Improved endothelial cell proliferation on laminin-derived peptide conjugated nanofibrous microtubes using custom made bioreactor

Year 2022, Volume: 6 Issue: 3, 220 - 226, 15.12.2022

Günnur Onak Pulat , Asena Gülenay Tatar Yusuf Hakan Usta , Ozan Karaman

https://doi.org/10.35860/iarej.1096616

Cited By: 1

Abstract

Cardiovascular diseases (CVD) are currently considered as one of the major reasons for death worldwide. The blockage of minor vessels such as the coronary arteries may be linked to more severe occurrences that might be fatal. The gold standard approach involves the transplantation of secondary vessels or the use of synthetic vascular grafts. Electrospun nanofiber (NF) based grafts produced with synthetic polymers might be simply modified to resemble the original structure of vessels providing desirable physical features and potentially improving cellular behavior including cell attachment, growth, and differentiation. Although poly lactic-co-glycolic acid (PLGA), is well-known, commercially available, degradable synthetic, has good mechanical and biocompatibility properties, PLGA is inadequate in terms of cell recognition signals. To overcome the bioactivity problem of PLGA, bioactive peptides are the most extensively utilized approach for surface modification. On the other hand, seeding and cultivation of tube-like conduits are challenging due to their shapes, and dynamic seeding and culture are considered beneficial for these grafts. Herein, we attempted to enhance the Endothelial Cells (ECs) attachment and proliferation on PLGA electrospun NF-based vascular grafts by both the conjugation of laminin-derived peptide IKVAV and perfusion culture with the custom-made bioreactor system. The bioreactor and its flow and pressure were simulated and decided using COMSOL Multiphysics 5.4. Human umbilical vein endothelial cell (HUVEC) adhesion and proliferation were increased by both functionalization of PLGA graft with IKVAV and using a custom-made perfusion bioreactor for cell seeding and cultivation within 7 days (d). This tubular vascular graft could be a potential tissue-engineered scaffold for the restoration of the venous system.

Keywords

Bioreactor, Electrospinning, Peptide, tissue engineering, vascular graft

Supporting Institution

TÜBİTAK (The Scientific and Technological Research Council of Turkey)

Project Number

2209-A University Students Research Projects Support Program

References

• 1. Levenson, J.W., P.J. Skerrett, and J.M. Gaziano, Reducing the global burden of cardiovascular disease: the role of risk factors. Prev Cardiol, 2002. 5(4): p. 188-99.
• 2. Obiweluozor, F.O., et al., Considerations in the Development of Small-Diameter Vascular Graft as an Alternative for Bypass and Reconstructive Surgeries: A Review. Cardiovascular Engineering and Technology, 2020. 11(5): p. 495-521.
• 3. Mikos, A.G. and J.S. Temenoff, Formation of Highly Porous Biodegradable Scaffolds for Tissue Engineering. Electronic Journal of Biotechnology, 2000. 3(2): p. 23-24.
• 4. Tallawi, M., et al., Strategies for the Chemical and Biological Functionalization of Scaffolds for Cardiac Tissue Engineering: a Review. Journal of the Royal Society, Interface, 2015. 12(108): p. 20150254-20150254.
• 5. Nakamura, M., et al., Construction of multi-functional extracellular matrix proteins that promote tube formation of endothelial cells. Biomaterials, 2008. 29(20): p. 2977-2986.
• 6. Agarwal, S., J.H. Wendorff, and A. Greiner, Use of electrospinning technique for biomedical applications. Polymer, 2008. 49(26): p. 5603-5621.
• 7. Karkan, S.F., et al., Electrospun nanofibers for the fabrication of engineered vascular grafts. Journal of Biological Engineering, 2019. 13(1): p. 83.
• 8. Ku, S.H. and C.B. Park, Human endothelial cell growth on mussel-inspired nanofiber scaffold for vascular tissue engineering. Biomaterials, 2010. 31(36): p. 9431-9437.
• 9. Kim, T.G. and T.G. Park, Biomimicking extracellular matrix: cell adhesive RGD peptide modified electrospun poly (D, L-lactic-co-glycolic acid) nanofiber mesh. Tissue engineering, 2006. 12(2): p. 221-233.
• 10. Nasseri, B.A., et al., Dynamic rotational seeding and cell culture system for vascular tube formation. Tissue engineering, 2003. 9(2): p. 291-299.
• 11. Hsu, S.-h., et al., The effect of dynamic culture conditions on endothelial cell seeding and retention on small diameter polyurethane vascular grafts. Medical Engineering & Physics, 2005. 27(3): p. 267-272.
• 12. Onak, G., U.K. Ercan, and O. Karaman, Antibacterial activity of antimicrobial peptide-conjugated nanofibrous membranes. Biomedical Materials, 2020. 16(1): p. 015020.
• 13. Zhao, Q., et al., Programmed Shape-Morphing Scaffolds Enabling Facile 3D Endothelialization. Advanced Functional Materials, 2018. 28: p. 1801027.
• 14. Hamsici, S., et al., Bioactive peptide functionalized aligned cyclodextrin nanofibers for neurite outgrowth. Journal of Materials Chemistry B, 2017. 5(3): p. 517-524.
• 15. Dicker, K.T., et al., Spatial Patterning of Molecular Cues and Vascular Cells in Fully Integrated Hydrogel Channels via Interfacial Bioorthogonal Cross-Linking. ACS Applied Materials & Interfaces, 2019. 11(18): p. 16402-16411.
• 16. Onak, G. and O. Karaman, Accelerated mineralization on nanofibers via non-thermal atmospheric plasma assisted glutamic acid templated peptide conjugation. Regen. Biomater., 2019. 6(4): p. 231-240.
• 17. Usta, Y.H., et al. Design of electrospinning collector for vascular tissue engineering applications. in 2017 Medical Technologies National Congress (TIPTEKNO). 2017.
• 18. Onak Pulat, G., et al., Role of functionalized self-assembled peptide hydrogels in in vitro vasculogenesis. Soft Matter, 2021. 17(27): p. 6616-6626.
• 19. Onak, G., et al., Aspartic and Glutamic Acid Templated Peptides Conjugation on Plasma Modified Nanofibers for Osteogenic Differentiation of Human Mesenchymal Stem Cells: A Comparative Study. Scientific Reports, 2018. 8(1): p. 17620.
• 20. Karaman, O., et al., Synergistic Effect of Cold Plasma Treatment and RGD Peptide Coating on Cell Proliferation over Titanium Surfaces. Tissue Engineering and Regenerative Medicine, 2018. 15(1): p. 13-24.
• 21. Best, C., et al., Toward a patient-specific tissue engineered vascular graft. Journal of tissue engineering, 2018. 9: p. 2041731418764709-2041731418764709.
• 22. Kent, K.C., et al., An in vitro model for human endothelial cell seeding of a small diameter vascular graft. ASAIO transactions, 1988. 34(3): p. 578-580.
• 23. Çelebi-Saltik, B., M.Ö. Öteyaka, and B. Gökçinar-Yagci, Stem cell-based small-diameter vascular grafts in dynamic culture. Connective Tissue Research, 2021. 62(2): p. 151-163.
• 24. Zhao, Q., et al., Programmed Shape-Morphing Scaffolds Enabling Facile 3D Endothelialization. Advanced Functional Materials, 2018. 28(29): p. 1801027.
• 25. Ali, S., et al., Immobilization of Cell-Adhesive Laminin Peptides in Degradable PEGDA Hydrogels Influences Endothelial Cell Tubulogenesis. BioResearch open access, 2013. 2(4): p. 241-249.
• 26. Grant, D.S., et al., Interaction of endothelial cells with a laminin A chain peptide (SIKVAV) in vitro and induction of angiogenic behavior in vivo. J Cell Physiol, 1992. 153(3): p. 614-25.
• 27. Grant, D.S. and Z. Zukowska, Revascularization of ischemic tissues with SIKVAV and neuropeptide Y (NPY). Angiogenesis, 2000: p. 139-154.