BIOMATERIALS
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2024
·
IF 12.8
Mengxue Zhou,Zihao Wang,Mengyu Li,Qi Chen,Shengmin Zhang,Jianglin Wang
The development of small-diameter vascular grafts (SDVGs) still faces significant challenges, particularly in overcoming blockages within vessels. A key issue is the foreign-body response (FBR) triggered by the implants, which impairs the integration between grafts and native vessels. In this study, we applied an interfacial infiltration strategy to create a stable, hydrophilic, and passivated hydrogel coating on SDVGs. This coating effectively resisted FBR and improved integration between the grafts and host tissue. We also incorporated anthocyanins, an antioxidant, into the hydrogel network to mitigate oxidative stress and promote endothelialization. The hydrogel coating exhibited excellent stability, retaining its integrity during continuous flushing over 15 days. Anthocyanins were released in response to reactive oxygen species (ROS), reducing inflammation and enhancing vascularization in a mouse subcutaneous implantation model. In a rabbit carotid artery replacement model, the SDVGs exhibited rapid endothelialization, guided vascular remodeling, and inhibited calcification, showing strong potential for clinical application. This study presents a straightforward and effective approach to improve the patency rate, endothelialization, and anti-calcification properties of SDVGs by equipping them with a protective anti-FBR and anti-inflammation hydrogel layer.
研究领域:
生物医学工程
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组织工程
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材料科学
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DOI
PubMed
高影响因子
Biofabrication
·
2025
·Vol. 17
·期 4
·045013
·
IF 8
Wenxing Han,Hongguang Chen,Huan Chen,Yiran Xi,Dezhi Huang,Shanshan Yong,Yuanbo Zhou,Hui Liu,Chunli Zhang
This study aimed to improve the efficiency of decellularization and enhance the functional properties of vascular grafts to optimize their application in vascular repair. Rabbit abdominal aortas were used as the decellularization target, and ultrasound-assisted decellularization was performed using intermittent ultrasound at 100 W power, 20 kHz frequency, and 4 °C. Rabbit abdominal aortas were subjected to three different decellularization techniques. Based on comparative evaluation, ultrasound-assisted decellularization was implemented to enhance cell removal efficiency. In addition, dual-factor surface modification was performed using sodium heparin (HEP) and vascular endothelial growth factor 165 (VEGF165) to investigate anticoagulant and endothelialization potential. Ultrasound optimization enhanced decellularization efficiency by 1.5 times, increased matrix integrity to 85%, and decreased chemical residues by 30%. Dual-factor functionalization with HEP and VEGF165 improved anticoagulant properties by 40%, prolonged thrombus formation time by 45%, and enhanced endothelialization by 68%. In vivo animal studies demonstrated a 93% blood flow patency rate post-implantation, with superior tissue repair compared to the control group. This study presents an innovative approach that integrates ultrasound optimization and functional modification, addressing the limitations of traditional decellularization methods. It offers a high-performance, low-toxicity strategy for developing vascular grafts with significant clinical potential, particularly for small-diameter vascular applications.
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DOI
PubMed
高影响因子
INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
·
2023
·
IF 8.2
Shanzhu Guo,Yue Jiang,Jingjing Jiao,Yan Shi,Tao Zhu,Long Li
The spatial cellular alignment and multi-layer structure are vitally important for the physiological functions of natural blood vessels. However, the two features are difficult to be constructed in one scaffold simultaneously, especially in the small-diameter vascular scaffold. Here we report a general strategy to construct a gelatin-based biomimetic three-layer vascular scaffold with spatial alignment features mimicking the natural structure of blood vessels. By using a sequential electrospinning strategy combined with folding and rolling manipulation, a three-layer vascular scaffold with inner and middle layers spatially perpendicular to each other was obtained. The special features of this scaffold could fully mimic the natural multi-layer structures of blood vessels and also possess great potential for spatial arrangement guidance of corresponding cells in blood vessels.
研究领域:
组织工程
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生物材料
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生物医学工程
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DOI
PubMed
高影响因子
Bio-Design and Manufacturing
·
2020
·Vol. 4
·期 1
·72-86
·
IF 4.095
Xing Zheng,Zhao Chen,Zhang Chunchen,Fan Yubo,Liu Haifeng
For the surgical treatment of cardiovascular disease (CVD), there is a clear and unmet need in developing small-diameter (diameter < 6 mm) vascular grafts. In our previous work, sulfated silk fibroin (SF) was successfully fabricated as a potential candidate for preparing vascular grafts due to the great cytocompatibility and hemocompatibility. However, vascular graft with single layer is difficult to adapt to the complex internal environment. In this work, polycaprolactone (PCL) and sulfated SF were used to fabricate bilayer vascular graft (BLVG) to mimic the structure of natural blood vessels. To enhance the biological activity of BLVG, nicorandil (NIC), an FDA-approved drug with multi-bioactivity, was loaded in the BLVG to fabricate NIC-loaded BLVG. The morphology, chemical composition and mechanical properties of NIC-loaded BLVG were assessed. The results showed that the bilayer structure of NIC-loaded BLVG endowed the graft with a biphasic drug release behavior. The in vitro studies indicated that NIC-loaded BLVG could significantly increase the proliferation, migration and antioxidation capability of endothelial cells (ECs). Moreover, we found that the potential biological mechanism was the activation of PI3K/AKT/eNOS signaling pathway. Overall, the results effectively demonstrated that NIC-loaded BLVG had a promising in vitro performance as a functional small-diameter vascular graft.
研究领域:
生物医学工程
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心血管疾病
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组织工程
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产品关联
DOI
高影响因子
COMPOSITES PART B-ENGINEERING
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2025
·
IF 14.2
Jixia Deng,Changlin Zhai,Lei Zhan,Kuihua Zhang,Tao Yang,Qinfei Ke,Chen Huang,Anlin Yin
The long-term reliability of small-diameter vascular grafts (SDVGs) is still largely confined by acute thrombosis, intimal hyperplasia and delayed endothelialization. In this study, a fibrous SDVG containing both physical and biochemical cues was developed to promote rapid endothelialization. The success of our method depends on the integration of a bi-oriented luminal surface with the conjugation of salvianolic acid B (Sal B) via aminolysis and subsequent amidation reaction. Specifically, longitudinally aligned poly (lactide acid-co-ε-caprolactone) (PLCL) microfibers having nano-grooved surface texture provided bi-oriented topographical cues to guide the elongation and migration of endothelial cells (ECs), whilst the incorporation of Sal B served as a biochemical signal to inhibit thrombosis, enhance EC growth and increase von Willebrand factor (vWF) expression in ECs. When implanted into a rat abdominal aorta defect model, the graft was able to facilitate luminal EC coverage, smooth muscle cells infiltration and collagen deposition without causing stenosis or thrombosis. The combination of bi-oriented topography with surface functionalization may become a platform design to maintain patency and accelerate in situ tissue regeneration of SDVG.
研究领域:
生物材料学
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心血管医学
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组织工程学
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产品关联
DOI
高影响因子
INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
·
2021
·
IF 6.953
Pengfei Li,Dawei Jin,Jie Dou,Lijuan Wang,Yanfang Wang,Xingxing Jin,Xiao Han,Inn-Kyu Kang,Jiang Yuan,Jian Shen,Meng Yin
Rapid endothelialization and regulation of smooth muscle cell proliferation are crucial for small-diameter vascular grafts to address poor compliance, thromboembolism, and intimal hyperplasia, and achieve revascularization. As a gaseous signaling molecule, nitric oxide (NO) regulates cardiovascular homeostasis , inhibits blood clotting and intimal hyperplasia, and promotes the growth of endothelial cells. Due to the instability and burst release of small molecular NO donors, a novel biomacromolecular donor has generated increasing interest. In the study, a low toxic NO donor of S-nitrosated keratin (KSNO) was first synthesized and then coelectrospun with poly(ε-caprolactone) to afford NO-releasing small-diameter vascular graft. PCL/KSNO graft was capable to generate NO under the catalysis of ascorbic acid (Asc), so the graft selectively elevated adhesion and growth of human umbilical vein endothelial cells (HUVECs), while inhibited the proliferation of human aortic smooth muscle cells (HASMCs) in the presence of Asc. In addition, the graft displayed significant antibacterial properties and good blood compatibility. Animal experiments showed that the biocomposite graft could inhibit thrombus formation and preserve normal blood flow via single rabbit carotid artery replacement for 1 month. More importantly, a complete endothelium was observed on the lumen surface. Taken together, PCL/KSNO small-diameter vascular graft has potential applications in vascular tissue engineering with rapid endothelialization and vascular remolding.
研究领域:
生物材料学
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心血管医学
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组织工程学
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产品关联
DOI
PubMed
高影响因子
INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
·
2023
·
IF 8.2
Han Wang,Yonghao Xiao,Zhiping Fang,Yuanguo Zhang,Liu Yang,Chenyu Zhao,Zhu Meng,Yu Liu,Chongchong Li,Qianqian Han,Zengguo Feng
Cardiovascular disease has become one of the main causes of death. It is the common goal of researchers worldwide to develop small-diameter vascular grafts to meet clinical needs. Collagen is a valuable biomaterial that has been used in the preparation of vascular grafts and has shown good results. Recombinant humanized collagen (RHC) has the advantages of clear chemical structure, batch stability, no virus hazard and low immunogenicity compared with animal-derived collagen, which can be developed as vascular materials. In this study, Poly ( l -lactide- ε-caprolactone) with l -lactide/ε-caprolactone (PLCL) and type III recombinant humanized collagen (hCOLIII) were selected as raw materials to prepare vascular grafts, which were prepared by the same-nozzle electrospinning apparatus. Meanwhile, procyanidin (PC), a plant polyphenol, was used to cross-link the vascular grafts. The physicochemical properties and biocompatibility of the fabricated vascular grafts were investigated by comparing with glutaraldehyde (GA) crosslinked vascular grafts and pure PLCL grafts. Finally, the performance of PC cross-linked PLCL-hCOLIII vascular grafts were evaluated by rabbit carotid artery transplantation model. The results indicate that the artificial vascular grafts have good cell compatibility, blood compatibility, and anti-calcification performance, and can remain unobstructed after 30 days carotid artery transplantation in rabbits. The grafts also showed inhibitory effects on the proliferation of SMCs and intimal hyperplasia, demonstrating its excellent performance as small diameter vascular grafts.
研究领域:
生物材料
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组织工程
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血管外科
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生物医学工程
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产品关联
DOI
PubMed
高影响因子
Polymers
·
2022
·Vol. 14
·期 15
·3089
·
IF 4.967
Weijie Jiao,Chen Liu,Jingxin Shan,Zhiyuan Kong,Xiaohong Wang
Arterial stenosis or blockage is the leading cause of cardiovascular disease, and the common solution is to substitute the arteries by autologous veins or bypass the blood vessels physically. With the development of science and technology, arteries with diameter larger than 6 mm can be substituted by unbiodegradable polymers, such as polytetrafluoroethylene, clinically. Nevertheless, the construction of a small-diameter (less than 6 mm) artery with living cells has always been a thorny problem. In this study, a suit of combined mold was designed and forged for constructing small-diameter arterial vessels. Based on this combined mold, bioactive arterial vessels containing adipose-derived stem cells (ASCs) and different growth factors (GFs) were assembled together to mimic the inner and middle layers of the natural arteries. Before assembling, ASCs and GFs were loaded into a gelatin/alginate hydrogel. To enhance the mechanical property of the bilayer arterial vessels, polylactic–glycolic acid (PLGA) was applied on the surface of the bilayer vessels to form the outer third layer. The biocompatibility, morphology and mechanical property of the constructed triple-layer arterial vessels were characterized. The morphological results manifested that cells grow well in the gelatin/alginate hydrogels, and ASCs were differentiated into endothelial cells (ECs) and smooth muscle cells (SMCs), respectively. In addition, under the action of shear stress produced by the flow of the culture medium, cells in the hydrogels with high density were connected to each other, similar to the natural vascular endothelial tissues (i.e., endothelia). Especially, the mechanical property of the triple-layer arterial vessels can well meet the anti-stress requirements as human blood vessels. In a word, a small-diameter arterial vessel was successfully constructed through the combined mold and has a promising application prospect as a clinical small-diameter vessel graft.Keywords:small-diameter arterial vessels;adipose-derived stem cells (ASCs);combined mold;growth factors;gelatin/alginate hydrogels;polylactic–glycolic acid (PLGA)
研究领域:
组织工程
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生物材料
·
再生医学
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DOI
PubMed
高影响因子
ACS Nano
·
2025
·
IF 16
Chunliang Zhang,Chunyuan Wang,Ruitao Cha,Qinghua Meng,Zhan Hu,Yang Sun,Zulan Li,Min Xiao,Yan Zhang,Xingyu Jiang
Extracellular matrix (ECM)-based small-diameter vascular grafts (SDVGs, inner diameter (ID) < 6 mm) hold great promise for clinical applications. However, existing ECM-based SDVGs suffer from limited donor availability, complex purification, high cost, and insufficient mechanical properties. SDVGs with ECM-like structure and function, and good mechanical properties were rapidly prepared by optimizing common materials and preparation, which can improve their clinical prospects. Here, we rapidly prepared an electrospinning film-collagen/red blood cell membrane-genipin hydrogel tube (ES-C/Rm-G-ht, ID = 2 mm) by the combination of the cross-linking of genipin, plastic compression, electrospinning, and rolling without a biological adhesive, which had a shorter preparation time of less than 17 h compared to the existing ECM-based SDVGs (preparation time of 4–18 weeks). ES-C/Rm-G-ht exhibited a layered honeycomb-like structure and demonstrated the ECM-like functions to promote the proliferation and migration of endothelial cells, and prevent thrombus and inflammation. Furthermore, ES-C/Rm-G-ht, possessing sufficient mechanical strength, showed high patency, rapid endothelialization (95%), good regeneration of smooth muscle cell layers and ECM, and effective antistenosis capability after implantation in the rabbit’s carotid artery for 31 days. This work provides a straightforward, cost-effective, and promising strategy to prepare SDVGs with ECM-like structure and function, which is an ideal alternative for vascular grafts and autologous vessels in the current clinic.
研究领域:
组织工程
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生物材料
·
血管生物学
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再生医学
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生物医学工程
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产品关联
DOI
PubMed
高影响因子
Bioactive Materials
·
2020
·
IF 8.724
Zhiwen Zeng,Chengshen Hu,Qingfei Liang,Lan Tang,Delin Cheng,Changshun Ruan
Low patency ratio of small-diameter vascular grafts remains a major challenge due to the occurrence of thrombosis formation and intimal hyperplasia after transplantation. Although developing the functional coating with release of bioactive molecules on the surface of small-diameter vascular grafts are reported as an effective strategy to improve their patency ratios, it is still difficult for current functional coatings cooperating with spatiotemporal control of bioactive molecules release to mimic the sequential requirements for antithrombogenicity and endothelialization. Herein, on basis of 3D-printed polyelectrolyte-based vascular grafts, a biologically inspired release system with sequential release in spatiotemporal coordination of dual molecules through an electrostatic self-assembly was first described. A series of tubes with tunable diameters were initially fabricated by a coaxial extrusion printing method with customized nozzles, in which a polyelectrolyte ink containing of ε-polylysine and sodium alginate was used. Further, dual bioactive molecules, heparin with negative charges and Tyr-Ile-Gly-Ser-Arg (YIGSR) peptide with positive charges were layer-by-layer assembled onto the surface of these 3D-printed tubes. Due to the electrostatic interaction, the sequential release of heparin and YIGSR was demonstrated and could construct a dynamic microenvironment that was thus conducive to the antithrombogenicity and endothelialization. This study opens a new avenue to fabricate a small-diameter vascular graft with a biologically inspired release system based on electrostatic interaction, revealing a huge potential for development of small-diameter artificial vascular grafts with good patency.
研究领域:
生物材料
·
组织工程
·
生物医学工程
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产品关联
DOI
PubMed
高影响因子
Biomedical Materials
·
2024
·
IF 3.9
Yong-Hao Xiao,Xin Jin,Liujun Jia,Jubo Li,Baojie Zhang,Xue Geng,Lin Ye,Aiying Zhang,Yongquan Gu,Zeng-Guo Feng
In our previous study, the pristine bilayer small-diameter in situ tissue engineered vascular grafts (pTEVGs) were electrospun from a heparinized polycaprolactone (PCL45k) as an inner layer and a non-heparinized PCL80k as an outer layer in the thickness of about 131 μm and 202 μm, respectively. However, the hydrophilic enhancement of inner layer stemmed from the heparinization accelerated the degradation of grafts leading to the early formation of arterial aneury-sms in a period of 3 months, severely hindering the perennial observation of the neo-tissue regene-ration, host cell infiltration and graft remodeling in those implanted pTEVGs. Herein to address this drawback, the thickness of the outer layers was increased with PCL80k to around 268 μm, while the inner layer remained unchangeable. The thickened TEVGs named as tTEVGs were evaluated in six rabbits via a carotid artery interpositional model for a period of 9 months. All the animals kept alive and the grafts remained patent until explantation except for one whose one side of arterial blood vessels was occluded after an aneurysm occurred at 6 months. Although a significant degradation was observed in the implanted grafts at 9 month, the occurrence of aneurysms was obviously delayed compared to pTEVGs. The tissue stainings indicated that the endothelial cell remodeling was substantially completed by 3 months, while the regeneration of elastin and collagen remained smaller and unevenly distributed in comparison to autologous vessels. Additionally, the proliferation of macrophages and smooth muscle cells reached the maximum by 3 months. These tTEVGs possessing a heparinized inner layer and a thickened outer layer exhibited good patency and significantly delayed onset time of aneurysms.
研究领域:
组织工程
·
生物医学工程
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血管外科
·
材料科学
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DOI
PubMed
高影响因子
COLLOIDS AND SURFACES B-BIOINTERFACES
·
2023
·
IF 5.8
Kangjia Ding,Xueke Yu,Dongfang Wang,Xiaofeng Wang,Qian Li
Without differentiated inner and outer biological function, expanded polytetrafluoroethylene (ePTFE) small-diameter (<6 mm) artificial blood vessels would fail in vivo due to foreign body rejection, thrombosis, and hyperplasia. In order to synergistically promote endothelialization, anti-thrombogenicity, and anti-inflammatory function, we modified the inner and outer surface of ePTFE, respectively, by grafting functional biomolecules, such as heparin and epigallocatechin gallate (EGCG), into the inner surface and polyethyleneimine and rapamycin into the outer surface via layer-by-layer self-assembly. Fourier-transform infrared spectroscopy showed the successful incorporation of EGCG, heparin, and rapamycin. The collaborative release profile of heparin and rapamycin lasted for 42 days, respectively. The inner surface promoted human umbilical vein endothelial cells (HUVECs) adhesion and growth and that the outer surface inhibited smooth muscle cells growth and proliferation. The modified ePTFE effectively regulated the differentiation behavior of RAW264.7, inhibited the expression of proinflammatory mediator TNF-α, and up-regulated the expression of anti-inflammatory genes Arg1 and Tgfb-1. The ex vivo circulation results indicated that the occlusions and total thrombus weight of modified ePTFE was much lower than that of the thrombus formed on the ePTFE, presenting good anti-thrombogenic properties. Hence, the straightforward yet efficient synergistic surface functionalization approach presented a potential resolution for the prospective clinical application of small-diameter ePTFE blood vessel grafts.
研究领域:
生物医学工程
·
材料科学
·
组织工程
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产品关联
DOI
PubMed
高影响因子
危险品化学品经营许可证（带存储）