Rajeev, AshwinAshwinRajeevPatil, JugalJugalPatilYadav, Amit K.Amit K.YadavModi, UnnatiUnnatiModiSolanki, RaghuRaghuSolankiBhatia, DhirajDhirajBhatia2026-02-042026-02-042026-01-012373-987810.1021/acsbiomaterials.5c017842-s2.0-105029687471https://repository.iitgn.ac.in/handle/IITG2025/34524Mechanoresponsive biomaterials are a revolutionary class of materials designed to respond dynamically to mechanical stimuli, providing tissue engineering and regenerative medicine with precise control over biological processes. Through processes including supramolecular interactions, strain stiffening, and force-induced conformational changes, these materials, which include hydrogels, elastomers, and piezoelectric composites, imitate the mechanics exclusive to biological tissues. Additionally, mechanoresponsive systems improve drug delivery by releasing drugs in response to pH changes or mechanical strain using various materials, including magnetic scaffolds and ultrasound-triggered micelles. Despite advancements in numerous arenas of biological sciences, problems with clinical translation, scalability, and long-term biocompatibility still exist. New developments combine technologies like 4D bioprinting to create dynamic, patient-specific scaffolds and artificial intelligence (AI)-assisted design to maximize material qualities. To achieve material innovation with the desired level of biological complexity, future initiatives should focus on multifunctional platforms that combine mechanical, electrical, and biochemical inputs at an advanced level. This review dives into several aspects of mechanoresponsive biomaterials by navigating through the fabrication methods, underlying principles, inception of these in biomedical applications, and progression through the current research settings.en-USArticleWOS:001672117800001