3D printed grafts with gradient structures for organized vascular regeneration

Abstract

Synthetic vascular grafts suitable for small-diameter arteries (< 6 mm) are in great need. However, there are still no commercially available small-diameter vascular grafts (SDVGs) in clinical practice due to thrombosis and stenosis after in vivo implantation. When designing SDVGs, many studies emphasized reendothelization but ignored the importance of reconstruction of the smooth muscle layer (SML). To facilitate rapid SML regeneration, a high-resolution 3D printing method was used to create a novel bilayer SDVG with structures and mechanical properties mimicking natural arteries. Bioinspired by the collagen alignment of SML, the inner layer of the grafts had larger pore sizes and high porosity to accelerate the infiltration of cells and their circumferential alignment, which could facilitate SML reconstruction for compliance restoration and spontaneous endothelialization. The outer layer was designed to induce fibroblast recruitment by low porosity and minor pore size and provide SDVG with sufficient mechanical strength. One month after implantation, the arteries regenerated by 3D-printed grafts exhibited better pulsatility than electrospun grafts, with a compliance (8.9%) approaching that of natural arteries (11.36%) and significantly higher than that of electrospun ones (1.9%). The 3D-printed vascular demonstrated a three-layer structure more closely resembling natural arteries while electrospun grafts showed incomplete endothelium and immature SML. Our study shows the importance of SML reconstruction during vascular graft regeneration and provides an effective strategy to reconstruct blood vessels through 3D-printed structures rapidly.

Small diameter vascular grafts: progress on electrospinning matrix/stem cell blending approach

“…Its advantages are simple preparation and flexible design of adhesive cells and molecules in each layer, but the junction between layers may be not tight and prone to cracks, affecting the performance of the scaffold ( Wang et al, 2016 ). 3D printing (also known as additive manufacturing) is a new technology that displays the 3D shape through tomography and computer simulation, and then reconstructs the shape by bioink materials ( Chen et al, 2024 ). However, the harsh conditions of SDVGs make the material requirements of 3D printing for this application very high, and the high costs for biological 3D printing equipments to control the micro/nano structure limit the application of this technology in SDVGs as well.…”