Biomimetic Cell Membrane-Based Drug Delivery Systems for Oral Diseases: Engineering Strategies, Targeting Mechanisms, and Translational Challenges.

Oral diseases, encompassing conditions such as periodontitis, head and neck squamous cell carcinoma, pulpitis, and mucosal infections, remain a major global health burden due to their high prevalence and complex, multifactorial pathophysiology. The unique anatomical structure of the oral cavity, together with persistent microbial challenges and dynamic immune responses, imposes substantial limitations on conventional drug delivery strategies. Biomimetic cell membrane-based materials have recently emerged as a promising class of delivery platforms, leveraging natural biological interfaces to confer inherent biocompatibility, immune evasion, prolonged circulation, specific targeting, and biofilm-interactive capabilities. These features position them as a transformative approach for improving therapeutic precision and efficacy in oral disease management. In this review, we provide a systematic and materials-oriented overview of biomimetic cell membrane-based drug delivery systems. Specifically, we discuss: (1) the biological sources, classification, and physicochemical properties of membrane-coated systems, along with their fabrication and engineering strategies; (2) the mechanistic basis of targeting, immune modulation, and nanobiointerface interactions, and their applications across representative oral diseases; and (3) current challenges, including scalable manufacturing, functional controllability, biosafety, and clinical translation. Furthermore, we highlight emerging directions such as stimuli-responsive membrane systems and multifunctional integrated platforms, aiming to provide a conceptual framework for the rational design and clinical advancement of biomimetic drug delivery systems in complex disease settings.