Mechanobiology of orofacial tissues: principles, mechanisms, and therapeutic applications.

The orofacial system is constantly subjected to complex and dynamic mechanical forces and exhibits highly specialized mechanosensory and mechanoresponsive behaviors. However, current studies are mostly limited to single tissues or specific pathway analyses, which are insufficient to reveal a comprehensive mechanoregulation network. Here, we propose a three-dimensional integrative framework of mechanobiology to systematically characterize oral tissue responses across three interconnected levels: (1) mechanical microenvironment and tissue-specific responses (phenomenological level); (2) molecular regulatory networks driven by mechanical stimuli (mechanistic level); and (3) therapeutic strategies informed by mechanical cues (translational level). Guided by this framework, we delineated an evolutionary trajectory in the design of mechanoresponsive biomaterials, from passive mechanical compliance to active mechanoregulation and ultimately to intelligent, self-adaptive systems, which may offer a reframed perspective for orofacial regenerative medicine. Furthermore, this review provides a preliminary exploration of the potential link between the oral mechanical environment and systemic health, suggesting the potential to inspire future research on oral intervention strategies targeting systemic diseases. Moreover, by summarizing the current advancements, we highlight that future endeavors should focus on key challenges, such as the development of real-time monitoring technologies, the inspiration of smart responsive materials, and the establishment of clinical translation standards. Collectively, this review offers an integrative conceptual framework for understanding the mechanical regulation mechanisms in orofacial tissues and provides new insights for next-generation tissue engineering strategies.