Enhanced hemocompatibility and rapid magnetic anastomosis of electrospun small-diameter artificial vascular grafts.

Background: Small-diameter (<6 mm) artificial vascular grafts (AVGs) are urgently required in vessel reconstructive surgery but constrained by suboptimal hemocompatibility and the complexity of anastomotic procedures. This study introduces coaxial electrospinning and magnetic anastomosis techniques to improve graft performance. Methods: Bilayer poly(lactide-co-caprolactone) (PLCL) grafts were fabricated by coaxial electrospinning to encapsulate heparin in the inner layer for anticoagulation. Magnetic rings were embedded at both ends of the nanofiber conduit to construct a magnetic anastomosis small-diameter AVG. Material properties were characterized by micromorphology, fourier transform infrared (FTIR) spectra, mechanical tests, in vitro heparin release and hemocompatibility. In vivo performance was evaluated in a rabbit model of inferior vena cava replacement. Results: Coaxial electrospinning produced PLCL/heparin grafts with sustained heparin release, lower platelet adhesion, prolonged clotting times, higher Young's modulus and tensile strength versus PLCL grafts. Magnetic anastomosis was significantly faster than suturing (3.65 ± 0.83 vs. 20.32 ± 3.45 min, p < 0.001) and with higher success rate (100% vs. 80%). Furthermore, magnetic AVG had higher short-term patency (2 days: 100% vs. 60%; 7 days: 40% vs. 0%) but similar long-term occlusion as sutured grafts. Conclusion: Coaxial electrospinning improved hemocompatibility and magnetic anastomosis enhanced implantability of small-diameter AVG. Short-term patency was excellent, but further optimization of anticoagulation is needed for long-term patency. This combinatorial approach holds promise for vascular graft engineering.

Fabrication of Decellularized Spleen Matrix Derived from Rats.

Liver transplantation is the primary treatment for end-stage liver disease. However, the shortage and inadequate quality of donor organs necessitate the development of alternative therapies. Bioartificial livers (BALs) utilizing decellularized liver matrix (DLM) have emerged as promising solutions. However, sourcing suitable DLMs remains challenging. The use of a decellularized spleen matrix (DSM) has been explored as a foundation for BALs, offering a readily available alternative. In this study, rat spleens were harvested and decellularized using a combination of freeze-thaw cycles and perfusion with decellularization reagents. The protocol preserved the microstructures and components of the extracellular matrix (ECM) within the DSM. The complete decellularization process took approximately 11 h, resulting in an intact ECM within the DSM. Histological analysis confirmed the removal of cellular components while retaining the ECM's structure and composition. The presented protocol provides a comprehensive method for obtaining DSM, offering potential applications in liver tissue engineering and cell therapy. These findings contribute to the development of alternative approaches for the treatment of end-stage liver disease.

Low Prognostic Nutritional Index Is Common and Associated with Poor Outcomes following Curative-Intent Resection for Gastro-Entero-Pancreatic Neuroendocrine Tumors.

INTRODUCTION: To investigate the impact of prognostic nutritional index (PNI) on short- and long-term outcomes of patients who underwent curative-intent resection for gastro-entero-pancreatic neuroendocrine tumors (GEP-NETs). METHODS: Patients with GET-NETs who underwent curative-intent resection were identified from a multi-center database. The prognostic impact of clinicopathological factors including PNI on post-operative outcomes were evaluated. A novel nomogram was developed and externally validated. RESULTS: A total of 2,099 patients with GEP-NETs were included in the training cohort; 255 patients were in the external validation cohort. Median PNI (n = 973) was 47.4 (IQR 43.1-52.4). At the time of presentation, 1,299 (61.9%) patients presented with some type of clinical symptom. Low-PNI (≤42.2) was associated with gastrointestinal symptoms, as well as nodal metastasis and distant metastasis (all p < 0.05). Patients with a low PNI had a higher incidence of severe (≥Clavien-Dindo grade IIIa: low PNI 24.9% vs. high PNI 15.4%, p = 0.001) and multiple (≥3 types of complications: low PNI 14.5% vs. high PNI 9.2%, p = 0.024) complications, as well as a worse overall survival (OS)(5-year OS, low PNI 73.7% vs. high PNI 88.5%, p < 0.001), and RFS (5-year RFS, low PNI 68.5% vs. high PNI 79.8%, p = 0.008) versus patients with high PNI (>42.2). A nomogram based on PNI, tumor grade and metastatic disease demonstrated excellent discrimination and calibration to predict OS in both the training (C-index 0.748) and two external validation (C-index 0.827, 0.745) cohorts. CONCLUSIONS: Low PNI was common and associated with worse short- and long-term outcomes among patients with GEP-NETs.

Regional anticoagulation magnetic artificial blood vessels constructed by heparin-PLCL core-shell nanofibers for rapid deployment of veno-venous bypass.

Veno-venous bypass (VVB) is necessary for maintaining hemodynamic and internal environment stabilities in complex liver surgeries. However, the current VVB strategies require systematic anticoagulation and are time-consuming, leading to unexpected complications. This study aims to overcome these limitations by using a novel magnetic artificial blood vessel constructed with heparin-PLCL core-shell nanofibers. Coaxial electrospinning was used to fabricate core-shell nanofibers with heparin encapsulated into the core layer. The microstructure, physical and chemical properties, hemocompatibility, and heparin release behavior were characterized. The regional anticoagulation magnetic artificial vessel was constructed with these nanofibers and used to perform VVB in a rat liver transplantation model for in vivo evaluation. The core-shell nanofibers appeared smooth and uniform without apparent defects. Fluorescence and TEM images indicated that heparin was successfully encapsulated into the core layer. In addition, the in vitro heparin release test presented a two-phase release profile, burst release at day 1 and sustained release from days 2 to 14, which resulted in better hemocompatibility. The VVB could be rapidly deployed in 3.65 ± 0.83 min by the magnetic artificial vessel without systemic anticoagulation. Moreover, the novel device could reduce portal pressure and abdominal organ congestion, protect intestinal function, and increase the survival rate of liver transplantation with a long anhepatic phase from 0 to 65%. In summary, VVB can be rapidly deployed using regional anticoagulation magnetic artificial blood vessels without systemic anticoagulation, which is promising for improving patient outcomes after complex liver surgery.

Immunomodulatory role of mesenchymal stem cell therapy in liver fibrosis.

Liver fibrosis is a fibrogenic and inflammatory process that results from hepatocyte injury and is characterized by hepatic architectural distortion and resultant loss of liver function. There is no effective treatment for advanced fibrosis other than liver transplantation, but it is limited by expensive costs, immune rejection, and postoperative complications. With the development of regenerative medicine in recent years, mesenchymal stem cell (MSCs) transplantation has become the most promising treatment for liver fibrosis. The underlying mechanisms of MSC anti-fibrotic effects include hepatocyte differentiation, paracrine, and immunomodulation, with immunomodulation playing a central role. This review discusses the immune cells involved in liver fibrosis, the immunomodulatory properties of MSCs, and the immunomodulation mechanisms of MSC-based strategies to attenuate liver fibrosis. Meanwhile, we discuss the current challenges and future directions as well.