Electrospun Microvasculature for Rapid Vascular Network Restoration

Abstract

Background:

Sufficient blood supply through neo-vasculature is a major challenge in cell therapy and tissue engineering in order to support the growth, function, and viability of implanted cells. However, depending on the implant size and cell types, the natural process of angiogenesis may not provide enough blood supply for long term survival of the implants, requiring supplementary strategy to prevent local ischemia. Many researchers have reported the methodologies to form pre-vasculatures that mimic in vivo microvessels for implantation to promote angiogenesis. These approaches successfully showed significant enhancement in long-term survival and regenerative functions of implanted cells, yet there remains room for improvement.

Methods:

This paper suggests a proof-of-concept strategy to utilize novel scaffolds of dimpled/hollow electrospun fibers that enable the formation of highly mature pre-vasculatures with adequate dimensions and fast degrading in the tissue.

Result:

Higher surface roughness improved the maturity of endothelial cells mediated by increased cell-scaffold affinity. The degradation of scaffold material for functional restoration of the neo-vasculatures was also expedited by employing the hollow scaffold design based on co-axial electrospinning techniques.

Conclusion:

This unique scaffold-based pre-vasculature can hold implanted cells and tissue constructs for a prolonged time while minimizing the cellular loss, manifesting as a gold standard design for transplantable scaffolds.

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References

  1. 1.

    Hamasaki N, Yamamoto M. Red blood cell function and blood storage. Vox Sang. 2000;79:191–7.

    CAS  Article  Google Scholar 

  2. 2.

    Hardy JD. Landmark perspective. Transplantation of blood vessels, organs, and limbs. JAMA. 1983;250:954–7.

    CAS  Article  Google Scholar 

  3. 3.

    Norton KA, Popel AS. Effects of endothelial cell proliferation and migration rates in a computational model of sprouting angiogenesis. Sci Rep. 2016;6:36992.

    CAS  Article  Google Scholar 

  4. 4.

    Jain RK, Au P, Tam J, Duda DG, Fukumura D. Engineering vascularized tissue. Nat Biotechnol. 2005;23:821–3.

    CAS  Article  Google Scholar 

  5. 5.

    Lovett M, Lee K, Edwards A, Kaplan DL. Vascularization strategies for tissue engineering. Tissue Eng Part B Rev. 2009;15:353–70.

    CAS  Article  Google Scholar 

  6. 6.

    Paulsen SJ, Miller JS. Tissue vascularization through 3D printing: will technology bring us flow? Dev Dyn. 2015;244:629–40.

    CAS  Article  Google Scholar 

  7. 7.

    Kaully T, Kaufman-Francis K, Lesman A, Levenberg S. Vascularization—the conduit to viable engineered tissues. Tissue Eng Part B Rev. 2009;15:159–69.

    CAS  Article  Google Scholar 

  8. 8.

    Kinstlinger IS, Miller JS. 3D-printed fluidic networks as vasculature for engineered tissue. Lab Chip. 2016;16:2025–43.

    CAS  Article  Google Scholar 

  9. 9.

    Lee JB, Wang X, Faley S, Baer B, Balikov DA, Sung HJ, et al. Development of 3D microvascular networks within gelatin hydrogels using thermoresponsive sacrificial microfibers. Adv Healthc Mater. 2016;5:781–5.

    CAS  Article  Google Scholar 

  10. 10.

    Awad NK, Niu H, Ali U, Morsi YS, Lin T. Electrospun fibrous scaffolds for small-diameter blood vessels: a review. Membranes (Basel). 2018;8:15.

    Article  Google Scholar 

  11. 11.

    Ravi S, Chaikof EL. Biomaterials for vascular tissue engineering. Regen Med. 2010;5:107–20.

    CAS  Article  Google Scholar 

  12. 12.

    Thottappillil N, Nair PD. Scaffolds in vascular regeneration: current status. Vasc Health Risk Manag. 2015;11:79–91.

    CAS  PubMed  PubMed Central  Google Scholar 

  13. 13.

    Costa-Almeida R, Granja PL, Soares R, Guerreiro SG. Cellular strategies to promote vasculaisation in tissue engineering applications. Eur Cells Mater. 2014;28:51–67.

    CAS  Article  Google Scholar 

  14. 14.

    Inomata K, Honda M. Co-culture of osteoblasts and endothelial cells on a microfiber scaffold to construct bone-like tissue with vascular networks. Materials (Basel). 2019;12:2869.

    CAS  Article  Google Scholar 

  15. 15.

    Perry L, Flugelman MY, Levenberg S. Elderly patient-derived endothelial cells for vascularization of engineered muscle. Mol Ther. 2017;25:935–48.

    CAS  Article  Google Scholar 

  16. 16.

    Song HG, Rumma RT, Ozaki CK, Edelman ER, Chen CS. Vascular tissue engineering: progress, challenges, and clinical promise. Cell Stem Cell. 2018;22:340–54.

    CAS  Article  Google Scholar 

  17. 17.

    Katsogiannis KAG, Vladisavljević GT, Georgiadou S. Porous electrospun polycaprolactone (PCL) fibres by phase separation. Eur Polym J. 2015;69:284–95.

    CAS  Article  Google Scholar 

  18. 18.

    Chung TW, Liu DZ, Wang SY, Wang SS. Enhancement of the growth of human endothelial cells by surfaceroughness at nanometer sca. Biomaterials. 2003;24:4655–61.

    CAS  Article  Google Scholar 

  19. 19.

    Birdsey GM, Shah AV, Dufton N, Reynolds LE, Almagro LO, Yang Y, et al. The endothelial transcription factor ERG promotes vascular stability and growth through Wnt/b-catenin signaling. Dev Cell. 2015;32:82–96.

    CAS  Article  Google Scholar 

  20. 20.

    Ferreri DM, Minnear FL, Yin T, Kowalczyk AP, Vincent PA. N-cadherin levels in endothelial cells are regulated by monolayer maturity and p120 availability. Cell Commun Adhes. 2008;15:333–49.

    CAS  Article  Google Scholar 

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Acknowledgements

This research was supported by National Research Fundation granted by the Korean Government (NRF-2015M3A9B3028685). We also thank the contribution of Mr. Eunmin Ko for technical help during qPCR and gene expression analysis.

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Correspondence to Jennifer H. Shin.

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Je-Hyun Han and Ung Hyun Ko are co-first authors.

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Han, J., Ko, U.H., Kim, H.J. et al. Electrospun Microvasculature for Rapid Vascular Network Restoration. Tissue Eng Regen Med (2020). https://doi.org/10.1007/s13770-020-00292-2

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Keywords

  • Vascular tissue engineering
  • Human umbilical vein endothelial cells (HUVECs)
  • Electrospinning