Oral Presentation 51st International Society for the Study of the Lumbar Spine Annual Meeting 2025

INTRODUCTION: Intradiscal Cutibacterium acnes is a risk factor for the occurrence of Modic type 1 changes (MC1) after microdiscectomy.¹  Intradiscal injection of C. acnes in rats resulted in disc degeneration and MC1-like marrow changes. Oral antibiotics (amoxicillin-clavulanate) have shown significant clinical benefits in MC1 patients.¹ Microdiscectomy may allow for intradiscal antibiotic application and prevent bacteria induced disc degeneration and MC1. Our goal is to stably secure local antibiotic delivery from a hydrogel and at the same time improve disc biomechanics and prevent re-herniation. Our approach combines an antibiotic-loaded hyaluronic acid-tyramine hydrogel (HA-Tyr) with annulus fibrosus repair using a mechanically interlocking patch (iPatch). Using this approach, we previously confirmed that medium viscous HA-Tyr (|G*| = 0.76 kPa) did not herniate and improved disc biomechanics (under review). This study aimed to test (i) the effect of antibiotic loading into HA-Tyr on rheological properties and (ii) antibacterial activity on Gram-positive and Gram-negative bacteria.

METHODS: HA-Tyr with the previously identified viscosity was loaded with amoxicillin/clavulanate, clindamycin, or doxycycline at concentrations of 0.1, 1.0, and 10.0 mg/ml. These antibiotics were chosen for their established use in chronic low back pain,² effective disc penetration,³ and broad-spectrum activity. Each antibiotic was tested individually alongside a hydrogel-only control. Rheological properties were evaluated through amplitude sweep tests using a rheometer (n=3 per group). Antibiotic release and antibacterial activity of the antibiotic-loaded HA-Tyr against Staphylococcus aureus, Escherichia coli, and C. acnes were evaluated using a zone of inhibition test. C. acnes, isolated from symptomatic human discs, was included due to its prevalence in herniated discs,¹ while S. aureus ATCC25923 and E. coli MG1655 represent bacterial categories, which differ in antibiotic susceptibility. Loaded hydrogels (n=5 each group) were placed on bacteria-inoculated agar plates, and inhibition zone diameters were measured to quantify antibacterial efficacy. One-way and two-way ANOVA assessed group differences, with α=0.05.

RESULTS: Amoxicillin/clavulanate reduced storage modulus of the HA-Tyr at 10.0 mg/ml (-77.7%; p=0.013) but not at lower concentrations. Doxycycline reduced storage modulus at 10.0 mg/ml (-98.4%, p=0.001) and 1.0 mg/ml (-71.4%, p=0.006). For clindamycin, structural integrity was maintained across all concentrations tested (Fig.1). For Gram-positive bacteria (S. aures and C. acnes), clindamycin was most effective and had largest zone of inhibition at all concentrations (Fig.2; Fig.3). Doxycyline was the least effective at all concentrations against the Gram-positive bacteria. For Gram-negative E. coli, amoxicillin/clavulanate and doxycycline exhibited superior antibacterial effects compared to clindamycin at all concentrations. Overall, zones of inhibition were largest for C. acnes and lowest for E. coli.

DISCUSSION: Clindamycin is the most suitable antibiotic to be incorporated into HA-Tyr hydrogels, because it did not change HA-Tyr storage modulus up to 10 mg/ml, and because it was the most effective in killing C. acnes and S. aureus, two known disc pathogens. Treating microdiscectomy patients with a medium-viscosity HA-Tyr hydrogel loaded with clindamycin and combined with iPatch annulus fibrosus repair might prevent bacteria-caused disc degeneration and MC1 while preventing re-herniation and improving disc biomechanics. Further translational research is both required and ongoing.