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.

天然生物材料，如胶原蛋白、明胶和壳聚糖，由于其成分和结构与天然组织相似，被认为是用于组织再生治疗的有前途的候选材料。然而，只有经过交联过程，这些生物材料才能表现出足够的强度来承受高拉伸载荷，用于骨骼系统再生。最近，从栀子果实中提取的天然化合物京尼平作为可靠的交联剂显示出了巨大的潜力，它可以同时协调交联效果和生物安全性。在这篇综述中，我们简要总结了京尼平的提取工艺、生物安全性和交联机制。随后详细讨论了京尼平在辅助骨骼系统再生方面的应用，包括重建软骨、骨、椎间盘、肌腱和骨骼肌组织的进展和技术策略。最后，基于京尼平的具体药理功能，介绍了其潜在应用，如在生物打印中的应用、作为抗氧化剂和抗肿瘤剂，以及京尼平在骨骼系统再生临床应用中面临的挑战。