Pharmacological evaluation and advantage characterization of a novel Eucommia ulmoides Hydrogel in promoting fracture healing

Delayed fracture healing and nonunion continue to pose substantial challenges in orthopedic clinical practice. Existing medications for fracture treatment can, to a certain degree, promote fracture healing. However, they are plagued by problems such as unstable efficacy, slow onset, and frequent adverse effects. In this study, leveraging BanGel patented technology, we developed a novel Eucommia ulmoides-based hydrogel. This was achieved by integrating Eucommia ulmoides, a traditional Chinese medicine renowned for its liver and kidney tonifying and bone-strengthening properties, with a hydrogel delivery system. A transverse mid-shaft tibial fracture rat model was established. Behavioral assessments, serological analysis, radiological and histopathological examinations were employed to observe the dynamic changes during the fracture and subsequent healing processes. The efficacy of the Eucommia ulmoides hydrogel in promoting fracture healing was objectively evaluated. Moreover, the therapeutic advantages of the hydrogel were compared with those of oral and direct topical administrations containing the same dosage of Eucommia ulmoides. All animal experiments were approved by the Laboratory Animal Welfare Ethics Committee of the Laboratory Animal Center of the Institute of Basic Theory of Chinese Medicine, China Academy of Traditional Chinese Medicine, and were conducted in accordance with the relevant guidelines and regulations (approval No. IBTCMCACMS21-2406-03). The results showed that Eucommia hydrogel can significantly alleviate the early symptoms of fractured, promote callus formation, improve trabecular parameters and cortical bone continuity, and regulate the dynamic balance of bone formation and absorption. Compared with oral and topical applications of the same dose of Eucommia ulmoides, the Eucommia ulmoides hydrogel exhibited a faster onset and stronger permeability. Further mechanism exploration and verification results showed that Eucommia ulmoides can promote fracture healing by activating the serine/threonine protein kinase 1/β-catenin (AKT1/β-catenin) signaling axis to regulate the expression of Runt-related transcription factor 2 (RUNX2) and receptor activator of nuclear factor κB ligand/osteoprotegerin (RANKL/OPG). In summary, the novel Eucommia ulmoides hydrogel shows distinct advantages in promoting fracture healing and has potential clinical application value.