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Description
INTRODUCTION
Cardiovascular disease is one of the major causes of death worldwide [1]. Synthetic vascular grafts (SVG) and autograft vessels are the current treatment modalities but, are ineffective for vessels with a diameter lower than 6 mm due to compliance mismatch [2] and limited in both supply and anatomical variability, respectively. An alternative solution is via tissue engineered vascular grafts (TEVG) [2-3] which aim to match the mechanical and biological properties of native vessels [3].
Melt electrospinning writing (MEW) is a recently developed technique that allows for the layer by layer assembly of micron diameter fibres in highly organised architecture that can be tuned to mimic the collagen fibre orientations found in the native vessel wall [3]. Therefore, the aim of this project is the development of a VG able to overcome current limitations of compliance mismatch and poor endothelialisation causing clot formation.
METHODOLOGY
A custom-made MEW printer was used to direct the deposition of polymeric micron-scale fibres in a bioinspired direction. Different aspect ratios were investigated in planar conformation to better tune mechanical behaviour, cell alignment and matrix deposition, which was then translated into a tubular conformation, through the use of a rotating mandrel.
MEW bioinspired scaffolds were infiltrated with a lyophilised fibrinogen sponge functionalised with heparin to prevent clotting. This hybrid construct was further wrapped in an electrospun elastic PLCL sheath to seal the graft.
Scanning electron microscopy (SEM) was used to investigate morphological characteristics. Pore size, porosity and degradation rate of the fibrinogen was also assessed for different crosslinking agents. Ring tensile test was used to investigate the mechanical properties of the grafts and compare them to those of a native porcine tissue. Biological evaluation of cell behaviour and extra-cellular matrix (ECM) production were performed to identify the best aspect ratio. Hemocompatibility and endothelialisation assay were also performed to validate the use of this off-the-shelf VG.
RESULTS
Our data demonstrates a preferential alignment of cell as well as ECM deposition along the major diagonal. The presence of fibrinogen enhanced cell seeding efficiency and ECM production while not effecting alignment and orientation. Mechanical data reported a response that resembles the typical J-shape of native tissue. The addition of a highly elastic layer of electropsun PLCL allowed for a higher resistance in deformation and recovery, additionally, the permeability was improved. The successful implementation of heparin allowed for a reduction of platelet adhesion that combined with a non-haemolytic behaviour demonstrate the suitability for vascular system application.
Thus, this bio-hybrid multi-layered graft represents a novel off-the-shelf solution to overcome current limitations of TEVG.
CONCLUSIONS
We successfully tuned tubular scaffold architecture, demonstrating high control and versatility. The proposed mimetic bio-hybrid scaffold was identified as the ideal candidate to recapitulate mechanical properties, anatomical fibre orientation and ECM deposition of native vessel. Moreover, implementation of heparin demonstrates it suitability in an environment in contact with blood.
References
[1] H.H.G.Song et al. CellStem 22, 2018. [2] A.Hasan et al. Acta Biomater.10, 2014. [3] M.J.McClure et al. J.Drug Deliv.Sci.Technol. 21, 2011.
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