Highly-defined bioprinting of long-term vascularized scaffolds with Bio-Trap: Complex geometry functionalization and process parameters with computer aided tissue engineering

Abstract

Three-dimensional bioprinting, thanks to its great versatility, flexibility, perfect reproducibility and high speed, has recently emerged as a promising technology, especially in biological applications, making possible its use in different fields. In fact, synthetic organ manufacturing using natural derived polymers, with mechanical micro-extrusion technology, demonstrated its potential applications in tissue regeneration and vascular reconstruction but processes need to better control high resolution, degradation time and contamination. Here we propose a low cost liquid frozen deposition manufacturing 3D bioprinter with a smart and middle-ware technology, using customized algorithms, in order to support processes for tissue-engineering. We described 46 geometrical parameters in a ultra-defined architecture scaffolds that conserved original characteristics for more than 23 months after rehydration, and evaluated the mechanical characteristics, the surface micro-morphology and the related cell viability. Moreover, we demonstrated that the cells can be entrapped into Bio-Trap in the rehydrated scaffold thickness and can be maintained alive for 3 weeks. With these smart-technologies, it is possible to obtain a first evaluation of different process parameters and scaffold architecture for the fabrication of long-term organoid controlling the full cycle of scaffold fabrication from the biomaterial selection to the final 3D bio-architecture. Statement of significance – MaterialiaThis study has the aim to standardize the comparison and the analysis of the different scaffold's functionalized structure. In fact, the high number of possible functionalizations of dedicated biological structure, needs a structured data scheduling. Thus, this study shows a new method for the implementation of Computer Aided Tissue Engineering (CATE) using 3D bio-printing and smart technology with the aim to develop vertical channels, for the vascularization of the scaffold, and Bio-Traps able to entrap the cells within scaffold's height. This innovative technique, thanks to its flexibility, can support the personalization of high-defined scaffold geometries for in vitro research activities.