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International Journal of Nanomedicine · 2023 · IF 8

Experimental Investigation of Temperature Influence on Nanoparticle Adhesion in an Artificial Blood Vessel

Kai Yue,Chao Yang,Yu You,Xueying Wang,Xinxin Zhang

Background A good understanding of the adhesion behaviors of the nanocarriers in microvessels in chemo-hyperthermia synergistic therapy is conducive to nanocarrier design for targeted drug delivery.Methods In this study, we constructed an artificial blood vessel system using gelatins with a complete endothelial monolayer formed on the inner vessel wall. The numbers of adhered NPs under different conditions were measured, as well as the interaction forces between the arginine–glycine–aspartic acid (RGD) ligands and endothelial cells.Results The experimental results on the adhesion of ligand–coated nanoparticles (NPs) with different sizes and morphologies in the blood vessel verified that the gelatin-based artificial vessel possessed good cytocompatibility and mechanical properties, which are suitable for the investigation on NP adhesion characteristics in microvessels. When the temperature deviated from 37 °C, an increase or decrease in temperature resulted in a decrease in the number of adhered NPs, but the margination probability of NP adhesion increased at high temperatures due to the enhanced Brownian movement and flow disturbance. It is found that the effect of cooling was less than that of heating according to the observed changes in cell morphology and a decrease in cell activity under the static and perfusion culture conditions within the temperature range of 25 °C–43 °C. Furthermore, the measurement results of change in the RGD ligand-cell interaction with temperature showed good agreement with those in the number of adhered NPs.Conclusion The Findings suggest that designing ligands that can bind to the receptor and are least susceptible to temperature variation can be an effective means to enhance drug retention.

研究领域: 生物医学工程 · 纳米医学 · 细胞生物学
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EUROPEAN POLYMER JOURNAL · 2024 · IF 5.8

Antimicrobial peptide-based pH-responsive Polyvinyl alcohol hydrogel artificial vascular grafts with excellent antimicrobial and hematologic compatibility

Ying Liu,Qingyun Ma,Zhixuan Wang,Xinxin Shang,Yuting Lan,Guoping Guan,Lu Wang

Thrombosis and infection are the primary challenges limiting the clinical application of small-diameter artificial blood vessels. Numerous studies have focused on improving the hemocompatibility of artificial vascular materials, addressing properties such as anticoagulant activity, antithrombogenicity, low hemolysis rates, and reduced platelet adhesion. However, there has been comparatively less attention given to the antibacterial properties of these materials. This study utilizes polyester braided tubes and PVA/PAAm hydrogel materials, combined with surface modification techniques, to develop a pH-responsive antibacterial hydrogel artificial blood vessel graft. The hydrogel surface was grafted with a polymer brush hierarchical structure, and antimicrobial peptide MLT was immobilized to confer antibacterial properties. Additionally, 2,3-dimethylmaleic anhydride (DMMA) was covalently attached as a shielding group to achieve an environment-responsive strategy. The research demonstrates that this artificial blood vessel graft exhibits structural stability, excellent mechanical properties, and good cellular and hemocompatibility. Furthermore, it exhibits pH-responsive capabilities, triggering efficient antibacterial activity in low pH environments. The modified antibacterial hydrogel artificial blood vessel material shows low hemolysis rates, excellent anticoagulant properties, and reduced platelet adhesion. Therefore, the strategy of combining MLT with DMMA may effectively enhance the hemocompatibility and responsive antibacterial performance of artificial blood vessel materials.

研究领域: 生物医学工程 · 材料科学 · 组织工程
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Polymer Chemistry · 2017 ·Vol. 8 ·期 14 ·2266-2275 · IF 5.375

Mussel-inspired post-heparinization of a stretchable hollow hydrogel tube and its potential application as an artificial blood vessel

Jie Deng,Chong Cheng,Yingying Teng,Chuanxiong Nie,Changsheng Zhao

We report the fabrication of a highly stretchable hydrogel tube and its postfunctionalization for potential application as an artificial blood vessel. Although stretchable hydrogels have been well studied in the last decade, functionalization of the hydrogel remains a grand challenge because of the deterioration of its mechanical strength induced by the newly incorporated functional monomers. Herein, we use a mussel-inspired coating method to bestow the highly stretchable hydrogel with super hemocompatibility; meanwhile, the mechanical properties of the hydrogel matrix were not obviously damaged. Briefly, dopamine grafted heparin was anchored to an alginate/polyacrylamide double-network hydrogel via the mussel-inspired coating. The prolonged activated partial thromboplastin time (APTT), thrombin time (TT), and prothrombin time (PT) demonstrated the enhanced anticoagulant activity of the heparin functionalized hydrogl tube. The clotting time, platelet adhesion, hemolysis ratio, and complement activation results of the hydrogel indicated that the heparinized hydrogel tube has excellent hemocompatibility and can be used as an artificial blood vessel. Compared to the unmodified hydrogel, the heparinized hydrogel also shows an improved cell adhesion affinity towards blood endothelial cells. More importantly, after the mussel-inspired coating, the mechanical strength of the highly stretchable hydrogel tube can be retained. Thus, the obtained highly hemocompatible hollow hydrogel tube can meet the needs of the dynamic functionality of stretchable blood vessels as well as other highly elastic soft tissues.

研究领域: 生物材料 · 组织工程 · 血液动力学
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Frontiers in Bioengineering and Biotechnology · 2024 · IF 4.3

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

Liu Peng,Liu Xin,Yang Lifei,Qian Yerong,Lu Qiang,Shi Aihua,Wei Shasha,Zhang Xufeng,Lv Yi,Xiang Junxi

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.

研究领域: 生物医学工程 · 血管外科 · 材料科学
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ACS Applied Materials & Interfaces · 2022 · IF 10.383

Soft Biomimetic 3D Free-Form Artificial Vascular Graft Using a Highly Uniform Microspherical Porous Structure

Yuseok Kim,Chae Hwa Kim,Tae Hee Kim,Suk Hee Park

This study presents a biomimetic 3D customizable artificial vascular graft with a highly porous and uniform microscale structure. The structural features were obtained by dip coating of a highly close-packed microsphere suspension on a 3D printed sacrificial template. Considering the structured arrangement of microspherical porogens in the coating layer, the microsphere-leached constructs showed higher uniformity and porosity than the conventionally particulate-leached structures, leading to ultrasoft mechanical compliance. Considering biomechanical compatibility, the resulting elastic moduli were at the sub-MPa level, comparable with those of native vascular tissues. In addition, the developed porous graft was reinforced selectively at the edge regions using a nonporous coating to secure its practical sutureability for clinical use. The sufficiently low cytotoxicity was clinically confirmed to alleviate the stiffness mismatch issues at the anastomotic interface between the native tissue and the artificial graft, thus overcoming the relevant clinical complications. Furthermore, the overall superior properties could be implemented on the 3D printed template for patient-specific medicare, thus implying the manufacturability of patient-specific vascular grafts.

CAS / MDL: 8002-74-2
研究领域: 生物材料学 · 组织工程学 · 再生医学
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Biomaterials Science · 2022 ·Vol. 10 ·期 13 ·3559-3568 · IF 7.59

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

Peng Liu,Lifei Yang,Aihua Shi,Yerong Qian,Xin Liu,Dinghui Dong,Xufeng Zhang,Yi Lv,Junxi Xiang

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.

CAS / MDL: 920-66-1 25322-68-3
研究领域: 生物医学工程 · 材料科学 · 移植外科
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INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES · 2025 · IF 8.5

Three-dimensional customized artificial grafts functionalized with biomimetic softness and anticoagulant heparin-dopamine surface modification: Preclinical study for practical applications

Chae Hwa Kim,Yuseok Kim,Sandeep Karna,Sung Mook Yoo,Ju Han Lee,Yun Ju Kim,Jun Hyuk Lee,Won-Min Jo,Suk-Hee Park,Tae Hee Kim

Artificial vascular grafts, as blood vessel substitutes, are a prime challenge in tissue engineering and biomaterial research. An ideal artificial graft must have physiological and mechanical properties similar to those of a natural blood vessel, and hemocompatibility on its surface. We designed and fabricated artificial grafts by applying 3D printing and templated technology, which is endowed with morphologically patient-specific vascular reconstruction. To optimize mechanical properties, the graft wall was engineered with a controllable hybrid porous structure through a multilayer combination of porous and nonporous coatings, thereby achieving biomimetic mechanical flexibility with reduced stiffness. Further, we successfully synthesized Dopamine-conjugated heparin (Hep-DA) utilizing carbodiimide chemistry, and coated it on a 3D porous graft to improve both surface adhesion and anticoagulant ability. The Hep-DA-coated 3D graft did not show significant cytotoxic effects with a long-term sustained heparin release. We performed a preclinical study in swine using the developed graft along with commercially available graft ePTFE and Dacron as a reference. They were implanted in the swine aorta for 28 days and the implanted grafts were harvested for further analysis. Histopathology study results showed the feasibility of the developed artificial vascular grafts that have less calcification, fibrosis, and collagen deposition than commercially available grafts.

研究领域: 组织工程 · 生物材料科学 · 生物医学工程
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JOURNAL OF BIOMATERIALS APPLICATIONS · 2023 · IF 2.9

PLCL-TPU bi-layered artificial blood vessel with compliance matching to host vessel

Lihua Guan,Huijing Zhao,Kai Wang,Ke-qin Zhang,Kai Meng

Compliance mismatch between the artificial blood vessel and the host vessel leads to abnormal hemodynamics and is a major mechanical trigger of intimal hyperplasia. Efforts have been made to achieve higher compliance of artificial blood vessels. However, the preparation of artificial blood vessels with compliance matching to host vessels has not been realized. A bi-layered artificial blood vessel was successfully prepared by dip-coating and electrospinning composite method using poly(L-Lactide-co-caprolactone) (PLCL) and thermoplastic poly(ether urethane) (TPU). In the case of a certain wall thickness (200 μm), thickness ratios of the PLCL inner layer (dip-coating method) and TPU outer layer (electrospinning method) were controlled at 0:1, 1:9, 3:7, 5:5, 7:3, and 1:0 respectively and the compliance, radial tensile properties, burst pressure, and suture retention strength were investigated. Results showed compliance value of the artificial blood vessel decreased with the increase of the thickness ratio, which suggested the compliance of the bi-layered artificial blood vessel can be regulated by adjusting the ratio of the inner and outer layer thicknesses. In the six different artificial blood vessels, the one with thickness ratio of 1:9 not only had high compliance (8.768 ± 0.393%/100 mmHg) but also can guarantee the other mechanical properties, such as the radial breaking strength (6.333 ± 0.689 N/mm), burst pressure (534.473 ± 20.899 mmHg), and suture retention strength (300.773 ± 9.351 cN). The proposed artificial blood vessel preparation method is expected to achieve compliance matching with the host vessel. It is beneficial for eliminating abnormal hemodynamics and reducing intimal hyperplasia.

研究领域: 生物医学工程 · 材料科学 · 心血管外科
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JOURNAL OF MATERIALS SCIENCE-MATERIALS IN MEDICINE · 2022 ·Vol. 34 ·期 1 ·1-15 · IF 4.727

Tween-80 improves single/coaxial electrospinning of three-layered bioartificial blood vessel

Wu Chuang,Wang Haixiang,Cao Jin

Electrospinning is a promising technique for preparing bioartificial blood vessels. Nanofibers prepared by electrospinning can simulate the structure of extracellular matrix to promote cell adhesion and proliferation. However, thorn-like protrusions can appear as defects on electrospun scaffolds and coaxial electrospun nanofibers often have no clear core/shell structure, which can seriously affect the quality of bioartificial blood vessels. To address these problems, Tween 80 is added to the electrospinning solution, which results in a stable Taylor cone, eliminates the thorn-like protrusions on electrospun bioartificial blood vessels, and reduces interfacial effects due to different core/shell solutions during coaxial electrospinning. Simulations, biomechanical tests, and in vivo studies were performed. The results demonstrate the excellent mechanical properties and biocompatibility of the bioartificial blood vessel. This research provides a useful reference for optimizing the electrospinning process for fabricating bioartificial blood vessels. Graphical Abstract

研究领域: 组织工程学 · 生物材料科学 · 生物医学工程
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ACS Applied Materials & Interfaces · 2024 · IF 8.3

Dynamically Cross-Linked Double-Network Hydrogels with Matched Mechanical Properties and Ideal Biocompatibility for Artificial Blood Vessels

Xue Yi Jia,Can Feng Huang,Xi Meng,Dong Yu Zhu,Zhi Peng Chen,Tao Jiang,Yi Zi Zeng,Mao Sheng Xu

Vessel transplantation is currently considered the “gold standard” treatment for cardiovascular disease. However, ideal artificial vascular grafts should possess good biocompatibility and mechanical strength that match those of native autologous vascular tissue to promote in vivo tissue regeneration. In this study, a series of dynamic cross-linking double-network hydrogels and the resultant hydrogel tubes were prepared. The hydrogels (named PCO), composed of rigid poly(vinyl alcohol) (PVA), flexible carboxymethyl chitosan (CMCS), and a cross-linker of aldehyde-based β-cyclodextrin (OCD), were formed in a double-network structure with multiple dynamical cross-linking including dynamic imine bonds, hydrogen bonds, and microcrystalline regions. The PCO hydrogels exhibited superior mechanical strength, good network stability, and fatigue resistance. Additionally, it demonstrated excellent cell and blood compatibility. The results showed that the introduction of CMCS/OCD led to a significant increase in the proliferation rate of endothelial cells seeded on the surface of the hydrogel. The hemolysis rate in the test was lower than 0.3%, and both protein adsorption and platelet adhesion were reduced, indicating an excellent anticoagulant function. The plasma recalcification time test results showed that endogenous coagulation was alleviated to some extent. When formed into blood vessels and incubated with blood, no thrombus formation was observed, and there was minimal red blood cell aggregation. Therefore, this novel hydrogel tube, with excellent mechanical properties, exhibits antiadhesive characteristics toward blood cells and proteins, as well as antithrombotic properties, making it hold tremendous potential for applications in the biomedical and engineering fields.

CAS / MDL: 9002-89-5
研究领域: 生物医学工程 · 材料科学 · 组织工程
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ACS Applied Bio Materials · 2024 · IF 4.6

Bidirectional Elastic PTFE Small Diameter Artificial Blood Vessel Grafts and Surface Antithrombotic Functionalized Construction

Siqi Zhou,Yulu Liu,Xueke Yu,Dongfang Wang,Xiaofeng Wang,Qian Li

Expanded polytetrafluoroethylene (ePTFE) failed to achieve clinical application in the field of small-diameter blood vessels due to its lack of elasticity in the circumferential direction and high stiffness. Excellent multidirectional elasticity and dynamic compliance matching with natural blood vessels are important means to solve the problem of acute thrombosis and poor long-term patency. Herein, novel PTFE spinning blood vessels were prepared by the PTFE emulsion electrospinning process, which not only presented good bidirectional elasticity but also promoted the adhesion and proliferation of endothelial cells and induced the contractile expression of SMCs. And, a PTFE-shish and aminated polycaprolactone (PCL)-kebab structure has been developed that converted the chemically inert PTFE surface into a drug-loading platform for the multifunctionalization of PTFE vascular grafts. It provides novel preparation methods for the application of new bidirectional elastic small-diameter artificial blood vessels and their surface functionalization construction.

CAS / MDL: 50-78-2 25322-68-3
研究领域: 生物材料 · 组织工程 · 血管移植物 · 生物医学工程
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Journal of Materials Chemistry B · 2022 ·Vol. 10 ·期 16 ·3126-3137 · IF 7.571

Stiff and strong hydrogel tube with great mechanical properties and high stability in various solutions

Qiong Lv,Xingyue Sun,Lina Ye,Haiyi Liang

Hydrogel tubes are widely used in fields such as artificial blood vessels, drug delivery, biomedical scaffolds and cell adhesion, yet their application is often limited by unsatisfactory mechanical properties and poor stability in various solutions. Herein, a novel hydrogel tube exhibiting a remarkable mechanical performance and stability in various solutions is prepared by introducing a dual physically cross-linked double network (DN) hydrogel matrix. The obtained hydrogel tube can withstand ∼60 N load without fracture and be stretched to over twice its original length before and after immersing in various solutions. The great mechanical properties and stability in various solutions of hydrogel tubes are due to the introduction of a dual physically cross-linked poly(acrylamide-co-acrylic acid)/carboxymethylcellulose sodium/Fe3+ DN hydrogel, which possesses high elastic modulus (3.71 MPa), fracture energy (15.4 kJ m−2), and great stability in various solutions. In addition, the hydrogel tubes with different thickness, diameters, shapes and the multiple branched hydrogel tubes can also be fabricated to enable further functionalization for application requirements. Therefore, this new type of hydrogel tube presents tremendous potential for applications in biomedical and engineering fields.

CAS / MDL: 79-06-1 7647-14-5
研究领域: 生物医学工程 · 材料科学 · 组织工程
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