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Conventional therapies often face significant obstacles when treating inflammatory conditions, underscoring the need to deliver therapeutic agents in a targeted and controlled manner. Biomaterials that respond to specific environmental stimuli, such as temperature, pH, light, electrical signals, magnetic fields, and mechanical forces, provide innovative solutions by enabling controlled drug delivery. These stimuli-responsive biomaterials provide the ability to trigger responses tailored to specific biomedical needs. Hence, to appreciate the full spectrum of responsive materials and their potential applications, it is essential to generate a comprehensive classification based on the factors that trigger them. This chapter provides a holistic discussion on how different biomaterials transform in response to external cues, elucidating their mechanisms of action and potential applications in treating inflammatory disorders. First, challenges faced by current treatment options are highlighted, followed by the role of advanced biomaterials in combating these challenges. Next, a thorough classification of environmental stimuli and their respective biomaterials is provided. Design principles and mechanisms have also been explored using case studies. Furthermore, an overview of clinical progress and translational research is presented. The chapter wraps up with a discussion on future directions and obstacles, including biocompatibility, scalability, and cost-efficiency, all crucial for the widespread acceptance of these technologies.