Small Grafts Research Articles

Small-for-Size Syndrome: Systemic Review in a Porcine Experimental Model

The small-for-size syndrome (SFSS) is characterized by prolonged hyperbilirubinemia, coagulopathy, and/or encephalopathy caused by a small liver graft that cannot sustain the metabolic demands of the recipient after a partial liver transplant (PLT). Models of PLT in pigs are excellent for studying this syndrome. This review aimed to identify the different porcine models of SFSS in the literature and compare their technical aspects and therapeutics methods focused on portal inflow modulation (PIM). We performed a systematic review of the porcine experimental model and SFSS. The MEDLINE-PubMed, EMBASE, Cochrane Library, LILACS, and SciELO databases were electronically searched and updated until June 20, 2021. The MeSH terms used were ''ORGAN SIZE'' AND ''LIVER TRANSPLANTATION". Thirteen SFSS porcine models were reported. Four were performed with portocaval shunt to PIM and 3 with mesocaval shunt to PIM. A few studies focused on clinical therapeutics to PIM; a study described somatostatin infusion to avoid SFSS. Initially, studies on PIM showed its potentially beneficial effects without mentioning the minimum portal flow that permits liver regeneration. However, an excessive portal diversion could be detrimental to this process. The use of porcine models on SFSS resulted in a better understanding of its pathophysiology and led to the establishment of various types of portal modulation, surgical techniques with different complexities, and pharmaceutical strategies such as somatostatin, making clear that without reducing the portal vein pressure the outcomes are poor. With the improvement of these techniques, SFSS can be avoided.

Случай успешного хирургического лечения трофической язвы роговицы

Purpose. To present the results of clinical outcomes of modern high-tech surgical treatment of a patient with unilateral neurotrophic keratitis using layered keratoplasty, which helps to prevent the development of further irreversible complications. Material and methods. A 45-year-old patient, after a course of radiation therapy for a brain tumor with the development of numbness on the upper left-side of her face, conjunctiva and cornea underwent six months later cataract phacoemulsification with IOL implantation in the left eye. After 2 months the patient’s vision decreased significantly, the examination showed that she developed neurotrophic keratitis on the operated eye, followed by progression and transformation into a trophic corneal ulcer with descemetocele. Results. In order to prevent further complications in the form of corneal perforation, anterior deep layered keratoplasty with a small diameter graft was performed. Extremely slow epithelialization was noted, and therefore a successful and effective biopsy of the cornea with an amniotic membrane was carried out. Conclusion. Cataract extraction in patients after radiation therapy with further loss of corneal sensation is extremely risky and can lead to serious consequences, in particular, the development of neurotrophic keratitis and corneal trophic ulcers. The use of the surgical technique of anterior deep layered corneal transplantation is an effective method of treating trophic ulcers, and the technique of performing the operation has certain features compared to the classical technology and requires extensive experience of the surgeon. However, the use of this method of surgical treatment for corneal trophic ulcers with descemetocele due to neurotrophic keratitis developed on the basis of radiation therapy does not always lead to success. In this case, the additional use of the amniotic membr ane for therapeutic purposes contributed to the r elief of the pathological process, paving the way for subsequent surgical interventions to restore high visual acuity i n the future. Key words: radiation therapy, neurotrophic keratitis, trophic ulcer, anterior deep layered keratoplasty, amniotic membrane

Abstract 404: Basement Membrane Of Small Diameter Vascular Extracellular Matrix Scaffolds Modulate Human Endothelial Cell Quiescence

Chronic vascular diseases affect over 25 million patients in the U.S, alone. While non-invasive therapies are available, approximately 4.5 million individuals are estimated to require a vascular bypass annually, worldwide. Autologous vascular grafts remain the standard of care; yet the absence of a suitable donor vessel results in approximately one third of patients being ineligible for autologous grafting. “Off-the-shelf” alternatives have been proposed, but have had limited pre-clinical success, primarily due to graft failure via thrombosis. Thrombotic failure risk has been shown to be dramatically reduced by the formation of a luminal quiescent endothelial cell monolayer. Recently, our group engineered an unfixed, antigen-removed (AR) extracellular matrix (ECM) scaffold from bovine saphenous vein (SV) which is minimally immunogenic and avoids in vivo thrombosis. However, the mechanism by which AR-ECM SV scaffolds prevent thrombosis remains unknown. In this study, we utilized cell culture, immunofluorescence, and RNA-seq to assess the hypothesis that hAECs seeded on the basement membrane (BM) surface of AR-ECM SV scaffolds adopt a quiescent phenotype. Cells seeded on the BM surface proliferated and underwent significantly greater XY migration than those seeded on the non-BM surface. Additionally, unlike non-BM seeded cells, BM seeding resulted in quiescent hAEC phenotype (i.e., apical polarization of podocalyxin and adherence junction protein (i.e., cadherin and β-catenin) colocalization). Finally, the transcriptional phenotype of hAECs seeded on the BM surface was similar to cells treated with simvastatin (i.e. “quiescent”) and significantly different from those treated with TNFα (i.e. “activated”) (n=6/group), as assessed by gene set enrichment and t-SNE analysis. We conclude that seeding hAECs on the BM surface of AR-SV ECM scaffolds induces a favorable “quiescent” phenotype, while an unfavorable “activated” phenotype is avoided. Ultimately, these results show that the BM surface of AR-SV-ECM scaffolds possesses inherent characteristics which promote quiescent hAEC behavior and resultant vascular homeostasis and will help inform future pre-clinical studies of this novel small diameter vascular grafting biomaterial.

Portable three-dimensional imaging to monitor small volume enhancement in face, vulva, and hand: A comparative study

Multiple handheld three-dimensional (3D) systems are available on the market, but data regarding their use in detecting small volumes are limited. The aim of this study was to compare different portable 3D technologies in detecting small volumetric enhancement on a mannequin model and a series of patients. Five portable 3D systems (Artec Eva, Crisalix, Go!Scan, LifeViz Mini, and Vectra H1) were tested in a controlled environment with standardised volumes and in a clinical setting with patients undergoing small volume fat grafting to face, vulva, and hand. Accuracy was assessed with absolute and relative technical error measurement (TEM and rTEM); precision with intra- and inter-observer reliability (rp and ICC); and usability in clinical practice with the following parameters: portability, suitability of use in operating theatre/clinic, ease of use of hardware and software, speed of capture, image quality, patient comfort, and cost. All tested devices presented overall good accuracy in detecting small volumetric changes ranging from 0.5 to 4 cc. Structured-light laser scanners (Artec Eva and Go!Scan) showed high accuracy, but their use in clinical practice was limited by longer capture time, multiple wiring, and complex software for analysis. Crisalix was considered the most user-friendly, less bothering for patients, and truly portable, but its use was limited to the face because the software does not include vulva and hand. Three-dimensional technologies exploiting the principle of passive stereophotogrammetry such as LifeViz Mini and Vectra H1 were the most versatile for assessing accurately multiple body areas, representing overall the best long-term value for money. Therefore, 3D portable technology is a non-invasive, accurate, and reproducible method to assess the volumetric outcome after facial, vulval, and hand injectables. The choice of the 3D system should be based on the clinical need and resources available.

Clinical effects of free latissimus dorsi myocutaneous flap combined with artificial dermis and split-thickness skin graft in the treatment of degloving injury in lower extremity

Objective: To observe the clinical effects of free latissimus dorsi myocutaneous flap combined with artificial dermis and split-thickness skin graft in the treatment of degloving injury in lower limbs. Methods: A retrospective observational study was conducted. From December 2017 to December 2020, 8 patients with large skin and soft tissue defect caused by degloving injury in lower extremity were admitted to Ningbo No.6 Hospital, including 5 males and 3 females, aged from 39 to 75 years, with wound area of 25 cm×12 cm-61 cm×34 cm. The free latissimus dorsi myocutaneous flap with latissimus dorsi muscle in the width of 12-15 cm and flap area of 20 cm×8 cm-32 cm×8 cm was used to repair the skin and soft tissue defect of bone/tendon exposure site or functional area. The other defect was repaired with bilayer artificial dermis, and the flap donor site was sutured directly. After the artificial dermis was completely vascularized, the split-thickness skin graft from thigh was excised and extended at a ratio of 1∶2 to 1∶4 and then transplanted to repair the residual wound, and the donor site of skin graft was treated by dressing change. The survival of latissimus dorsi myocutaneous flap, artificial dermis, and split-thickness skin graft after operation was observed, the interval time between artificial dermis transplantation and split-thickness skin graft transplantation was recorded, and the healing of donor site was observed. The appearance and function of operative area were followed up. At the last outpatient follow-up, the sensory recovery of flap was evaluated by British Medical Research Council evaluation criteria, the flap function was evaluated by the comprehensive evaluation standard of flap in Operative Hand Surgery, the scar of lower limb skin graft area and thigh skin donor area was evaluated by Vancouver scar scale, and the patient's satisfaction with the curative effects was asked. Results: The latissimus dorsi myocutaneous flap survived in 6 patients, while the distal tip of latissimus dorsi myocutaneous flap was partially necrotic in 2 patient and was repaired by skin grafting after resection at split-thickness skin grafting. The artificial dermis survived in all 8 patients after transplantation. The split-thickness skin graft survived in 7 patients, while partial necrosis of the split-thickness skin graft occurred in one patient and was repaired by skin grafting again. The interval time between artificial dermis transplantation and split-thickness skin graft transplantation was 15-26 (20±5) d. The donor site of latissimus dorsi myocutaneous flap healed with linear scar after operation, and the thigh skin graft donor site healed with scar after operation. The patients were followed up for 6-18 (12.5±2.3) months. The color and elasticity of the flap were similar to those of the surrounding skin tissue, and the lower limb joint activity returned to normal. There was no increase in linear scar at the back donor site or obvious hypertrophic scar at the thigh donor site. At the last outpatient follow-up, the sensation of the flap recovered to grade S2 or S3; 3 cases were excellent, 4 cases were good, and 1 case was fair in flap function; the Vancouver scar scale score of lower limb skin graft area was 4-7 (5.2±0.9), and the Vancouver scar scale score of thigh skin donor area was 1-5 (3.4±0.8). The patients were fairly satisfied with the curative effects. Conclusions: In repairing the large skin and soft tissue defect from degloving injury in lower extremity, to cover the exposed bone/tendon or functional area with latissimus dorsi myocutaneous flap and the residual wound with artificial dermis and extended split-thickness skin graft is accompanied by harvest of small autologous flap and skin graft, good recovery effect of functional area after surgery, and good quality of healing in skin grafted area.

Tubular TPU/SF nanofibers covered with chitosan-based hydrogels as small-diameter vascular grafts with enhanced mechanical properties

Native grafts such as internal mammary artery and saphenous vein are the main choice for coronary artery bypass graft. However, due to the limitations associated with their availability and rapid failure caused by hyperplasia, small diameter tissue-engineered vascular grafts (TEVGs) with sufficient post-implantation patency are urgently demanded as artificial alternatives. In our previous work, we innovatively fabricated a bilayer vascular graft providing appropriate structural and biological properties using electrospinning and freeze-drying methods. It was proved that the mechanical properties of the proposed graft enhanced in comparison with using either of methods individually. Here, we adopted the same methods and incorporated an anticoagulant internal layer (inner diameter 4 mm), comprised of co-electrospun fibers of silk fibroin (SF) and heparinized thermoplastic polyurethane (TPU), and an external highly porous hydrogel fabricated by freeze-drying method. The electrospun layer exhibited strong mechanical properties including superior elastic modulus (4.92 ± 0.11 MPa), suture retention force (6.73 ± 0.83 N), elongation at break (196 ± 4%), and comparable burst pressure (1140 ± 12 mmHg) while the external hydrogel provided SMCs viability. The heparin was released in a sustain manner over 40 days, and the cytocompatibility and blood compatibility of scaffold were approved using MTT assay and platelet adhesion test. Thus, the proposed graft has a potential to be used as an artificial blood vessel scaffold for later in-vivo transplantation.

Prevention and Management of Small-for-Size Syndrome of Liver Transplantation

Small-for-size syndrome (SFSS) is a critical complication of partial liver transplantation, particularly in adult-to-adult living donor liver transplantation (ALDLT) using a small graft. Minimally required liver graft size for a successful ALDLT is classically 40% of a standard recipient’s liver volume or 0.8% of recipient body weight. Recent progress in perioperative care and technical improvement push the lower limit of safe graft size to 25% of the recipient’s standard liver volume or 0.6% of the graft versus recipient weight ratio although this is an ongoing debate. The clinical manifestations of SFSS include various symptoms and signs related to graft dysfunction and portal hypertension in patients with small grafts. The risk factors for SFSS include poor preoperative patient condition, including portal pressure, surgical techniques to reduce portal pressure, and graft quality and size. Hence, various approaches have been explored to modulate inflow and pressure to a small graft and to decrease the outflow block to alleviate this SFSS as well as the selection of a patient and graft. Additionally, recent research and efforts to prevent and treat SFSS are reviewed. (Ewha Med J 2022;45(2):29-34)

The crescendo pulse frequency of shear stress stimulates the endothelialization of bone marrow mesenchymal stem cells on the luminal surface of decellularized scaffold in the bioreactor

ABSTRACT A completely confluent endothelial cell (EC) monolayer is required to maintain proper vascular function in small diameter tissue-engineered vascular graft (TEVG). However, the most effective method for EC attachment to the luminal surface and formation of an entire endothelium layer that works in vitro remains a complicated challenge that requires urgent resolution. Although pulsatile flow has been shown to be better suited for the generation of functional endothelium, the optimal frequency setting is unknown. Several pulsatile flow frequencies were used to implant rat bone mesenchymal stem cells (MSC) into the lumen of decellularized porcine carotid arteries. The endothelium's integrity and cell activity were investigated in order to determine the best pulse frequency settings. The results showed that MSC were maximally preserved and exhibited maximal morphological changes with improved endothelialization performance in response to increased pulse stimulation frequency. Increased pulse frequency stimulation stimulates the expression of mechanoreceptor markers, cytoskeleton reorganization in the direction of blood flow, denser skeletal proteins fibronectin, and stronger intercellular connections when compared to constant pulse frequency stimulation. MSC eventually develops an intact endothelial layer with anti-thrombotic properties on the inner wall of the decellularized tubular lumen. Conclusion: The decellularized vessels retain the three-dimensional structure of the vasculature, have a surface topography suitable for MSC growth, and have good mechanical properties. By increasing the frequency of pulsed stimulation, MSC endothelialize the lumen of the decellularized vasculature. It is expected to have anti-thrombotic and anti-neointimal hyperplasia properties after implantation, ultimately improving the patency of TEVG.

Wharton’s Jelly–Mesenchymal Stem Cell–Engineered Conduit for Pulmonary Artery Reconstruction in Growing Piglets

Surgical treatment of congenital heart defects affecting the right ventricular outflow tract often requires complex reconstruction and multiple reoperations. With a randomized controlled trial, we compared a novel tissue-engineered small intestine submucosa-based graft for pulmonary artery reconstruction (seeded with mesenchymal stem cells derived from Wharton's Jelly) with conventional small intestine submucosa in growing piglets. Six months after implantation, seeded grafts showed integration with host tissues at cellular level and exhibited growth potential on transthoracic echocardiography and cardiovascular magnetic resonance. Our seeded graft is a promising biomaterial for pulmonary artery reconstruction in pediatric patients with right ventricular outflow tract abnormalities.

Truncated vascular endothelial cadherin enhances rapid endothelialization of small diameter synthetic vascular grafts

Complete and rapid endothelialization is critical to the long-term performance of synthetic vascular grafts. A fully formed endothelium is resistant to thrombosis and mitigates the development of neointimal hyperplasia, the dominant modes of acute and chronic graft failure, respectively. Significant research efforts aim to develop strategies which enhance graft endothelialization through the incorporation of surface ligands that promote the attachment and growth of endothelial cells. In native vessels these functions are regulated by the adhesion molecule vascular endothelial cadherin (VE-Cad). VE-Cad is exclusive to endothelial cells and possesses high self-affinity, forming homodimers with VE-Cad on adjacent endothelial cells. Leveraging this targeted binding ability, we developed a graft functionalization approach using a recombinant truncated form of VE-Cad (VEtr). VEtr contains only the domains responsible for self-interaction, recognition and adhesion. Using the plasma functionalization technique, plasma immersion ion implantation (PIII) technique we immobilize VEtr onto the surface of electrospun polycaprolactone (PCL). VEtr scaffolds achieved a nearly 2-fold increase in attachment and spreading, and a 2.5-fold increase in proliferation of human coronary artery endothelial cells (HCAECs) compared with control scaffolds in vitro. Following 14-day implantation in a mouse carotid artery model, VEtr grafts showed ∼90% CD31-positive endothelial coverage. The benefits of this enhanced endothelialization included an ∼88% reduction in fibrin deposition (early thrombosis) as well as ∼63% reduction in macrophage recruitment (early neointimal hyperplasia). These findings highlight VEtr functionalization as a promising approach for rapid graft endothelialization which may potentially improve the long-term performance of synthetic vascular grafts.

A novel small diameter nanotextile arterial graft is associated with surgical feasibility and safety and increased transmural endothelial ingrowth in pig

Globally, millions of patients are affected by myocardial infarction or lower limb gangrene/amputation due to atherosclerosis. Available surgical treatment based on vein and synthetic grafts provides sub-optimal benefits. We engineered a highly flexible and mechanically robust nanotextile-based vascular graft (NanoGraft) by interweaving nanofibrous threads of poly-L-lactic acid to address the unmet need. The NanoGrafts were rendered impervious with selective fibrin deposition in the micropores by pre-clotting. The pre-clotted NanoGrafts (4 mm diameter) and ePTFE were implanted in a porcine carotid artery replacement model. The fibrin-laden porous milieu facilitated rapid endothelization by the transmural angiogenesis in the NanoGraft. In-vivo patency of NanoGrafts was 100% at 2- and 4-weeks, with no changes over time in lumen size, flow velocities, and minimal foreign-body inflammatory reaction. However, the patency of ePTFE at 2-week was 66% and showed marked infiltration, neointimal thickening, and poor host tissue integration. The study demonstrates the in-vivo feasibility and safety of a thin-layered vascular prosthesis, viz., NanoGraft, and its potential superiority over the commercial ePTFE.Graphical

Transnasal Medial Canthopexy Supported with Autogenous Bone Graft: A New Method for Repair of Traumatic Telecanthus.

The medial canthus is an important structure to maintain the shape of the eye and assist in drainage of the lacrimal sac. Traumatic telecanthus is a difficult deformity to treat which involves both esthetic and functional aspects. Transnasal wiring remains the gold standard for repair of the medial canthal tendon (MCT) avulsion; however, it is often complicated by canthal drift, extrusion of wires, and in-fracture of the contralateral orbital bones from pressure by tied wires. In order to overcome traditional transnasal wiring technique pitfalls, this study proposes a transnasal wiring fixation method supported with a bone graft to treat patients presenting with telecanthus following complex nasoorbitoethmoid fractures. From December 2018 to October 2020, 12 patients with traumatic telecanthus underwent transnasal wiring fixation of the MCT supported with bone graft. The wire holding the MCT was delivered through a single hole to the contralateral side and secured to a small bone graft by passing the wire through 2 holes in the graft in a button-like fashion. Then the wire end is pulled again to the affected side through the same hole and the 2 wires ends are tightly twisted after setting the MCT posterior to the lacrimal crest. Restoration of the MCT to its normal position was achieved in all patients. There were no observed major complications. Only 2 cases of wound infection and 1 case of dacrocystitis were encountered, which settled with conservative management. The preoperative palpebral fissure width (mean: 28.33mm ± 2.188mm) was significantly lower than the postoperative palpebral fissure width (mean: 34.17mm ± 1.03mm) ( P< 0.05). This study introduces a modified technique of transnasal wiring fixation to restore palpebral shape and intercanthal distance. The proposed technique could eliminate most of the frequently observed complications of the traditional methods.

Medial plantar artery-based perforator and island flaps: a case series of applications in sole defects.

Soft tissue defects of the plantar foot pose a challenge to the reconstructive surgeon. The plantar region of the foot has a unique skin structure, which helps in its paramount functions of weight-bearing and providing protective sensation. It is best replaced with tissue of its own kind. The medial plantar artery (MPA) flap fulfils all the requirements of an ideal replacement for small-to-medium-sized defects in the mid plantar and heel region. This study describes our experience with MPA-based flaps for small-to-medium-sized defects of the plantar foot. The study was conducted in a tertiary referral hospital between April 2017 and March 2020 on patients who presented with defects on the mid plantar region and heel. MPA perforator (MPAP) flap or island flap were applied. The donor site was covered with split-thickness skin grafts. The study included 21 patients. MPAP flap was applied in nine patients and the island flap was applied in 12 patients. The mean age of the patients was 37.95 years and the mean flap size was 36.6cm2. All flaps survived well. In two patients, venous congestion developed which resolved spontaneously, while three patients had small graft loss which also healed with conservative treatment. All patients regained protective sensation within five months of flap coverage. Based on the MPA, both perforator and island flaps can be raised due to the fairly constant position of the perforators. These flaps have the advantage of robust vascularity with the replacement of identical tissue for weight-bearing functions along with acceptable aesthetic outcomes. Since they also have the added advantage of conferring sensation, they can be used as a primary option in cases of small-to-medium-sized plantar foot defects.

Treatment of upper eyelid third-degree burns by dispersed implantation of very small autologous columnar skin grafts: A pilot study of a new method

ObjectiveThis retrospective study compared the effectiveness of dispersed implantation of very small autologous columnar skin (SCS) grafts and full-thickness skin grafts (FTSGs) for treating upper eyelid third-degree burns. MethodsFourteen patients and 26 eyes with granulation tissue formed by third-degree upper eyelid burns were enrolled in the study from August 2017 to June 2020. The experimental group of 6 patients with 11 eyes was treated with SCS grafts. The control group of 8 patients with 15 eyes was treated with FTSGs. The survival rate of the grafts, healing time, SCS diameter, upper eyelid movement distance (ULMD), visual analogue scale (VAS) score for patient satisfaction, and Vancouver Scar Scale (VSS) score were evaluated. ResultsThe difference in the survival rate between the two groups was not statistically significant (P = 0.06). The ULMD and VAS scores in the experimental group were higher than those in the control group (P < 0.05). The healing time was longer in the experimental group than in the control group (P < 0.05). The VSS scores of the donor site and the skin grafting site in the experimental group were lower than those in the control group (P < 0.05). ConclusionUnlike classical skin grafts, SCS implantation surgery can restore the appearance of the upper eyelid, and there is no obvious scar at the donor site. This can be a viable alternative to traditional FTSGs with potential benefits

Frequency and risk factors of surgical complications in patients with locally advanced cervical esophageal cancer

Objective. Analyze the frequency and prognostic factors of complications in patients with locally advanced cervical esophageal cancer after pharyngolaryngoesophagectomy with simultaneous reconstruction of the defect.Material and methods. The retrospective study included patients with a verified locally advanced cervical esophageal cancer who were treated at the N. N. Petrov National Research Institute of Oncology in the period from 2009 to 2018, who underwent surgical treatment followed by chemoradiotherapy. The end point of the study was the frequency of postoperative complications.Results. Forty-eight patients were included in the study. All patients underwent laryngopharyngoesophagectomy with simultaneous reconstruction of the digestive tract. Forty-one patients (85.4 %) underwent the reconstructive stage using a narrow gastric stalk, and a wide gastric stalk and a small intestine graft were used in 5 (10.4 %) and 2 (4.2 %) patients, respectively. The average duration of the operation was 390 (337.5–525.0) minutes, the volume of blood loss was 300 (200–500) ml, and the average time of hospitalization and the patient’s stay in the intensive care unit was 21.5 (16.00–36.00) and 3 (1.000–6.75) days, respectively. Complications within 30 days after surgical treatment were observed in 54.1 % of patients, while anastomosis failure, fistula formation and pneumonia were observed in 22.9 %, 12.5 % and 18.8 % of cases, respectively. Factors slightly increasing the likelihood of pneumonia in the early postoperative period were: duration of surgery [OR = 1.0 (95 % CI: 1.00–1.01), p = 0.0131] and intraoperative blood loss [OR = 1.0 (95 % CI: 1.00–1.01), p = 0.0017].Conclusion. The overall complication rate after pharyngolaryngoesophagectomy with simultaneous repair of the defect by bioengineered graft was 54.1 %. Intraoperative blood loss and duration of surgery were associated with an increased risk of complications.

Novel reinforcement of corrugated nanofiber tissue-engineered vascular graft to prevent aneurysm formation for arteriovenous shunts in an ovine model

ObjectiveMany patients who require hemodialysis treatment will often require a prosthetic graft after multiple surgeries. However, the patency rate of grafts currently available commercially has not been satisfactory. Tissue engineering vascular grafts (TEVGs) are biodegradable scaffolds created to promote autologous cell proliferation and functional neotissue regeneration and, accordingly, have antithrombogenicity. Therefore, TEVGs can be an alternative prosthesis for small diameter grafts. However, owing to the limitations of the graft materials, most TEVGs are rigid and can easily kink when implanted in limited spaces, precluding future clinical application. Previously, we developed a novel corrugated nanofiber graft to prevent graft kinking. Reinforcement of these grafts to ensure their safety is required in a preclinical study. In the present study, three types of reinforcement were applied, and their effectiveness was examined using large animals. MethodsIn the present study, three different reinforcements for the graft composed of corrugated poly-ε-caprolactone (PCL) blended with poly(L-lactide-co-ε-caprolactone) (PLCL) created with electrospinning were evaluated: 1) a polydioxanone suture, 2) a 2-0 polypropylene suture, 3) a polyethylene terephthalate/polyurethane (PET/PU) outer layer, and PCL/PLCL as the control. These different grafts were then implanted in a U-shape between the carotid artery and jugular vein in seven ovine models for a total of 14 grafts during a 3-month period. In evaluating the different reinforcements, the main factors considered were cell proliferation and a lack of graft dilation, which were evaluated using ultrasound examinations and histologic and mechanical analysis. ResultsNo kinking of the grafts occurred. Overall, re-endothelialization was observed in all the grafts at 3 months after surgery without graft rupture or calcification. The PCL/PLCL grafts and PCL/PLCL grafts with a polydioxanone suture showed high cell infiltration; however, they had become dilated 10 weeks after surgery. In contrast, the PCL/PLCL graft with the 2-0 suture and the PCL/PLCL graft covered with a PET/PU layer did not show any graft expansion. The PCL/PLCL graft covered with a PET/PU layer showed less cell infiltration than that of the PCL/PLCL graft. ConclusionsReinforcement is required to create grafts that can withstand arterial pressure. Reinforcement with suture materials has the potential to maintain cell infiltration into the graft, which could improve the neotissue formation of the graft.

Female gender is associated with increased late luminal narrowing within the stent graft after thoracic endovascular aortic repair.

Luminal narrowing, suspected secondary to thrombus, occurs within stent grafts at an unclear incidence after thoracic endovascular aortic repair (TEVAR). The significance of this phenomenon has not been determined, nor have the risk factors for development of intragraft luminal narrowing. Small graft diameter is hypothesized to be a risk factor for the development of ingraft stenosis. A retrospective analysis was performed of a multicenter healthcare system including all patients who underwent TEVAR between July 2011 and July 2019 with at least 1year of subsequently available surveillance contrast-enhanced computed tomography imaging. Standard demographic, preoperative, intraoperative, and postoperative variables were collected. Measurements were obtained via direct off-line images from computed tomography scans. Patent intragraft diameters were compared with baseline and interval change values were normalized to time to follow-up. The primary outcome measure was annual rate of intragraft luminal narrowing. There were 208 patients who met the inclusion criteria (94 women, 114 men) with a median follow-up of 822days. The mean annual rate of percent intragraft diameter reduction was 10.5± 7.7% for women and 7.6± 5.6% for men (P= .0026). Multivariate analysis demonstrated female gender (P= .0283), preoperative diagnosis of hypertension (P= .0449), and need for coverage of the left subclavian artery (P= .0328) were all significant predictors of intragraft luminal narrowing. Small aortic diameters were not found to be associated independently with ingraft luminal narrowing nor was the concomitant use of antiplatelet or anticoagulation medications. Significant amounts of ingraft luminal narrowing, defined as a greater than 20% intragraft diameter decrease, were associated with an increased need for any reintervention, including for malperfusion, endoleak, and symptomatic aneurysm (P= .0249). Kaplan-Meier estimates demonstrated a significant gender-associated difference in high rates of intragraft luminal narrowing (P=.00189). In this analysis, female gender is shown to be a significant nonmodifiable risk factor for intragraft luminal narrowing after TEVAR. The development of this phenomenon is not benign; as such, these findings were associated with an increased need for reintervention. This finding may be attributable to differences in aortic compliance or gender-associated differences in coagulation pathways and merits further investigation. Surveillance after thoracic stent grafting must account for patient-specific variations in complication risk.

Luminal Administration of a Water-soluble Carbon Monoxide-releasing Molecule (CORM-3) Mitigates Ischemia/Reperfusion Injury in Rats Following Intestinal Transplantation.

Background.The protective effects of carbon monoxide (CO) against ischemia/reperfusion (IR) injury during organ transplantation have been extensively investigated. Likewise, CO-releasing molecules (CORMs) are known to exert a variety of pharmacological activities via liberation of controlled amounts of CO in organs. Therefore, we hypothesized that intraluminal administration of water-soluble CORM-3 during cold storage of intestinal grafts would provide protective effects against IR injury.Methods.Orthotopic syngeneic intestinal transplantation was performed in Lewis rats following 6 h of cold preservation in Ringer solution or University of Wisconsin solution. Saline containing CORM-3 (100 µmol/L) or its inactive counterpart (iCORM-3) was intraluminally introduced in the intestinal graft before cold preservation.Results.Histopathological analysis of untreated and iCORM-3–treated grafts revealed a similar erosion and blunting of the intestinal villi. These changes in the mucosa structure were significantly attenuated by intraluminal administration of CORM-3. Intestinal mucosa damage caused by IR injury led to considerable deterioration of gut barrier function 3 h postreperfusion. CORM-3 significantly inhibited upregulation of proinflammatory mRNA levels, ameliorated intestinal morphological changes, and improved graft blood flow and mucosal barrier function. Additionally, CORM-3–treated grafts increased recipient survival rates. Pharmacological blockade of soluble guanylyl cyclase activity significantly reversed the protective effects conferred by CORM-3, indicating that CO partially mediates its therapeutic actions via soluble guanylyl cyclase activation.Conclusions.Our study demonstrates that luminally delivered CORM-3 provides beneficial effects in cold-stored rat small intestinal grafts and could be an attractive therapeutic application of CO in the clinical setting of organ preservation and transplantation.

Advances in liver transplantation for unresectable colon cancer liver metastasis.

It is estimated that 50% of patients with colorectal cancer will develop liver metastasis. Surgical resection significantly improves survival and provides a chance of cure for patients with colorectal cancer liver metastasis (CRLM). Increasing the resectability of primary unresectable liver metastasis provides more survival benefit for those patients. Considerable surgical innovations have been made to increase the resection rate and decrease the potential risk of hepatic failure postoperation. Liver transplantation (LT) has been explored as a potential curative treatment for unresectable CRLM. However, candidate selection criteria, chemotherapy strategies, refined immunity regimens and resolution for the shortage of grafts are lacking. This manuscript discusses views on surgical indication, peritransplantation anti-tumor and anti-immunity therapy and updated advances in LT for unresectable CRLM. A literature review of published articles and registered clinical trials in PubMed, Google Scholar, and Clinicaltrials.gov was performed to identify studies related to LT for CRLM. Some research topics were identified, including indications for LT for CRLM, oncological risk, antitumor regimens, graft loss, administration of anti-immunity drugs and solutions for graft deficiency. The main candidate selection criteria are good patient performance, good tumor biological behavior and chemosensitivity. Chemotherapy should be administered before transplantation but is not commonly administered posttransplantation for preventive purposes. Mammalian target of rapamycin regimens are recommended for their potential oncological benefit, although there are limited cases. In addition to extended criterion grafts, living donor grafts and small grafts combined with two-stage hepatectomy are efficient means to resolve organ deficiency. LT has been proven to be an effective treatment for selected patients with liver-only CRLM. Due to limited donor grafts, high cost and poorly clarified oncological risks, LT for unresectable CRLM should be strictly performed under a well-organized study plan in selected patients. Some vital factors, like LT indication and anti-tumor and anti-immune treatment, remain to be confirmed. Ongoing clinical trials are expected to delineate these topics.

Engineering the shape memory parameters of graphene/polymer nanocomposites through atomistic simulations: On the effect of nanofiller surface treatment

This paper aims to comprehend the mechanisms underlying the shape memory behavior of polylactic acid infused with graphene functionalized by four groups of –OH, –CH3, –NH2, and tethered polymer layer. Applying molecular dynamics simulation, it is revealed that the graphene surface treatment enhances the shape fixity ratio of nanocomposites monotonically by increasing the physical cross-linking points within the polymer matrix. The improvement would be even more pronounced by increasing the coverage degree of small functional groups and grafting density of the covalently bonded polymer chains. Monitoring the key parameters illustrates that contrary to the OH groups, which improve the shape recovery value, the other functional groups degrade it by prohibiting the polymer chains mobility. Attempts to explore the governing mechanism demonstrate that shape fixity is improved when the difference between the potential energy variations in the loading and unloading stages increases. Interestingly, shape recovery is only under the influence of conformational entropy, and it is not affected by the potential energy. As such, we also probe variations of the radius of gyration during the recovery stage to address the role of different functionalization procedures on the reported shape recovery parameter.