Surface modification of polycarbonate urethane by covalent linkage of heparin with a PEG spacer

Feng, Yakai; Tian, Hong; Tan, Mingqi; Zhang, Pengfei; Chen, Qingliang; Liu, Jianshi

doi:10.1007/s12209-013-1894-y

Cited by 10 publications

(7 citation statements)

References 33 publications

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“…Generally, PU surface was first treated with diisocyanates as coupling agents, using dibutyltin dilaurate (DBTDL) or Sn(Oct) 2 as a catalyst to introduce free isocyanate groups on the surface, and subsequently covalently grafting PEG via the reaction between the surface isocyanate groups and the hydroxyl groups of PEG. 271,272 Alternatively, in many other approaches, the hydroxyl groups of PEG were functionalized firstly by an end-capping reaction with HMDI or IPDI. 273,274 For example, IPDI reacted with star shaped PEG to yield isocyanate-terminated reactive stars.…”

Section: Surface Modification Of Artificial Vascular Grafts By Pegmentioning

confidence: 99%

“…26 A number of covalent immobilizing heparin strategies have been investigated and evaluated. 271,346 Generally, for the immobilization of heparin onto biomaterial surfaces, amine or carboxylic acid groups should be first introduced to serve as the anchoring groups. For example, a biomaterial surface was pretreated using the plasma technology and UV-induced graft polymerization with AAc.…”

Section: Surface Modification Of Artificial Vascular Grafts By Heparinmentioning

confidence: 99%

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Surface modification and endothelialization of biomaterials as potential scaffolds for vascular tissue engineering applications

et al. 2015

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Surface modification and endothelialization of vascular biomaterials are common approaches that are used to both resist the nonspecific adhesion of proteins and improve the hemocompatibility and long-term patency of artificial vascular grafts. Surface modification of vascular grafts using hydrophilic poly(ethylene glycol), zwitterionic polymers, heparin or other bioactive molecules can efficiently enhance hemocompatibility, and consequently prevent thrombosis on artificial vascular grafts. However, these modified surfaces may be excessively hydrophilic, which limits initial vascular endothelial cell adhesion and formation of a confluent endothelial lining. Therefore, the improvement of endothelialization on these grafts by chemical modification with specific peptides and genes is now arousing more and more interest. Several active peptides, such as RGD, CAG, REDV and YIGSR, can be specifically recognized by endothelial cells. Consequently, graft surfaces that are modified by these peptides can exhibit targeting selectivity for the adhesion of endothelial cells, and genes can be delivered by targeting carriers to specific tissues to enhance the promotion and regeneration of blood vessels. These methods could effectively accelerate selective endothelial cell recruitment and functional endothelialization. In this review, recent developments in the surface modification and endothelialization of biomaterials in vascular tissue engineering are summarized. Both gene engineering and targeting ligand immobilization are promising methods to improve the clinical outcome of artificial vascular grafts.

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Section: Surface Modification Of Artificial Vascular Grafts By Pegmentioning

confidence: 99%

Section: Surface Modification Of Artificial Vascular Grafts By Heparinmentioning

confidence: 99%

Surface modification and endothelialization of biomaterials as potential scaffolds for vascular tissue engineering applications

et al. 2015

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“…Recently, one particular polymer that has been electrospun to produce vascular grafts is polyurethane (18–20). Polyurethanes (PUs) possess excellent biocompatibility and more importantly mechanical properties, which make them ideal for vascular graft applications (21).…”

Section: Introductionmentioning

confidence: 99%

“…For example, we have previously shown that heparin-modified nanofibrous vascular grafts fabricated using biodegradable poly(L-lactide) (PLLA) exhibited higher patency and greater cell infiltration, suggesting that heparin may play multiple roles in maintaining function and promoting remodeling (36). Other chemical approaches to enable covalent conjugation of heparin using EDC chemistry range from bulk carboxylation of PU via bromoalkylation to the synthesis of PCU with pendant carboxyl groups or with PEG (20, 37, 38). In addition, recent findings on facile surface modification using mussel-inspired dopamine indicated that such passively adsorbed coating could not only enhance endothelial cell adhesion and viability but also immobilize biomolecules such as VEGF on the surface of vascular graft for accelerated endothelialization (39, 40).…”

Section: Introductionmentioning

confidence: 99%

End-point immobilization of heparin on plasma-treated surface of electrospun polycarbonate-urethane vascular graft

et al. 2017

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Small-diameter synthetic vascular grafts have high failure rate due to primarily surface thrombogenicity, and effective surface chemical modification is critical to maintain the patency of the grafts. In this study, we engineered a small-diameter, elastic synthetic vascular graft with off-the-shelf availability and anti-thrombogenic activity. Polycarbonate-urethane (PCU), was electrospun to produce nanofibrous grafts that closely mimicked a native blood vessel in terms of structural and mechanical strength. To overcome the difficulty of adding functional groups to PCU, we explored various surface modification methods, and determined that plasma treatment was the most effective method to modify the graft surface with functional amine groups, which were subsequently employed to conjugate heparin via end-point immobilization. In addition, we confirmed in vitro that the combination of plasma treatment and end-point immobilization of heparin exhibited the highest surface density and correspondingly the highest anti-thrombogenic activity of heparin molecules. Furthermore, from an in vivo study using a rat common carotid artery anastomosis model, we showed that plasma-heparin grafts had higher patency rate at 2 weeks and 4 weeks compared to plasma-control (untreated) grafts. More importantly, we observed a more complete endothelialization of the luminal surface with an aligned, well-organized monolayer of endothelial cells, as well as more extensive graft integration in terms of vascularization and cell infiltration from the surrounding tissue. This work demonstrates the feasibility of electrospinning PCU as synthetic elastic material to fabricate nanofibrous vascular grafts, as well as the potential to endow desired functionalization to the graft surface via plasma treatment for the conjugation of heparin or other bioactive molecules.

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“…Some biocompatible and hydrophilic biomaterials have been utilized for the surface modification of vascular grafts, for example, PEG [ 213 ], zwitterionic polymers [ 214 , 215 ]. PEG and zwitterionic polymers or groups can be directly coated [ 216 ], blended [ 217 , 218 ] or covalently grafted [ 213 , 219 ] on the scaffold surfaces, and the hydrophilic surfaces can effectively inhibit the protein adsorption and platelet adherence [ 214 , 220 ].…”

Section: Preventing Vascular Incidents For Long-term Lumen Patencymentioning

confidence: 99%

Challenges and strategies for in situ endothelialization and long-term lumen patency of vascular grafts

Zhang

Cheng

et al. 2021

Bioactive Materials

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Vascular diseases are the most prevalent cause of ischemic necrosis of tissue and organ, which even result in dysfunction and death. Vascular regeneration or artificial vascular graft, as the conventional treatment modality, has received keen attentions. However, small-diameter (diameter < 4 mm) vascular grafts have a high risk of thrombosis and intimal hyperplasia (IH), which makes long-term lumen patency challengeable. Endothelial cells (ECs) form the inner endothelium layer, and are crucial for anti-coagulation and thrombogenesis. Thus, promoting in situ endothelialization in vascular graft remodeling takes top priority, which requires recruitment of endothelia progenitor cells (EPCs), migration, adhesion, proliferation and activation of EPCs and ECs. Chemotaxis aimed at ligands on EPC surface can be utilized for EPC homing, while nanofibrous structure, biocompatible surface and cell-capturing molecules on graft surface can be applied for cell adhesion. Moreover, cell orientation can be regulated by topography of scaffold, and cell bioactivity can be modulated by growth factors and therapeutic genes. Additionally, surface modification can also reduce thrombogenesis, and some drug release can inhibit IH. Considering the influence of macrophages on ECs and smooth muscle cells (SMCs), scaffolds loaded with drugs that can promote M2 polarization are alternative strategies. In conclusion, the advanced strategies for enhanced long-term lumen patency of vascular grafts are summarized in this review. Strategies for recruitment of EPCs, adhesion, proliferation and activation of EPCs and ECs, anti-thrombogenesis, anti-IH, and immunomodulation are discussed. Ideal vascular grafts with appropriate surface modification, loading and fabrication strategies are required in further studies.

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Surface modification of polycarbonate urethane by covalent linkage of heparin with a PEG spacer

Cited by 10 publications

References 33 publications

Surface modification and endothelialization of biomaterials as potential scaffolds for vascular tissue engineering applications

Surface modification and endothelialization of biomaterials as potential scaffolds for vascular tissue engineering applications

End-point immobilization of heparin on plasma-treated surface of electrospun polycarbonate-urethane vascular graft

Challenges and strategies for in situ endothelialization and long-term lumen patency of vascular grafts

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