Melt electrowritten scaffold architectures to mimic vasculature mechanics and control neo-tissue orientation

Cardiovascular disease is one of the leading causes of death worldwide, commonly associated with the development of an arteriosclerotic plaque and impairment of blood flow in arteries. Current adopted grafts to bypass the stenosed vessel fail to recapitulate the unique mechanical behaviour of native vessels, particularly in the case of small diameter vessels (<6 mm), leading to graft failure. Therefore, in this study, melt-electrowriting (MEW) was adopted to produce a range of fibrous grafts to mimic the extracellular matrix (ECM) architecture of the tunica media of vessels, in an attempt to match the mechanical and biological behaviour of the native tissue. Initially, the range of collagen architectures within the native vessel was determined, and subsequently replicated using MEW (winding angles (WA) 45{degrees}, 26.5{degrees}, 18.4{degrees}, 11.3{degrees}). These scaffolds recapitulated the anisotropic, non-linear mechanical behaviour of native carotid blood vessels. Moreover, these grafts facilitated human mesenchymal stromal/stem cell (hMSC) infiltration, differentiation, and ECM deposition that was independent of WA. The bioinspired MEW fibre architecture promoted cell alignment and preferential neo-tissue orientation in a manner similar to that seen in native tissue, particularly for WA 18.4{degrees} and 11.3{degrees}, which is a mandatory requirement for long-term survival of the regenerated tissue post-scaffold degradation. Lastly, the WA 18.4{degrees} was translated to a tubular graft and was shown to mirror the mechanical behaviour of small diameter vessels within physiological strain. Taken together, this study demonstrates the capacity to use MEW to fabricate bioinspired grafts to mimic the tunica media of vessels and recapitulate vascular mechanics which could act as a framework for small diameter graft development and functional long-term tissue regeneration.