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Smart Injectable Hydrogels: From In-Situ Gelation to On-Demand Drug Release in Regenerative Medicine

Authors :

Leyla Mirzaei¹ Adnan Alizadeh Naeini² Neda Sadat Miragha Babaei³

1- دانشکده مهندسی مواد دانشگاه صنعتی شیراز 2- دانشکده مهندسی مواد دانشگاه شیراز 3- دانشکده مهندسی پزشکی، واحد علوم و تحقیقات، دانشگاه آزاد اسلامی

Keywords :

Injectable hydrogels،smart materials،in-situ gelation،controlled drug release،regenerative medicine،tissue engineering

Abstract :

Injectable hydrogels have emerged as a transformative class of biomaterials, poised to revolutionize regenerative medicine and targeted drug delivery. Their ability to be administered via minimally invasive procedures and form solid scaffolds in situ addresses many limitations of conventional therapies and pre-formed implants. This review focuses on the evolution of these platforms into "smart" systems, which are engineered to respond to specific physiological or external stimuli. We provide a comprehensive overview of the fundamental polymeric components, contrasting the biocompatibility of natural polymers with the tunability of synthetic analogues, and highlighting the rise of hybrid systems. A central focus is placed on the diverse mechanisms of in situ gelation, from reversible physical crosslinking to stable covalent bond formation, which dictate the material's mechanical properties, injectability, and degradation profile. Furthermore, this review systematically details the engineering of stimuli-responsive behaviors—including sensitivity to temperature, pH, light, redox potential, and enzymes—that enable on-demand therapeutic release. We explore how these smart functionalities are being leveraged in cutting-edge applications, including advanced wound healing, cardiac and neural tissue engineering, osteochondral repair, and localized chemotherapy. Finally, we address the persistent challenges facing clinical translation and discuss future perspectives, including the development of multi-responsive systems, 4D bioprinting, and immunomodulatory materials that promise to usher in a new era of personalized and controlled regenerative therapies.