Enhancing Endogenous Hyaluronic Acid in Osteoarthritic Joints with an Anti-Inflammatory Supramolecular Nanofiber Hydrogel Delivering HAS2 Lentivirus.

Autor: Zhou F; Department of Orthopaedic Surgery, The First Affiliated Hospital, Medical 3D Printing Center, Orthopedic Institute, School of Biology & Basic Medical Sciences, Suzhou Medical College, Soochow University, Suzhou, Jiangsu, 215000, P. R. China., Chen M; Institute of Functional Nano and Soft Materials (FUNSOM), Jiangsu Key Laboratory for Carbon-Based Functional Materials and Devices, Soochow University, Suzhou, Jiangsu, 215123, P. R. China., Qian Y; Department of Orthopaedic Surgery, The First Affiliated Hospital, Medical 3D Printing Center, Orthopedic Institute, School of Biology & Basic Medical Sciences, Suzhou Medical College, Soochow University, Suzhou, Jiangsu, 215000, P. R. China., Yuan K; Shanghai Key Laboratory of Orthopaedic Implants, Department of Orthopaedic Surgery, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200011, P. R. China., Han X; Department of Orthopaedics, Qilu Hospital of Shandong University, Shandong University Center for Orthopaedics, Advanced Medical Research Institute, Cheeloo College of Medicine, Shandong University, Jinan, Shandong, 250012, P. R. China., Wang W; Department of Orthopaedic Surgery, The First Affiliated Hospital, Shihezi University School of Medicine, Shihezi, Xinjiang, 832099, P. R. China., Guo JJ; Department of Orthopaedic Surgery, The First Affiliated Hospital, Medical 3D Printing Center, Orthopedic Institute, School of Biology & Basic Medical Sciences, Suzhou Medical College, Soochow University, Suzhou, Jiangsu, 215000, P. R. China., Chen Q; Institute of Functional Nano and Soft Materials (FUNSOM), Jiangsu Key Laboratory for Carbon-Based Functional Materials and Devices, Soochow University, Suzhou, Jiangsu, 215123, P. R. China., Li B; Department of Orthopaedic Surgery, The First Affiliated Hospital, Medical 3D Printing Center, Orthopedic Institute, School of Biology & Basic Medical Sciences, Suzhou Medical College, Soochow University, Suzhou, Jiangsu, 215000, P. R. China.
Jazyk: angličtina
Zdroj: Small (Weinheim an der Bergstrasse, Germany) [Small] 2024 Oct; Vol. 20 (40), pp. e2400542. Date of Electronic Publication: 2024 Apr 09.
DOI: 10.1002/smll.202400542
Abstrakt: Osteoarthritis (OA) management remains challenging because of its intricate pathogenesis. Intra-articular injections of drugs, such as glucocorticoids and hyaluronic acid (HA), have certain limitations, including the risk of joint infection, pain, and swelling. Hydrogel-based therapeutic strategies have attracted considerable attention because of their enormous therapeutic potential. Herein, a supramolecular nanofiber hydrogel is developed using dexamethasone sodium phosphate (DexP) as a vector to deliver lentivirus-encoding hyaluronan synthase 2 (HAS2) (HAS2@DexP-Gel). During hydrogel degradation, HAS2 lentivirus and DexP molecules are slowly released. Intra-articular injection of HAS2@DexP-Gel promotes endogenous HA production and suppresses synovial inflammation. Additionally, HAS2@DexP-Gel reduces subchondral bone resorption in the anterior cruciate ligament transection-induced OA mice, attenuates cartilage degeneration, and delays OA progression. HAS2@DexP-Gel exhibited good biocompatibility both in vitro and in vivo. The therapeutic mechanisms of the HAS2@DexP-Gel are investigated using single-cell RNA sequencing. HAS2@DexP-Gel optimizes the microenvironment of the synovial tissue by modulating the proportion of synovial cell subpopulations and regulating the interactions between synovial fibroblasts and macrophages. The innovative nanofiber hydrogel, HAS2@DexP-Gel, effectively enhances endogenous HA production while reducing synovial inflammation. This comprehensive approach holds promise for improving joint function, alleviating pain, and slowing OA progression, thereby providing significant benefits to patients.
(© 2024 Wiley‐VCH GmbH.)
Databáze: MEDLINE
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