Long-term delivery of salvianolic acid B via injectable chitosan thermosensitive hydrogel for the treatment of steroid-induced osteoporosis

Steroid-induced osteoporosis presents a significant clinical challenge, requiring innovative therapeutic strategies to improve treatment outcomes. Salvianolic acid B (SalB), a potent small-molecule drug known for its ability to enhance microcirculation and promote osteogenic differentiation, is hindered by poor oral bioavailability. This study developed an injectable, minimally invasive thermosensitive hydrogel system for the sustained release of SalB into local tissues. A chitosan/β-glycerophosphate (CS/β-GP) hydrogel, known for its temperature-sensitive, thermally reversible gelation properties, was utilized as the base material. Sodium alginate (SA) was incorporated to enhance mechanical strength and accelerate gelation time, forming the CS/β-GP-SA hydrogel as a drug delivery vehicle . SalB was loaded at varying concentrations, and characterization was performed using FTIR spectrometry, alkaline phosphatase staining, alizarin red staining, and real-time quantitative polymerase chain reaction (qRT-PCR). The hydrogel's impact on rat bone marrow mesenchymal stem cells (RBMSCs) was assessed, and therapeutic efficacy was tested in a steroid-induced osteoporosis model using micro-CT, enzyme-linked immunosorbent assay (ELISA), and histological analysis. Characterization and in vitro experiments revealed increased number of pore size, reduced porosity, and enhanced mechanical strength in drug-loaded hydrogels. In vitro release studies confirmed a steady and sustained release of SalB over time. The CS/β-GP-SA hydrogel exhibited biocompatibility , with high-dose SalB-loaded hydrogels significantly promoting RBMSCs proliferation and osteogenic differentiation. Furthermore, animal studies demonstrated that the SalB-loaded hydrogel not only stimulated new bone formation but also mitigated bone loss and slowed the progression of osteoporosis. In conclusion, the CS/β-GP-SA hydrogel loaded with SalB holds promise as a therapeutic strategy for treating osteoporosis.