Science China-Chemistry
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2015
·Vol. 58
·期 12
·1866-1874
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IF 1.695
Yu Yanyan,Guo Lei,Wang Wei,Wu Jina,Yuan Zhi
The ability to supply suitable blood vessel system is a major challenge for artificial thick tissue engineering. Angiogenesis is a key point during the process of microvascular formation. Many bioactive molecules such as extra cellular matrix (ECM) proteins and adhesion peptides derived from the ECM are applied to promote angiogenesis. In this work, two adhesion peptides, YIGSR and REDV, were selected to modify sodium alginate (ALG) to obtain YIGSR- and REDV-alginate conjugates (ALG-YIGSR, and ALG-REDV, respectively). We mixed the two peptide-conjugates together in a series of concentration ratios to prepare bioactive surfaces for in vitro studies and hydrogel scaffolds for in vivo studies. In vitro studies showed that surfaces modified with 1.09 pmol/mm 2 peptide had the best affinity to human umbilical vein endothelial cells (HUVECs) than that with high or low concentrations of peptides. In addition, surfaces modified with dual peptides could significantly promote HUVECs proliferation, where ALG-YIGSR:ALG-REDV at a mole ratio of 5:1 exhibited the best enhancement ability. Furthermore, the in vivo angiogenesis results demonstrated that hydrogel scaffolds composed of mixed ALG-YIGSR and ALG-REDV at the 5:1 ratio had angiogenic induction potential by stimulating new blood vessel formation, and showed higher blood vessel density than scaffolds composed of a single peptide. These results demonstrated that a mixed combination of peptide alginate conjugates could be a potential scaffold to stimulate and induce angiogenesis in tissue engineering applications.
研究领域:
生物材料学
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细胞生物学
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医学工程
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产品关联
DOI
高影响因子
COLLOIDS AND SURFACES B-BIOINTERFACES
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2017
·
IF 3.887
Bicui Wang,Wei Wang,Yanyan Yu,Yingxue Zhang,Jingwei Zhang,Zhi Yuan
Enhancing the affinity of scaffolds for endothelial cell (EC) is a crucial procedure for promoting angiogenesis in tissue engineering. In this work, to achieve stronger binding affinity with ECs, the peptide sequence REDV was conjugated onto gold nanoparticles (AuNPs) to construct a multivalent ligand ( c REDV). Then, the EC adhesion and proliferation were studied to determine ligand affinity for ECs in vitro . The results show that the c REDV-modified alginate ( c REDV-ALG) surface exhibited a selective adhesion to human umbilical vein endothelial cells (HUVECs) compared with NIH 3T3 cells. The average area of individual HUVEC that adhered to c REDV-ALG was approximately 2.27-fold higher than that adhered to the monovalent REDV-modified alginate (REDV-ALG) surface. Additionally, a superior ability to promote the proliferation of HUVECs compared to the REDV-ALG surface was demonstrated. In vivo angiogenic assays were also carried out to assess the effect of multivalent strategy on the vascularization of scaffolds. The results illustrated that c REDV-ALG could stimulate new vessel formation in the scaffold, and the blood vessel density was at least 20% higher than that observed with monovalent REDV-ALG with a similar degree of ligand substitution. These results demonstrated that a multivalent ligand strategy was beneficial for the vascularization of engineered tissues.
研究领域:
组织工程
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生物材料科学
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分子生物学
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DOI
高影响因子
Journal of Materials Chemistry B
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2015
·Vol. 3
·期 44
·8670-8683
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IF 4.726
Shaojun Yuan,Gordon Xiong,Fei He,Wei Jiang,Bin Liang,Simo Pehkonen,Cleo Choong
Microcarrier cell culture systems provide one of the most promising techniques for cell amplification due to their high surface area-to-volume ratio. In this study, biodegradable polycaprolactone (PCL) microspheres tethered with carboxylated poly(glycidyl methacrylate)–REDV conjugates were developed by a combination of surface-initiated atom transfer radical polymerization (ATRP) and azide–alkyne click chemistry as conducive microcarriers for rapid cell expansion of human umbilical vein endothelial cells (HUVECs). Azido-terminated poly(glycidyl methacrylate) (PGMA-N3) brushes were grafted onto the PCL microspheres by surface-initiated ATRP. Subsequent carboxylation of PGMA-N3 brushes was accomplished by azide–alkyne click reaction with hexynoic acid. REDV peptides were covalently conjugated to the pendent carboxyl groups on the side chain of carboxylated PGMA-COOH brushes via carbodiimide chemistry to enhance the cytocompatibility of the three-dimension (3D) PCL scaffolding system. Success in each functionalization step was ascertained by the measurement of attenuated total reflectance-Fourier transform infrared spectroscopy (ATR-FTIR), X-ray photoelectron spectroscopy (XPS), scanning electron microscopy (SEM) and wet laser particle size analysis. In vitro cell-loading assay of HUVECs demonstrated a significant improvement of cell adhesion and proliferation on the REDV-immobilized PCL microsphere surfaces, and a confluent layer of HUVECs was formed after 7 days of incubation. The highly biocompatible and transportable nature of functionalized PCL microcarriers offers significant potential as a cell expansion platform.
研究领域:
生物材料学
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细胞生物学
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组织工程
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产品关联
DOI
PubMed
高影响因子
Materials Science & Engineering C-Materials for Biological Applications
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2018
·
IF 5.08
Danyu Yao,Zhiyong Qian,Jin Zhou,Ge Peng,Gang Zhou,Haifeng Liu,Yubo Fan
Rapid neovascularization within scaffolds is critical for the regeneration of thick complex tissues. The surface immobilization of peptides and other active molecules have been explored to improve the vascularization capacity of implants. However, the rapid degradation of these molecules, the reaction conditions and cross-linking usually result in decreased vascularization capability. Here, we introduced a temperate, all-aqueous process to achieve bulk porous silk fibroin (SF) scaffolds. A temperature controlled process was used to induce the water stable structure by SF self-assembly. Arg-Glu-Asp-Val (REDV) peptides were added into SF solution and fixed within SF scaffolds during the self-assembly process. The results showed that the functionalized scaffolds markedly promoted the adhesion of endothelial cells in vitro . Moreover, the in vivo studies indicated enhanced cell infiltration in the bulk functionalized SF scaffolds and impressive vascularization at 4 weeks post-implantation. The functionalized scaffolds demonstrated excellent vascularization capability, providing an exciting biomaterial option for thick tissue regeneration.
研究领域:
生物材料
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组织工程
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再生医学
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产品关联
DOI
PubMed
高影响因子
ACS Applied Materials & Interfaces
·
2015
·
IF 6.723
Changcan Shi,Qian Li,Wencheng Zhang,Yakai Feng,Xiangkui Ren
Herein, we demonstrate that the REDV peptide modified nanoparticles (NPs) can serve as a kind of active targeting gene carrier to condensate pZNF580 for specific promotion of the proliferation of endothelial cells (ECs). First, we synthesized a series of biodegradable amphiphilic copolymers by ring-opening polymerization reaction and graft modification with REDV peptide. Second, we prepared active targeting NPs via self-assembly of the amphiphilic copolymers using nanoprecipitation technology. After condensation with negatively charged pZNF580, the REDV peptide modified NPs/pZNF580 complexes were formed finally. Due to the binding affinity toward ECs of the specific peptide, these REDV peptide modified NPs/pZNF580 complexes could be recognized and adhered specifically by ECs in the coculture system of ECs and human artery smooth muscle cells (SMCs) in vitro. After expression of ZNF580, as the key protein to promote the proliferation of ECs, the relative ZNF580 protein level increased from 15.7% to 34.8%. The specificity in actively targeting ECs of the REDV peptide conjugated NPs/pZNF580 complexes was still retained in the coculture system. These findings in the present study could facilitate the development of actively targeting gene carriers for the endothelialization of artificial blood vessels.
研究领域:
生物医学工程
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分子生物学
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纳米技术
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组织工程
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产品关联
DOI
PubMed
高影响因子
ARTIFICIAL ORGANS
·
2018
·Vol. 42
·期 8
·824-834
·
IF 2.111
Yaping Shan,Bing Jia,Ming Ye,Hua Shen,Weicheng Chen,Huifeng Zhang
Expanded polytetrafluoroethylene (ePTFE) prosthetic valves have been widely used in clinical applications in Asian countries. However, these valves still have limits with regard to thrombosis, neointimal hyperplasia, restenosis, and valvar vegetation. The achievement of in situ endothelialization on implant materials is a promising way to overcome those limits. Here, heparin/collagen multilayers were fabricated on ePTFE films via a layer-by-layer (LBL) self-assembly technique, and then, the endothelial cell (EC) adhesive peptide sequence Arg-Glu-Asp-Val (REDV) was immobilized on the multilayers. After modification with the heparin/collagen multilayers with or without REDV peptide, less platelet activation and aggregation were observed, the blood coagulation time was increased, and the hemolysis rate was decreased compared to that on pristine ePTFE films. The REDV-functionalized ePTFE films positively impacted early EC adhesion, later cell proliferation and cell activity. The EC barrier was confirmed to be successfully achieved on the functionalized ePTFE film surface in vitro. The successful assembly of the REDV-functionalized heparin/collagen multilayer on ePTFE films improved the blood compatibility, anticoagulant properties, and cell compatibility of the films in vitro, and thus, represents a candidate approach for applications requiring quick in situ endothelialization in vivo.
研究领域:
生物材料
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组织工程
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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
Journal of Materials Chemistry B
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2015
·Vol. 3
·期 16
·3379-3391
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IF 4.726
Haixia Wang,Yakai Feng,Jing Yang,Jintang Guo,Wencheng Zhang
Targeting gene engineering should be considered as an effective method for promoting endothelialization of vascular grafts. Herein, we developed a targeting REDV peptide functionalized polycationic gene carrier for carrying the pEGFP-ZNF580 plasmid with the aim of enhancing the transfection and migration capability of human endothelial cells. This polycationic gene carrier with the REDV peptide (mPEG-P(LA-co-CL)-PEI-REDV) was prepared by the conjugation of the Cys-Arg-Glu-Asp-Val-Trp (CREDVW) peptide with the amphiphilic block copolymer methoxy poly(ethylene glycol) ether-poly(L-lactide-co-ε-caprolactone)-poly(ethyleneimine) (mPEG-P(LA-co-CL)-PEI). mPEG-P(LA-co-CL)-PEI nanoparticles (NP) and mPEG-P(LA-co-CL)-PEI-REDV nanoparticles (REDV-NP) were formed by the self-assembly of the corresponding polycationic polymers, and then their pEGFP-ZNF580 complexes were prepared via the electrostatic interaction with pEGFP-ZNF580 plasmids, respectively. Gel electrophoresis results show that the targeted REDV-NPs could compress pEGFP-ZNF580 plasmids into stable complexes and protect the plasmids against desoxyribonuclease degradation. MTT assay indicates that these targeted REDV-NP/pEGFP-ZNF580 complexes exhibit better cyto-compatibility than the non-targeted NP/pEGFP-ZNF580 complexes and the control PEI 1800 Da/pEGFP-ZNF580 complexes. In vitro transfection experiments and western blot analysis of EA.hy926 endothelial cells show that the pEGFP-ZNF580 plasmid expression and the relative protein level transfected by targeted REDV-NP/pEGFP-ZNF580 complexes are roughly consistent with that transfected by PEI 25 kDa/pEGFP-ZNF580 complexes. More importantly, the scratch wound assay results demonstrate that the migration capability of EA.hy926 cells has been improved significantly by the expression of the pEGFP-ZNF580 plasmid. Our results indicate that the polycationic polymer with functional REDV peptides can be a potential candidate as a pEGFP-ZNF580 plasmid delivery carrier and may be used in the endothelialization of vascular grafts.
研究领域:
基因治疗
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生物医学工程
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组织工程
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产品关联
DOI
PubMed
高影响因子
Acta Biomaterialia
·
2019
·
IF 6.638
Yiyuan Duan,Shan Yu,Peifang Xu,Xuemei Wang,Xue Feng,Zhengwei Mao,Changyou Gao
Capture of endothelial progenitor cells (EPCs) in situ has been considered as a promising strategy for the rapid endothelialization and long-term patency of artificial blood vessels and implant devices. In this study, a CD133 + EPC capture surface was fabricated by grafting CD133 antibody (a more specific EPC surface marker than CD34) and Arg-Glu-Asp-Val (REDV) peptideon the methacrylate-grafted hyaluronic acid (MA-HA) and heparin-hybridized (MA-HA&Heparin) resisting layer. Vascular endothelial growth factor (VEGF) was further conjugated to the immobilized heparin. This engineered surface showed good hemocompatibility and significantly higher ability of capturing CD133 + EPCs from human peripheral blood mononuclear cells (PBMCs) and obviously upregulated the expression of endothelial cell (EC) marker genes of EPCs such as VEGF receptor 2 (VEGFR2), CD31 , VE-cadherin, and von Willebrand factor (vWF), facilitating the differentiation of EPCs into ECs. The dramatically enhanced EPC proliferation on this surface was dependent on the integrin-VEGFR synergistic signaling, as ERK1/2 phosphorylation was only significantly enhanced on the REDV and VEGF co-immobilized surface. This study highlights a new surface coating strategy for blood-contact materials based on the specific EPC capturing and rapid endothelialization. Statement of Significance Capture of endothelial progenitor cells (EPCs) in situ is a promising strategy for the rapid endothelialization and long-term patency of artificial blood vessels and scaffolds. More specific capture of EPCs by targeting CD133 rather than CD34 can better reduce the risk of inflammation and restenosis. On the other hand, an appropriate microenvironment for EPC proliferation is equally important for endothelialization, which is rarely considered by the existing EPC capture strategies. In this study, the capture ratio of EPCs was significantly increased by simultaneously grafting CD133 antibody and VEGF on a MA-HA and heparin-hybridized antifouling layer. Further, proliferation of EPCs after capture was significantly promoted by grafting VEGF and REDV peptide through the integrin–VEGFR synergistic signaling. This study highlights a new strategy for the surface coating of blood-contact materials based on specific EPC capture and rapid endothelialization.
研究领域:
生物医学工程
·
组织工程
·
细胞生物学
·
材料科学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Frontiers in Bioengineering and Biotechnology
·
2022
·
IF 6.064
Yaping Shan,Gang Chen,Qiqi Shi,Jiaxi Huang,Yaping Mi,Wenbo Zhang,Huifeng Zhang,Bing Jia
Prosthetic implants of expanded polytetrafluoroethylene (ePTFE) in the cardiovascular system have a high failure rate over the long term because of thrombosis and intimal hyperplasia. Although multiple surface modification methods have been applied to improve the anti-thrombotic and in situ endothelialization abilities of ePTFE, none have delivered outstanding results in vivo . Our previous study combined heparin/collagen multilayers and REDV peptides to modify ePTFE, and the in-vitro results showed that modification ePTFE with heparin/collagen-REDV can promote the cytocompatibility and antiplatelet property. This study illustrated the physical change, selective endothelial cells capture ability, and in vivo performance in further. The physical test demonstrated that this modification improved the hydrophilicity, flexibility and strength of ePTFE. A competition experiment of co-cultured endothelial cells and vascular smooth muscle cells verified that the heparin/collagen-REDV modification had high specificity for endothelial cell capture. A rabbit animal model was constructed to evaluate the in vivo performance of modified ePTFE implanted in the right ventricular outflow tract. The results showed that heparin/collagen-REDV modification was safe, promoted endothelialization, and successfully achieved regional anti-thrombosis without influencing body-wide coagulation function. The pathologic manifestations and mRNA expression pattern in tissues in contact with modified ePTFE indicated that this modification method may reduce M2-type macrophage infiltration and the expression of genes related to immune and inflammatory responses. The heparin/collagen-REDV modification may lower the incidence of complications related to ePTFE implantation and has good prospects for clinical use.
研究领域:
生物材料
·
心血管工程
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组织工程
·
生物医学工程
·
免疫学
✓ 已验证
DOI
PubMed
高影响因子
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