Acellular Nipple Scaffold Development, Characterization, and Preliminary Biocompatibility Assessment in a Swine Model.

Background: The standard in nipple reconstruction remains the autologous skin flap. Unfortunately, the results are not satisfying, with up to 75% loss of nipple projection over time. Existing studies investigated the use of primates as a source of implants.

Exceeding the Limits of Static Cold Storage in Limb Transplantation Using Subnormothermic Machine Perfusion.

Background:  For 50 years, static cold storage (SCS) has been the gold standard for solid organ preservation in transplantation. Although logistically convenient, this preservation method presents important constraints in terms of duration and cold ischemia-induced lesions. We aimed to develop a machine perfusion (MP) protocol for recovery of vascularized composite allografts (VCA) after static cold preservation and determine its effects in a rat limb transplantation model.

Optimization of Ex Vivo Machine Perfusion and Transplantation of Vascularized Composite Allografts.

Background: Machine perfusion is gaining interest as an efficient method of tissue preservation of Vascularized Composite Allografts (VCA). The aim of this study was to develop a protocol for ex vivo subnormothermic oxygenated machine perfusion (SNMP) on rodent hindlimbs and to validate our protocol in a heterotopic hindlimb transplant model.

Methods: In this optimization study we compared three different solutions during 6 h of SNMP (n = 4 per group).

Dual Versus Single Oxygenated Hypothermic Machine Perfusion of Porcine Livers: Impact on Hepatobiliary and Endothelial Cell Injury.

Background: Hypothermic oxygenated machine perfusion (HOPE) reduces ischemia-reperfusion injury of donor livers and is increasingly used in clinical transplantation. However, it remains unclear whether perfusion via the portal vein alone (HOPE) or via both the portal vein and hepatic artery (dual HOPE or DHOPE) is superior.

Methods: Twelve porcine livers donated after circulatory death were randomized for 2 h of HOPE (n = 6) or DHOPE (n = 6), followed by 4 h of warm reperfusion with whole blood, to mimic transplantation.

Opposite acute potassium and sodium shifts during transplantation of hypothermic machine perfused donor livers.

Liver transplantation is frequently associated with hyperkalemia, especially after graft reperfusion. Dual hypothermic oxygenated machine perfusion (DHOPE) reduces ischemia/reperfusion injury and improves graft function, compared to conventional static cold storage (SCS). We examined the effect of DHOPE on ex situ and in vivo shifts of potassium and sodium.

Biliary Bicarbonate, pH, and Glucose Are Suitable Biomarkers of Biliary Viability During Ex Situ Normothermic Machine Perfusion of Human Donor Livers.

Background: Ex situ normothermic machine perfusion (NMP) can be used to assess viability of suboptimal donor livers before implantation. Our aim was to assess the diagnostic accuracy of bile biochemistry for the assessment of bile duct injury (BDI).

Methods: In a preclinical study, 23 human donor livers underwent 6 hours of end-ischemic NMP to determine biomarkers of BDI.

Elevated Plasma Levels of Cell-Free DNA During Liver Transplantation Are Associated With Activation of Coagulation.

Patients undergoing liver transplantation have complex changes in their hemostatic system, and the net effect of these changes appears to be a "rebalanced" hemostatic profile. Recently, a process called NETosis in which a neutrophil expels DNA and proteins that form a weblike structure, has been described as a mechanism of pathogen entrapment. Increasing evidence suggests a pivotal role for neutrophil extracellular traps (NETs) and their main component, cell-free DNA (cfDNA), in activation of coagulation.

Advances in machine perfusion, organ preservation, and cryobiology: potential impact on vascularized composite allotransplantation.

Purpose Of Review: In this review, we discuss novel strategies that allow for extended preservation of vascularized composite allografts and their potential future clinical implications for the field of vascularized composite allotransplantation (VCA).

Recent Findings: The current gold standard in tissue preservation - static cold preservation on ice - is insufficient to preserve VCA grafts for more than a few hours. Advancements in the field of VCA regarding matching and allocation, desensitization, and potential tolerance induction are all within reasonable reach to achieve; these are, however, constrained by limited preservation time of VCA grafts.

Plasma From Patients Undergoing Liver Transplantation Is Resistant to Anticoagulant Activity of Soluble Thrombomodulin.

Recombinant human soluble thrombomodulin (ART-123) is an anticoagulant and anti-inflammatory agent clinically used for treatment of disseminated intravascular coagulation. Preclinical studies have shown that ART-123 reduces hepatic ischemia/reperfusion. Although ART-123 may therefore have clinical benefit in orthotopic liver transplantation, the substantial alterations in the hemostatic system may complicate its use in this setting.

Hypothermic oxygenated machine perfusion reduces bile duct reperfusion injury after transplantation of donation after circulatory death livers.

Dual hypothermic oxygenated machine perfusion (DHOPE) of the liver has been advocated as a method to reduce ischemia/reperfusion injury (IRI). This study aimed to determine whether DHOPE reduces IRI of the bile ducts in donation after circulatory death (DCD) liver transplantation. In a recently performed phase 1 trial, 10 DCD livers were preserved with DHOPE after static cold storage (SCS; www.

Normothermic machine perfusion of donor livers without the need for human blood products.

Normothermic machine perfusion (NMP) enables viability assessment of donor livers prior to transplantation. NMP is frequently performed by using human blood products including red blood cells (RBCs) and fresh frozen plasma (FFP). Our aim was to examine the efficacy of a novel machine perfusion solution based on polymerized bovine hemoglobin-based oxygen carrier (HBOC)-201.

Oxygenated hypothermic machine perfusion after static cold storage improves endothelial function of extended criteria donor livers.

Background: Lack of oxygen and biomechanical stimulation during static cold storage (SCS) of donor livers compromises endothelial cell function. We investigated the effect of end-ischemic oxygenated hypothermic machine perfusion (HMP) on endothelial cell function of extended criteria donor (ECD) livers.

Methods: Eighteen livers, declined for transplantation, were transported to our center using static cold storage (SCS).

Activation of Fibrinolysis, But Not Coagulation, During End-Ischemic Ex Situ Normothermic Machine Perfusion of Human Donor Livers.

Background: Ex situ normothermic machine perfusion (NMP) can be performed after traditional static cold preservation to assess graft function and viability before transplantation. It is unknown whether this results in activation of coagulation and fibrinolysis, as may occur upon graft reperfusion in vivo.

Methods: Twelve donor livers declined for transplantation underwent 6 hours of end-ischemic NMP using a heparinized plasma-based perfusion fluid.

Ex Situ Normothermic Machine Perfusion of Donor Livers.

In contrast to conventional static cold preservation (0-4 °C), ex situ machine perfusion may provide better preservation of donor livers. Continuous perfusion of organs provides the opportunity to improve organ quality and allows ex situ viability assessment of donor livers prior to transplantation. This video article provides a step by step protocol for ex situ normothermic machine perfusion (37 °C) of human donor livers using a device that provides a pressure and temperature controlled pulsatile perfusion of the hepatic artery and continuous perfusion of the portal vein.