Heparinization and hybridization of electrospun tubular graft for improved endothelialization and anticoagulation

Yuan

Front. Bioeng. Biotechnol.

et al. 2023

Purpose: The absence of a complete endothelial cell layer is a well-recognized reason leading to small-diameter tissue-engineered vascular graft failure. Here we reported a multifunctional system consisting of chitosan (CS), Arg-Glu-Asp-Val (REDV) peptide, heparin, and vascular endothelial growth factor (VEGF) to achieve sustained anti-thrombosis and rapid endothelialization for decellularized and photo-oxidized bovine internal mammary arteries (DP-BIMA).Methods: CS-REDV copolymers were synthesized via a transglutaminase (TGase) catalyzed reaction. CS-REDV-Hep nanoparticles were formed by electrostatic self-assembly and loaded on the DP-BIMA. The quantification of released heparin and vascular endothelial growth factor was detected. Hemolysis rate, platelets adhesion, endothelial cell (EC) adhesion and proliferation, and MTT assay were performed in vitro. The grafts were then tested in a rabbit abdominal aorta interposition model for 3 months. The patency rates were calculated and the ECs regeneration was investigated by immunofluorescence staining of CD31, CD144, and eNOS antibodies.Results: The nanoparticle-VEGF system (particle size: 61.8 ± 18.3 nm, zeta-potential: +13.2 mV, PDI: .108) showed a sustained and controlled release of heparin and VEGF for as long as 1 month and exhibited good biocompatibility, a lower affinity for platelets, and a higher affinity for ECs in vitro. The nanoparticle-VEGF immobilized BIMA achieved 100% and 83.3% patency in a rabbit abdominal interposition model during 1 and 3 months, respectively, without any thrombogenicity and showed CD31, CD144, eNOS positive cell adhesion as early as 1 day. After 3 months, CD31, CD144, and eNOS positive cells covered almost the whole luminal surface of the grafts.Conclusion: The results demonstrated that the multifunctional nanoparticle-VEGF system can enhance the anti-thrombosis property and promote rapid endothelialization of small-diameter tissue-engineered vascular grafts. Utilizing nanoparticles to combine different kinds of biomolecules is an appropriate technology to improve the long-term patency of small-diameter tissue-engineered vascular grafts.

Section: Discussionmentioning

confidence: 99%

Multifunctional nanoparticle-VEGF modification for tissue-engineered vascular graft to promote sustained anti-thrombosis and rapid endothelialization

Yuan

Front. Bioeng. Biotechnol.

et al. 2023

“…Zhang et al doped bacterial nanocellulose in electrospun cellulose acetate microfibers and then immobilized heparin on the inner surface of the fibers. 206 It was found that platelet adhesion was significantly reduced, and antithrombotic behavior was greatly enhanced on the vascular grafts loaded with heparin compared with other two groups of electrospun cellulose acetate microfibers and cellulose acetate microfibers doped with bacterial nanocellulose. The heparin showed a sudden release at the initial stage of implantation, resulting in lower levels of heparin release at later stages, which can be further improved.…”

Section: Vascular Tissue Regenerationmentioning

confidence: 97%

Electrospun nanofibers for manipulating soft tissue regeneration

et al. 2022

“…Additionally, biocompatibility of the CA/BNC graft was verified with both in vitro and in vivo biocompatibility assays. 43,160 Another modification that has been performed on the BNC to enhance its cell adhesion properties is the process of mercerization. This process involves the addition of an alkaline solution that transforms cellulose I to cellulose II.…”

Section: Structural Modificationsmentioning

confidence: 99%

Bacterial-Nanocellulose-Based Biointerfaces and Biomimetic Constructs for Blood-Contacting Medical Applications

et al. 2023

Understanding the interaction between biomaterials and blood is critical in the design of novel biomaterials for use in biomedical applications. Depending on the application, biomaterials can be designed to promote hemostasis, slow or stop bleeding in an internal or external wound, or prevent thrombosis for use in permanent or temporary medical implants. Bacterial nanocellulose (BNC) is a natural, biocompatible biopolymer that has recently gained interest for its potential use in blood-contacting biomedical applications (e.g., artificial vascular grafts), due to its high porosity, shapeability, and tissue-like properties. To promote hemostasis, BNC has been modified through oxidation or functionalization with various peptides, proteins, polysaccharides, and minerals that interact with the coagulation cascade. For use as an artificial vascular graft or to promote vascularization, BNC has been extensively researched, with studies investigating different modification techniques to enhance endothelialization such as functionalizing with adhesion peptides or extracellular matrix (ECM) proteins as well as tuning the structural properties of BNC such as surface roughness, pore size, and fiber size. While BNC inherently exhibits comparable mechanical characteristics to endogenous blood vessels, these mechanical properties can be enhanced through chemical functionalization or through altering the fabrication method. In this review, we provide a comprehensive overview of the various modification techniques that have been implemented to enhance the suitability of BNC for blood-contacting biomedical applications and different testing techniques that can be applied to evaluate their performance. Initially, we focused on the modification techniques that have been applied to BNC for hemostatic applications. Subsequently, we outline the different methods used for the production of BNC-based artificial vascular grafts and to generate vasculature in tissue engineered constructs. This sequential organization enables a clear and concise discussion of the various modifications of BNC for different blood-contacting biomedical applications and highlights the diverse and versatile nature of BNC as a natural biomaterial.