Novel Dynamic Organ Storage System Enhances Liver Graft Function in a Porcine Donation After Circulatory Death Model.

Donation after circulatory death (DCD) livers face increased risks of critical complications when preserved with static cold storage (SCS). Although machine perfusion (MP) may mitigate these risks, its cost and logistical complexity limit widespread application. We developed the Dynamic Organ Storage System (DOSS), which delivers oxygenated perfusate at 10°C with minimal electrical power requirement and allows real-time effluent sampling in a portable cooler.

Validation of Inter-Reader Agreement/Consistency for Quantification of Ellipsoid Zone Integrity and Sub-RPE Compartmental Features Across Retinal Diseases.

Background: An unmet need exists when clinically assessing retinal and layer-based features of retinal diseases. Therefore, quantification of retinal-layer-thicknesses/fluid volumes using deep-learning-augmented platforms to reproduce human-obtained clinical measurements is needed.

Methods: In this analysis, 210 spectral-domain optical coherence tomography (SD-OCT) scans (30 without pathology, 60 dry age-related macular degeneration [AMD], 60 wet AMD, and 60 diabetic macular edema [total 23,625 B-scans]) were included.

Capturing the Coverage Dependence of Aromatics' Adsorption through Mean-Field Models.

To capture the dominant interactions (surface-mediated and through-space) in catalytic hydrodeoxygenation systems, coverage-dependent mean-field models of aromatic adsorption are developed on Pt(111) and Ru(0001). We derive three key insights from this work: (1) we can universally apply mean-field models to capture the coverage-dependent behavior of oxygenated aromatics on transition-metal surfaces, (2) we can deconvolute surface-mediated and through-space interactions from the mean-field model, and (3) we can develop relatively accurate models that predict the adsorption energy of aromatics on transition-metal surfaces for the full coverage range using the work function at the lowest modeled coverage. Our approach enables the rapid prediction of the coverage-dependent behavior of oxygenated aromatics on transition-metal surfaces, reducing the computational cost associated with these studies by an order of magnitude.

Xenogeneic cross-circulation for physiological support and recovery of ex vivo human livers.

Background And Aims: The scarcity of suitable donor livers highlights a continuing need for innovation to recover organs with reversible injuries in liver transplantation.

Approach And Results: Explanted human donor livers (n = 5) declined for transplantation were supported using xenogeneic cross-circulation of whole blood between livers and xeno-support swine. Livers and swine were assessed over 24 hours of xeno-support.

Pulmonary artery banding in sheep: a novel large animal model for congestive hepatopathy.

Congestive hepatopathy is becoming increasingly recognized among Fontan-palliated patients. Elevated central venous pressure is thought to drive the pathologic progression, characterized by sinusoidal dilatation, congestion, and fibrosis. A clinically relevant large animal model for congestive hepatopathy would provide a valuable platform for researching novel biomarkers, treatment, and prevention.

Technique for xenogeneic cross-circulation to support human donor lungs ex vivo.

Background: Xenogeneic cross-circulation (XC) is an experimental method for ex vivo organ support and recovery that could expand the pool of donor lungs suitable for transplantation. The objective of this study was to establish and validate a standardized, reproducible, and broadly applicable technique for performing xenogeneic XC to support and recover injured human donor lungs ex vivo.

Methods: Human donor lungs (n = 9) declined for transplantation were procured, cannulated, and subjected to 24 hours of xenogeneic XC with anesthetized xeno-support swine (Yorkshire/Landrace) treated with standard immunosuppression (methylprednisolone, mycophenolate mofetil, tacrolimus) and complement-depleting cobra venom factor.

Large animal preclinical investigation into the optimal extracorporeal life support configuration for pulmonary hypertension and right ventricular failure.

Introduction: Right ventricular failure (RVF) is a major cause of mortality in pulmonary hypertension (PH). Mechanical circulatory support holds promise for patients with medically refractory PH, but there are no clinical devices for long-term right ventricular (RV) support. Investigations into optimal device parameters and circuit configurations for PH-induced RVF (PH-RVF) are needed.

Reactive oxygen species-degradable polythioketal urethane foam dressings to promote porcine skin wound repair.

Porous, resorbable biomaterials can serve as temporary scaffolds that support cell infiltration, tissue formation, and remodeling of nonhealing skin wounds. Synthetic biomaterials are less expensive to manufacture than biologic dressings and can achieve a broader range of physiochemical properties, but opportunities remain to tailor these materials for ideal host immune and regenerative responses. Polyesters are a well-established class of synthetic biomaterials; however, acidic degradation products released by their hydrolysis can cause poorly controlled autocatalytic degradation.

Noninvasive diffusion MRI to determine the severity of peripheral nerve injury.

Objective: Primary repair of peripheral nerves is recommended following transection; however, patient management following repair is challenged by a lack of biomarkers to nerve regeneration. Previous studies have demonstrated that diffusion magnetic resonance imaging (MRI) may provide viable biomarkers of nerve regeneration in injury models; though, these methods have not been systematically evaluated in graded partial transections and repairs.

Methods: Ex vivo diffusion MRI was performed in fixed rat sciatic nerve samples 4 or 12 weeks following partial nerve transection and repair (25% cut = 12, 50% cut = 12 and 75% cut = 11), crush injuries (n = 12), and sham surgeries (n = 9).

Cross-Circulation for Extracorporeal Liver Support in a Swine Model.

Although machine perfusion has gained momentum as an organ preservation technique in liver transplantation, persistent organ shortages and high waitlist mortality highlight unmet needs for improved organ salvage strategies. Beyond preservation, extracorporeal organ support platforms can also aid the development and evaluation of novel therapeutics. Here, we report the use of veno-arterial-venous (V-AV) cross-circulation (XC) with a swine host to provide normothermic support to extracorporeal livers.

A Large Animal Model for Pulmonary Hypertension and Right Ventricular Failure: Left Pulmonary Artery Ligation and Progressive Main Pulmonary Artery Banding in Sheep.

Decompensated right ventricular failure (RVF) in pulmonary hypertension (PH) is fatal, with limited medical treatment options. Developing and testing novel therapeutics for PH requires a clinically relevant large animal model of increased pulmonary vascular resistance and RVF. This manuscript discusses the latest development of the previously published ovine PH-RVF model that utilizes left pulmonary artery (PA) ligation and main PA occlusion.

Progression Toward Decompensated Right Ventricular Failure in the Ovine Pulmonary Hypertension Model.

Decompensated right ventricular failure (RVF) in patients with pulmonary hypertension (PH) is fatal, with limited treatment options. Novel mechanical circulatory support systems have therapeutic potential for RVF, but the development of these devices requires a large animal disease model that replicates the pathophysiology observed in humans. We previously reported an effective disease model of PH in sheep through ligation of the left pulmonary artery (PA) and progressive occlusion of the main PA.

Left Pulmonary Artery Ligation and Chronic Pulmonary Artery Banding Model for Inducing Right Ventricular-Pulmonary Hypertension in Sheep.

Pulmonary hypertension (PH) is a progressive disease that leads to cardiopulmonary dysfunction and right heart failure from pressure and volume overloading of the right ventricle (RV). Mechanical cardiopulmonary support has theoretical promise as a bridge to organ transplant or destination therapy for these patients. Solving the challenges of mechanical cardiopulmonary support for PH and RV failure requires its testing in a physiologically relevant animal model.

Xenogeneic cross-circulation for extracorporeal recovery of injured human lungs.

Patients awaiting lung transplantation face high wait-list mortality, as injury precludes the use of most donor lungs. Although ex vivo lung perfusion (EVLP) is able to recover marginal quality donor lungs, extension of normothermic support beyond 6 h has been challenging. Here we demonstrate that acutely injured human lungs declined for transplantation, including a lung that failed to recover on EVLP, can be recovered by cross-circulation of whole blood between explanted human lungs and a Yorkshire swine.

Author Correction: Probabilistic Assessment of Nerve Regeneration with Diffusion MRI in Rat Models of Peripheral Nerve Trauma.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

Diffusion Magnetic Resonance Imaging Predicts Peripheral Nerve Recovery in a Rat Sciatic Nerve Injury Model.

Background: Nerve regeneration after an injury should occur in a timely fashion for function to be restored. Current methods cannot monitor regeneration prior to muscle reinnervation. Diffusion tensor imaging has been previously shown to provide quantitative indices after nerve recovery.

Diffusion Tensor Tractrography Visualizes Partial Nerve Laceration Severity as Early as 1 Week After Surgical Repair in a Rat Model Ex Vivo.

Background: Previous studies in our laboratory have demonstrated that a magnetic resonance imaging method called diffusion tensor imaging (DTI) can differentiate between crush and complete transection peripheral nerve injuries in a rat model ex vivo. DTI measures the directionally dependent effect of tissue barriers on the random diffusion of water molecules. In ordered tissues such as nerves, this information can be used to reconstruct the primary direction of diffusion along fiber tracts, which may provide information on fiber tract continuity after nerve injury and surgical repair.

Probabilistic Assessment of Nerve Regeneration with Diffusion MRI in Rat Models of Peripheral Nerve Trauma.

Nerve regeneration after injury must occur in a timely fashion to restore function. Unfortunately, current methods (e.g.

Eosinophilic recruitment in thermally injured older animals is associated with worse outcomes and higher conversion to full thickness burn.

Background: Partial burn injury in older patients is associated with higher rates of morbidity, mortality, and conversion to full thickness burn (Finnerty et al., 2009; Pham et al., 2009).

Improving Strength and Quality of Epitendinous Repairs.

Epitendinous sutures not only join the 2 severed tendon edges but also supply strength and support to the repair. Multiple techniques have been described, but none of them include another thread of suture. This could potentially increase the strength of the repair without affecting gliding.

Burn wounds in the young versus the aged patient display differential immunological responses.

Background: Individuals in the geriatric age range are more prone than younger individuals to convert their partial thickness thermal burns into full thickness injuries. We hypothesized that this often observed clinical phenomenon is strongly related to differential local injury responses mediated by the immune system.

Materials & Methods: Skin samples from areas with partial thickness thermal burns were obtained during routine excision and grafting procedures between post burn days 2-6.

Assessment of the Effect of Autograft Orientation on Peripheral Nerve Regeneration Using Diffusion Tensor Imaging.

Purpose: Given no definite consensus on the accepted autograft orientation during peripheral nerve injury repair, we compare outcomes between reverse and normally oriented autografts using an advanced magnetic resonance imaging technique, diffusion tensor imaging.

Methods: Thirty-six female Sprague-Dawley rats were divided into 3 groups: sham-left sciatic nerve isolation without injury, reverse autograft-10-mm cut left sciatic nerve segment reoriented 180° and used to coapt the proximal and distal stumps, or normally oriented autograft-10-mm cut nerve segment kept in its normal orientation for coaptation. Animals underwent sciatic functional index and foot fault behavior studies at 72 hours, and then weekly.