Department of Bone & Joint Surgery, Peking University Shenzhen Hospital, Shenzhen, 518036, PR China.
National & Local Joint Engineering Research Center of Orthopaedic Biomaterials, Peking University Shenzhen Hospital, Shenzhen, 518036, PR China.
Nat Commun. 2023 May 31;14(1):3159. doi: 10.1038/s41467-023-38597-0.
Intra-articular injection of therapeutics is an effective strategy for treating osteoarthritis (OA), but it is hindered by rapid drug diffusion, thereby necessitating high-frequency injections. Hence, the development of a biofunctional hydrogel for improved delivery is required. In this study, we introduce a liposome-anchored teriparatide (PTH (1-34)) incorporated into a gallic acid-grafted gelatin injectable hydrogel (GLP hydrogel). We show that the GLP hydrogel can form in situ and without affecting knee motion after intra-articular injection in mice. We demonstrate controlled, sustained release of PTH (1-34) from the GLP hydrogel. We find that the GLP hydrogel promotes ATDC5 cell proliferation and protects the IL-1β-induced ATDC5 cells from further OA progression by regulating the PI3K/AKT signaling pathway. Further, we show that intra-articular injection of hydrogels into an OA-induced mouse model promotes glycosaminoglycans synthesis and protects the cartilage from degradation, supporting the potential of this biomaterial for OA treatment.
关节内注射疗法是治疗骨关节炎(OA)的有效策略,但由于药物扩散迅速,需要高频注射,因此需要开发一种用于改善药物输送的生物功能水凝胶。在本研究中,我们引入了一种脂质体锚定的甲状旁腺素(PTH(1-34)),并将其纳入到一种没食子酸接枝明胶可注射水凝胶(GLP 水凝胶)中。我们表明,GLP 水凝胶可以在原位形成,并且在小鼠关节内注射后不会影响膝关节运动。我们证明了 PTH(1-34)可以从 GLP 水凝胶中得到控制、持续释放。我们发现,GLP 水凝胶通过调节 PI3K/AKT 信号通路促进 ATDC5 细胞增殖,并保护 IL-1β诱导的 ATDC5 细胞免受进一步的 OA 进展。此外,我们表明,向 OA 诱导的小鼠模型关节内注射水凝胶可促进糖胺聚糖的合成,并保护软骨免受降解,这支持了这种生物材料治疗 OA 的潜力。