Electrospinning of biomimetic scaffolds for tissue-engineered vascular grafts: threading the path

Abstract

Tissue-engineered vascular grafts (TEVGs) offer an alternative to synthetic grafts for the surgical treatment of atherosclerosis and congenital heart defects, and may improve graft patency and patient outcomes after implantation. Electrospinning is a versatile manufacturing process for the production of fibrous scaffolds. This review aims to investigate novel approaches undertaken to improve the design of electrospun scaffolds for TEVG development. The review describes how electrospinning can be adapted to produce aligned nanofibrous scaffolds used in vascular tissue engineering, while novel processes for improved performance of such scaffolds are examined and compared to evaluate their effectiveness and potential. By highlighting new drug delivery techniques and porogenic technologies, in addition to analyzing in vitro and in vivo testing of electrospun TEVGs, it is hoped that this review will provide guidance on how the next generation of electrospun vascular graft scaffolds will be designed and tested for the potential improvement of cardiovascular therapies.

Keywords::

• atherosclerosis
• congenital heart defect
• electrospinning
• nanotechnology
• tissue engineering
• vascular graft

Financial & competing interests disclosure

This work was supported by the National Children’s Research Centre (Our Lady’s Children’s Hospital, Crumlin, Dublin)/Children's Medical and Research Foundation (grant no. H/12/1). The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

No writing assistance was utilized in the production of this manuscript.

Key issues

• The hierarchical structure of the native artery permits complex interactions between its components and surroundings that are difficult to mimic using synthetic materials. The failure of small diameter synthetic grafts occurs through intimal hyperplasia and thrombogenesis due to either compliance mismatch or inadequate endothelialization.

• Electrospinning is a simple, flexible and efficient method of producing tubular scaffolds for the development of biomimetic tissue-engineered vascular grafts (TEVGs) from a wide range of natural and synthetic polymeric materials.

• The aligned nanofibrous environment provided by electrospun scaffolds closely resembles the native extracellular matrix and induces cellular orientation and the alignment of synthesized extracellular matrix proteins. This leads to an improvement in the strength and elasticity of the TEVG.

• Cellular infiltration can be a significant hampering issue with electrospinning due to the narrow pore morphology of electrospun scaffolds; however, a number of approaches have been developed in recent years to improve cellular infiltration such as porogenic technologies, mixed-morphology (micro- to nano-scale) scaffolds and electrospraying of cells.

• Bioactivation of scaffolds represents an opportunity to increase the quality of engineered tissues and consequently improve the mechanical properties of vascular grafts.

• In vitro mechanical testing has demonstrated how the mechanical properties of electrospun grafts can be tuned to mimic those of the native artery, which indicates excellent potential for the in situ recruitment of cell populations and tissue generation.

• While few studies have been published, the performance of electrospun TEVGs in vivo demonstrates the feasibility and significant potential of the electrospinning approach for the manufacture of TEVGs.

Notes

Data taken from [4].