A lymphatic organ-on-a-chip reveals flow-responsive LEC paracrine signals promoting BMSC osteogenesis in jawbone regeneration

validation using a murine molar extraction model with controlled occlusal loading revealed that occlusal loading promoted lymphangiogenesis and accelerated alveolar bone regeneration, accompanied by elevated WISP1 expression within alveolar sockets. Conversely, pharmacological suppression of lymphatic expansion through MAZ51 administration impaired bone formation while reducing WISP1 levels, thereby confirming the functional contribution of lymphatic vessels in alveolar bone regeneration. Together, these findings demonstrate that LECs function as mechanoresponsive regulators that transduce shear-related cues into osteoinductive signals through WISP1-mediated paracrine communication. Our study uncovers a previously unrecognized lymphatic-osteogenic signaling axis and establishes a physiologically relevant OoC platform for systematic investigation of lymphatic mechanotransduction in bone regeneration.