4D bioprinting of protein-based bioinks for tissue engineering and disease models

Four-dimensional (4D) printing enables the creation of dynamic structures that can change, altering their shape, properties, or functionality in response to stimuli over time by incorporating time as a fourth dimension. This revolutionary approach has gotten significant attention across various fields, with recent advancements in integrating smart biomaterials, biological components, and living cells into dynamic, three-dimensional (3D) constructs. Among the myriad of biomaterials available, protein-based (PB) polymers have emerged as promising due to their inherent biocompatibility, biodegradability, and ability to interact with and mimic the extracellular matrix (ECM). This review provides a comprehensive overview of 4D bioprinting, involving PB bioinks, and explores key principles, mechanisms, strategies, and types. It discusses essential requirements, such as printability, biodegradation, and mechanical integrity, as well as strategies for designing stimuli-responsive 4D bioinks. Furthermore, it comprehensively explores emerging trends in applying these bioinks for the 4D bioprinting of tissue scaffolds and their utility in disease modeling. Finally, it addresses current challenges and prospects, aiming to provide readers with a thorough understanding of recent developments in this groundbreaking technology towards adaptability in regenerative medicine and disease models.