Mechanobiological engineering strategies for oral and maxillofacial tissue regeneration

Mechanical forces are central determinants of development, homeostasis, and pathology in oral and maxillofacial tissues, yet most regenerative strategies continue to prioritize biochemical signaling over mechanical control. In anatomically and functionally heterogenous tissues such as dentin-pulp, periodontium, temporomandibular joint, oral mucosa, and salivary glands, mechanics is not a secondary cue but a primary regulator of cell fate, immune responses, and tissue integration. This review reframes oral and maxillofacial regeneration through a mechanobiological engineering lens, summarizing how region-specific mechanical loading is sensed and transduced through focal adhesions, mechanosensitive ion channels, cytoskeletal tension, and nuclear mechanotransduction to coordinate tissue-specific repair programs. We organize recent advances into two complementary strategies. Intrinsic mechanobiological design exploits biomaterial stiffness, hierarchical topography, anisotropic and modular architectures, and piezoelectric functionality to recreate tissue-appropriate mechanical niches. Extrinsic mechanotherapy leverages engineered in vitro platforms and clinically adaptable physical modalities including vibration, low-intensity ultrasound, electrical stimulation, and magnetic fields – to activate endogenous regenerative pathways. We further discuss critical barriers to clinical translation, including the lack of physiologically realistic testbeds, insufficient standardization of mechanical dose, fatigue and durability under cyclic loading, and challenges in scalable manufacturing. Finally, we highlight emerging opportunities in adaptive biomaterials coupled with multiscale modeling and AI-assisted, data-driven design to integrate mechanical, biological, and functional outcome data. By positioning mechanics as a design and dosing variable rather than a passive property, this review provides a framework for developing reproducible, clinically relevant therapies that restore both biological function and mechanical performance in oral and maxillofacial tissues. • Mechanobiology-informed biomaterials address oral and maxillofacial complexity • Intrinsic cues: stiffness, anisotropic topographies, and piezoelectric materials • Extrinsic cues: vibration, ultrasound, electrical, and magnetic stimulation platforms • Integrative strategies guide functional and mechanically competent regeneration