Epimedium: A Versatile Player in Bone Tissue Engineering

Epimedium is a traditional herb that has been investigated for its potential osteogenic and bone-regenerative effects, yet systematic analyses of its multi-component, multi-target mechanisms in bone metabolism and tissue engineering applications are limited. To address this knowledge gap, this narrative review systematically summarizes more than 20 bioactive constituents extracted from various parts of major medicinal Epimedium species. We elaborate on their pivotal roles in modulating osteogenic differentiation, suppressing osteoclastogenesis and bone resorption, regulating inflammatory responses, exerting antioxidant effects, promoting angiogenesis, demonstrating antitumor activity, exerting chondroprotective effects, and exhibiting antibacterial activity during bone defect repair. Furthermore, we highlight recent advancements and current trends in applying these bioactive constituents within the field of bone tissue engineering. Additionally, we compared the osteogenic and osteoprotective potentials of three metabolically related flavonoids (icariin, icaritin, and icariside II). Network pharmacology was utilized to elucidate their multi-target mechanisms in modulating bone metabolism, providing insights for future mechanistic studies. Despite the long-standing clinical use and extensive scientific investigation of Epimedium, this review identifies several challenges associated with its application in bone tissue engineering and offers constructive recommendations to overcome these limitations.