Biomimetic 3D bioprinting of cellular laden nanocomposite scaffold through co-axial and core-co-cultured structure

Fahimeh Shahabipour

Abstract

There is a need to recapitulate the native complexity of bone structure within engineered 3D structures with tailored bi­ological and mechanical properties. In this study, we sug­gest an innovative cell-printing process, supplemented with core/shell nozzle and co-cultured/mono-cultured methods, to achieve 3D osteon-like structures through cell-laden bio­inks using an extrusion-based 3D bioprinter in one-step. In this study, vascularization promoting and osteogenic bioinks were developed based on different concentration of Gel­MA-alginate hydrogels with the incorporation of hydroxy­apatite nanoparticles. These hydrogels were chosen due to their suitable mechanical stability, swelling ratio, and print­ability. To obtain a core/shell osteon-like structure (CSBP), we used a vascularization bioink combined HUVECs in the core region, and used osteogenic- MC3T3-E1 cells-laden bioinks in the shell region. Pure gelatin was concentration in all bioinks to support both of core and shell structures during 3D bioprinting. Core-co-cultured osteon-like struc­ture (CCBP) was fabricated through co-culturing of HU­VECs and MC3T3 cells within bioink in the core region. Mono-cultured printed structure composed of single cell lines served as a control. The fabricated 3D-core-cocultured of HUVECs-MC3T3 cells showed significantly higher cell viability (84%) compared to that (78%) of a 3D-core/shell of HUVECs/MC3T3 cells. Both fabricated structures exhib­ited outstanding cell viability in comparison with (65%) of mono-cultured 3D cell-laden scaffold (control). In addition, significant increases in osteogenic properties were observed in the co-culture samples versus the mono-culture controls. We demonstrated that both co-culture configurations were able to promote mineral deposition in the absence of exog­enous osteogenic factors. Although the CSBP configuration displayed less viability than CCBP, this structure still exhib­ited good osteogenic and angiogenic properties. In conclu­sion, this investigation provided highlighted the potential of both structures as biomimetic bone scaffolds for complex bone tissue and other tissue engineering application.