Development of an on-demand foaming printhead for biofabrication of constructs with heterogeneous porosity

Cell scaffolding and metabolic exchange are critical in tissue engineering and drug delivery applications, where porosity plays a crucial role in facilitating nutrient diffusion and waste removal. To tackle the challenge of biofabricating heterogeneous constructs, this study focuses on developing 3D bioprinted tunable macroporous scaffolds with a range of pore sizes. The approach utilizes the rapid cross-linking of sodium alginate via calcium chloride mist and the on-demand foaming capability of albumin within a printhead. The pore diameter is controlled by adjusting the foaming speed during printing, enabling the biofabrication of heterogeneous structures. The study examines the effects of various foaming speeds (1500, 2500, and 3500 rpm) on printability, water content, degradation, drug release, and biocompatibility properties of foams made from a bioink containing 2 % (w/v) sodium alginate, 2 % (w/v) albumin, 2 % (w/v) gelatin. At lower foaming speeds, larger pore sizes result in higher water content, degradation, and drug release due to larger pores facilitating higher water intake, quicker degradation, and shorter drug diffusion pathways. The proposed technique demonstrated excellent printability, layer adhesion, and shape fidelity, with a printability number over 0.90. A passive cell mixer was added to the foaming printhead, leading to cell-laden printed scaffolds. Fibroblast L929 cells exhibited over 90 % viability after 24 h according to the Live/dead assay, highlighting the biocompatibility of the system.