Chintan Aundhia
1* 
, Jagruti Desai
2, Swayamprakash Patel
2, Chitrali Talele
1, Bhupendra G. Prajapati
3* 1 Department of Pharmacy, Sumandeep Vidyapeeth Deemed to be University, Piparia, Vadodara, Gujarat 391760, India
2 Department of Pharmaceutical Technology, Ramanbhai Patel College of Pharmacy, Charotar University of Science and Technology (CHARUSAT), CHARUSAT Campus, Changa 388421, India
3 Department of Pharmaceutics, Parul Institute of Pharmacy, Faculty of Pharmacy and Research & Development Cell, Parul University, Waghodia, Vadodara, Gujarat 391760, India
Abstract
Smart bioinks based on hydrogel have emerged a revolutionary platform in three-dimensional bioprinting that facilitates the development of biomimetic tissue constructs with a higher level of structural and biological precision. These advanced bioinks exhibit dynamic responsiveness to physicochemical and biological stimuli, allowing precise modulation of cell matrix interactions and microenvironmental conditions. The rational design of smart bioinks has achieved considerable advances in recent years by means of controlled optimization of rheological properties, crosslinking processes, and incorporation of bioactive agents. This review gives an in-depth account of hydrogel-based smart bioinks, their design principles, physicochemical and biological properties, and printability aspects. Their use in brain tissue engineering and tumor microenvironment modelling is of special interest as their capability to replicate complex cellular structures, biochemical gradients and dynamic signalling plays a critical role. Additionally, latest trends such as recent developments in nanocomposite bioinks, co-culture, and AI-assisted bio fabrication are also discussed. Although significant advances have been made, vascularization issues, long-term functionality, and scalability issues continue to pose major barriers to clinical translation. Altogether, hydrogel-based smart bioinks may be viewed as a promising approach to the development of tissue engineering, disease modelling, and precision medicine applications.