A Novel Gelatin Hydrogel-Based Drug-Delivery System Promotes Antimicrobial Efficacy in a Pyogenic Spondylodiscitis Rat Model.

Background: Spondylodiscitis/spondylitis is an intractable disease requiring long-term intravenous antibiotics administration. However, drug delivery is greatly restricted because of the avascular nature in the intervertebral disc, which not only delays recovery but increases antimicrobial resistance and osteomyelitis. The purpose of this study is to elucidate the efficacy of gelatin hydrogel microsphere incorporating cefazolin (GM-CEZ) using a rat spondylodiscitis model. Methods: First, GM-CEZ was characterized by in vitro degradability, sustainability, and antimicrobial effects. Second, its efficacy in vivo was evaluated using a rat spondylodiscitis model of bioluminescent methicillin-susceptible Results: In vitro, CEZ was gradually released with GM degradation and antimicrobial effects increased proportionally to the degradation. In vivo, single topical injection of GM-CEZ (1 mg GM, 250 μg/kg CEZ, 100 μL collagen) significantly reduced the amount of bacteria with fewer white blood cells 7 days after treatment and bone destruction 28 days after treatment, compared to local administration of CEZ (250 μg/kg) and systemic administration of CEZ (25 mg/kg/day for 28 days) (all, Conclusions: The local administration of GM-CEZ using a fraction of the systemic CEZ dose achieved enhanced antimicrobial effects without systemic and local toxicity, suggesting its potential as a promising treatment strategy for pyogenic spondylodiscitis.