Blood-Vessel Mimicking Structures by Stereolithographic Fabrication of Small Porous Tubes Using Cytocompatible Polyacrylate Elastomers, Biofunctionalization and Endothelialization

Abstract

Blood vessel reconstruction is still an elusive goal for the development of in vitro models as well as artificial vascular grafts. In this study, we used a novel photo-curable cytocompatible polyacrylate material (PA) for freeform generation of synthetic vessels. We applied stereolithography for the fabrication of arbitrary 3D tubular structures with total dimensions in the centimeter range, 300 µm wall thickness, inner diameters of 1 to 2 mm and defined pores with a constant diameter of approximately 100 µm or 200 µm. We established a rinsing protocol to remove remaining cytotoxic substances from the photo-cured PA and applied thio-modified heparin and RGDC-peptides to functionalize the PA surface for enhanced endothelial cell adhesion. A rotating seeding procedure was introduced to ensure homogenous endothelial monolayer formation at the inner luminal tube wall. We showed that endothelial cells stayed viable and adherent and aligned along the medium flow under fluid-flow conditions comparable to native capillaries. The combined technology approach comprising of freeform additive manufacturing (AM), biomimetic design, cytocompatible materials which are applicable to AM, and biofunctionalization of AM constructs has been introduced as BioRap® technology by the authors.

Leachable Poly(Trimethylene Carbonate)/CaCO3 Composites for Additive Manufacturing of Microporous Vascular Structures

“…Moreover, the smallest particle sizes ranged from 75 to 180 μm, resulting in large pores [ 40 ]. Printing of branched porous vascular structures by SLA using a cytocompatible polyacrylate has been reported, but the designed pores had a diameter of 100 μm which could not be covered by endothelial cells [ 41 ]. This problem will not be encountered with the microporous vascular structures presented in the present paper.…”

Bioprinting for vascular and vascularized tissue biofabrication

“…These techniques offer sparse control over pore size and shape while also lacking in precision requirement of target architectures. To overcome these limitations, rapid prototyping techniques have been introduced such as vat photopolymerization [62,63], material extrusion [64,65], and sheet lamination [66].…”

Vascularized Microfluidics and the Blood–Endothelium Interface

“…The currently available fabrication methods utilized in the development of vascularized microfluidic models, however, have limitations with regards to both channel size, particularly at the smallest diameters, and geometry. Perfusable channel sizes range from tens of micrometers in the case of photolithography-based models using PDMS as a substrate [46] and "bottom-up" approaches [58] to on the order of 200-400 µm in the case of inkjet [176] and 3D printing fabrication methods [177]. The ability to create microchannels at both ends of the size spectrum come with limitations, however.…”