An injectable liposome-anchored teriparatide incorporated gallic acid-grafted gelatin hydrogel for osteoarthritis treatment

• Published in: Nature communications Vol. 14; no. 1; pp. 3159 - 18
• Main Authors: Li, Guoqing, Liu, Su, Chen, Yixiao, Zhao, Jin, Xu, Huihui, Weng, Jian, Yu, Fei, Xiong, Ao, Udduttula, Anjaneyulu, Wang, Deli, Liu, Peng, Chen, Yingqi, Zeng, Hui
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 31.05.2023; Nature Publishing Group; Nature Portfolio
• Subjects: 1-Phosphatidylinositol 3-kinase; 13/1; 13/107; 13/31; 13/51; 140/131; 147/135; 38/39; 631/45/776/813; 631/61/54/990; 639/166/985; 639/301/54/152; 64/60; 692/308/575; 82/80; AKT protein; Animals; Arthritis; Biomaterials; Biomedical materials; Cartilage diseases; Cell proliferation; Controlled release; Gallic acid; Gelatin; Glycosaminoglycans; Humanities and Social Sciences; Hydrogels; Hydrogels - therapeutic use; Injection; Injections, Intra-Articular; Liposomes; Liposomes - therapeutic use; Mice; multidisciplinary; Osteoarthritis; Osteoarthritis - drug therapy; Parathyroid hormone; Phosphatidylinositol 3-Kinases; Science; Science (multidisciplinary); Signal transduction; Sustained release; Teriparatide - therapeutic use
• ISSN: 2041-1723; 2041-1723
• 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. Osteoarthritis is a common disease that causes pain and difficulty moving joints. Here the authors present an injectable gelatin-based hydrogel that slowly releases teriparatide drug to avoid frequent injections, offering a potential solution for patients with osteoarthritis.