Small-diameter tissue-engineered vascular grafts are urgently needed for clinic arterial substitute. To simulate the structures and functions of natural blood vessels, we designed a novel triple-layer poly(ε-caprolactone) (PCL) fibrous vascular graft by combining E-jet 3D printing and electrospinning techniques. The resultant vascular graft consisted of an interior layer comprising 3D-printed highly aligned strong fibers, a middle layer made by electrospun densely fibers, and an exterior structure composed of mixed fibers fabricated by co-electrospraying. The biocompatible triple-layer graft was used for in vivo implantation, and results demonstrated that the longitudinally-aligned fibers within the lumen of the graft could enhance the proliferation and migration of endothelial cells, while maintained good mechanical properties. The exterior layer provided a pathway that encouraged cells to migrate into the scaffold after implantation. This experimental graft overcame the limitations of conventionally electrospun vascular grafts of inadequate porosity and lowly cell penetration. The unique structure of the triple-layer vascular graft promoted cell growth and infiltration in vivo, thus provided an encouraging substitute for in situ tissue engineering.
Here, 70 potential Vibrio pathogens belonging to nine species, dominated by Vibrio harveyi, were isolated and identified from diseased aquacultured marine fish in South China. Subsequently, the prevalence of 11 virulence genes and the resistance to 15 antibiotics in these strains were determined. Most strains possessed atypical virulence genes in addition to typical virulence genes. Notably, hflk and chiA originating from V. harveyi, and flaC associated with V. anguillarum were detected in more than 40% of atypical host strains. Multidrug resistance was widespread: 64.29% strains were resistant to more than three antibiotics, and the multi-antibiotic resistance index ranged from 0.00 to 0.60. The proportions of strains resistant to the antibiotics vancomycin, amoxicillin, midecamycin, and furazolidone all exceeded 50%; nevertheless, all strains were sensitive to florfenicol, norfloxacin, and ciprofloxacin. Furthermore, both virulence genes and antibiotic resistance were more prevalent in Hainan than in Guangdong, owing to the warmer climate and longer annual farming time in Hainan. These results therefore suggest that warming temperatures and overuse of antibiotics are probably enhancing antibiotic resistance and bacterial infection. This study reveals that pathogenic Vibrio spp. with multi-antibiotic resistance are highly prevalent among marine fish in South China and thus warrant further attention. The results will provide helpful guidance for ecological regulation and local antibiotic use in the control of marine fish farming' Vibrio diseases in South China, facilitating the implementation of national green and healthful aquaculture.
Rationale: The tumor microenvironment (TME) determines tumor progression and affects clinical therapy. Its basic components include cancer-associated fibroblasts (CAFs) and tumor-associated endothelial cells (TECs), both of which constitute the tumor matrix and microvascular network. The ability to simulate interactions between cells and extracellular matrix in a TME in vitro can assist the elucidation of cancer growth and evaluate the efficiency of therapies. Methods: In the present study, an in vitro 3D model of tumor tissue that mimicked in vivo cell physiological function was developed using tumor-associated stromal cells. Colorectal cancer cells, CAFs, and TECs were co-cultured on 3D-printed scaffolds so as to constitute an extracellular matrix (ECM) that allowed cell processes such as adhesion, stemness, proliferation, and vascularization to take place. Normal stromal cells were activated and reprogrammed into tumor-related stromal cells to construct a TME of tumor tissues. Results: The activated stromal cells overexpressed a variety of tumor-related markers and remodeled the ECM. Furthermore, the metabolic signals and malignant transformation of the in vitro 3D tumor tissue was substantially similar to that observed in tumors in vivo . Conclusions: The 3D tumor tissue exhibited physiological activity with high drug resistance. The model is suitable for research studies of tumor biology and the development of personalized treatments for cancer.
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