Novel Protein‐Rich Bioactive Bioink Stimulates Cellular Proliferation and Response in 3D Bioprinted Volumetric Constructs

This work describes a protein-rich, low-cost, bioactive bioink, prepared by adding eggwhite powder to functionalize an established alginate-methylcellulose hydrogel blend and enhance its cellular response. The bioink not only maintains favorable printability and high shape fidelity but also exhibits remarkable bioactivity, thereby improving the viability of encapsulated cells within the bioprinted constructs.

Abstract

3D extrusion bioprinting, a promising and widely adopted technology in the emerging field of biofabrication, has gained considerable attention for its ability to fabricate hierarchically structured, native-mimicking tissue substitutes with precisely defined cell distributions. Despite notable advancements, the limited availability of suitably bioactive bioinks remains a major challenge, hindering the construction of volumetric tissue substitutes effectively mimicking biological functionality. Therefore, this work proposes a protein-rich, low-cost, bioactive bioink: abundantly available eggwhite powder (EWP) is leveraged to functionalize an alginate-methylcellulose (AlgMC) hydrogel matrix and enhance cellular response. The developed EWP-supplemented bioinks not only maintain favorable printability and high shape fidelity but also exhibit remarkable bioactivity. Notably, incorporating EWP into AlgMC-based bioinks enhances shear-thinning features, thereby improving the viability of encapsulated cells within the bioprinted constructs. The versatility and biofunctionality of EWP in bioprinted constructs are demonstrated using three distinct cell types, encompassing sources such as a stem cell line, human soft skin, and stiff bone tissues. Furthermore, the promising and wide applicability of the EWP-supplemented bioink for biofabrication is demonstrated exemplarily in core-shell and multi-channel bioprinting strategies as a proof-of-concept for functional tissue construction. These findings underscore the significant and versatile potential of this novel bioink in biofabrication and biomedical applications.