Regeneration of skeletal system with genipin crosslinked biomaterials

Natural biomaterials, such as collagen, gelatin, and chitosan, are considered as promising candidates for use in tissue regeneration treatment, given their similarity to natural tissues regarding components and structure. Nevertheless, only receiving a crosslinking process can these biomaterials exhibit sufficient strength to bear high tensile loads for use in skeletal system regeneration. Recently, genipin, a natural chemical compound extracted from gardenia fruits, has shown great potential as a reliable crosslinking reagent, which can reconcile the crosslinking effect and biosafety profile simultaneously. In this review, we briefly summarize the genipin extraction process, biosafety, and crosslinking mechanism. Subsequently, the applications of genipin regarding aiding skeletal system regeneration are discussed in detail, including the advances and technological strategies for reconstructing cartilage, bone, intervertebral disc, tendon, and skeletal muscle tissues. Finally, based on the specific pharmacological functions of genipin, its potential applications, such as its use in bioprinting and serving as an antioxidant and anti-tumor agent, and the challenges of genipin in the clinical applications in skeletal system regeneration are also presented.