct for treating foot ulcers

Davis

Killeen

Farrar

et al. 2020

International Wound Journal

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We compared cellular viability between cryopreserved and lyopreserved amniotic membranes and clinical outcomes of the lyopreserved construct in a prospective cohort study of 40 patients with neuropathic foot ulcers. Patients received weekly application of lyopreserved membrane for 12 weeks with standard weekly debridement and offloading. We evaluated the proportion of foot ulcers that closed, time to closure, closure trajectories, and infection during therapy. We used chi-square tests for dichotomous variables and independent t-tests for continuous variables with an alpha of α = .10. Cellular viability was equivalent between cryo-and lyopreserved amniotic tissues. Clinically, 48% of subjects' wounds closed in an average of 40.0 days. Those that did not close were older (63 vs 59 years, P = .011) and larger ulcers at baseline (7.8 vs 1.6 cm 2 , P = .012). Significantly more patients who achieved closure reached a 50% wound area reduction in 4 weeks compared with non-closed wounds (73.7% vs 47.6%, P = .093). There was no difference in the slope of the wound closure trajectories between closed and non-closed wounds (0.124 and 0.159, P = .85), indicating the rate of closure was similar. The rate of closure was 0.60 mm/day (SD = 0.47) for wounds that closed and 0.50 mm/day (SD = 0.58) for wounds that did not close (P = .89).

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Wound Closure Outcomes Suggest Clinical Equivalency Between Lyopreserved and Cryopreserved Placental Membranes Containing Viable Cells

Cited by 16 publications

References 25 publications

Why Venous Leg Ulcers Have Difficulty Healing: Overview on Pathophysiology, Clinical Consequences, and Treatment

Why Venous Leg Ulcers Have Difficulty Healing: Overview on Pathophysiology, Clinical Consequences, and Treatment

Comparison of Skin Substitutes for Acute and Chronic Wound Management

Lyopreserved amniotic membrane is cellularly and clinically similar to cryopreserved construct for treating foot ulcers

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