Bhuyan Samapika, Swain Subhasmita, Misra R D K, Rautray Tapash R
Biomaterials and Tissue Regeneration Laboratory, Centre of Excellence, Siksha 'O' Anusandhan (Deemed to be University), Bhubaneswar, Odisha, India.
Metallurgical, Materials and Biomedical Engineering Department, The University of Texas at El Paso, El Paso, Texas, 79968, USA.
Int J Nanomedicine. 2025 Jun 13;20:7443-7468. doi: 10.2147/IJN.S525580. eCollection 2025.
Articular cartilage degradation and osteocartilage defects are the most prevalent concerns that vary from localized to more systemic forms of cartilage disease. However, regulating chondrogenic differentiation within the joints remains a significant challenge. Kartogenin, a small heterocyclic compound, has recently garnered considerable attention as a potential therapeutic agent, owing to both chondrogenic and chondroprotective properties for intra-articular therapy. Initially, it was created for osteoarthritis; it has also been used to address various diseased conditions, such as the regeneration of disc and bone-tendon junctions. On top of that, it preserves the equilibrium between cartilage catabolism and anabolism, while also mitigating inflammation and alleviating pain by preventing damage induced by cytokines. To modulate tissue function and cellular behaviour, it is crucial to have sustained release of ketogenic through an appropriate delivery system. A multitude of biomaterial-based carriers have been developed for the prolonged release of kartogenin. Moreover, many biological mechanisms of action of kartogenin have been identified. The most critical molecular mechanism among them is the dissociation of filamin A from core-binding factor (CBF)-β induced by kartogenin. Filamin A subsequently translocates to the nucleus, where it engages with RUNX-1 to transcribe genes implicated in the chondrogenesis of mesenchymal stem cells. This review focuses on the development of biomaterials functionalized with kartogenin, including their structure, design, physicochemical properties, biological roles, molecular mechanisms of action, and applications in tissue engineering and regenerative medicine. In conclusion, we discussed the future possibilities and challenges posed by recent advancements in kartogenin research and their potential applications in tissue regeneration.
关节软骨退变和骨软骨缺损是最常见的问题，其范围从局部性到更全身性的软骨疾病形式各不相同。然而，调控关节内的软骨形成分化仍然是一项重大挑战。Kartogenin是一种小分子杂环化合物，由于其具有关节内治疗的软骨形成和软骨保护特性，最近作为一种潜在的治疗剂受到了广泛关注。最初，它是为骨关节炎而研发的；它也被用于治疗各种疾病状况，如椎间盘和骨-肌腱连接处的再生。除此之外，它能维持软骨分解代谢和合成代谢之间的平衡，同时还能通过防止细胞因子诱导的损伤来减轻炎症和缓解疼痛。为了调节组织功能和细胞行为，通过合适的递送系统持续释放Kartogenin至关重要。已经开发了多种基于生物材料的载体用于Kartogenin的长效释放。此外，Kartogenin的许多生物学作用机制也已被确定。其中最关键的分子机制是Kartogenin诱导细丝蛋白A与核心结合因子（CBF）-β解离。细丝蛋白A随后转移到细胞核，在那里它与RUNX-1结合以转录与间充质干细胞软骨形成相关的基因。本综述重点关注用Kartogenin功能化的生物材料的发展，包括它们的结构、设计、物理化学性质、生物学作用、分子作用机制以及在组织工程和再生医学中的应用。总之，我们讨论了Kartogenin研究最新进展带来的未来可能性和挑战及其在组织再生中的潜在应用。
