Preclinical safety and feasibility of a bupivacaine-loaded hydrogel for pain relief after spinal surgery

Pain and side effects of analgesics hinder postoperative recovery after instrumented spine surgery. Current locoregional blocks and sustained-release formulations are limited by rapid systemic absorption. We evaluated the local and systemic safety of a bupivacaine-loaded hydrogel, co-implanted with pedicle screws, in a sheep spine surgery model. Gelatin-based ring-shaped hydrogels containing bupivacaine crystals (305 mg total) were implanted with screws in eight sheep (Group C). Control groups included screws only (Group A), screws with unloaded hydrogels (Group B), and subcutaneous (SC) bupivacaine infiltration (150 mg, Group D). Plasma drug levels, systemic safety parameters, and histological host reaction at 6 and 56 days were assessed. All animals recovered without complications. Group D showed a Cmax of 138.3 ± 68.5 ng/mL at 1 h, while Group C had a lower Cmax of 50.4 ± 24.5 ng/mL at 28 h. The elimination half-life (T1/2) in Group C was 6.5 times longer than in Group D (67.6 ± 15.6 vs. 10.7 ± 5.5 h). Histology showed no differences in host reaction between groups. In conclusion, bupivacaine-loaded hydrogel was well-tolerated locally and systemically, with prolonged drug release and lower systemic exposure than SC infiltration. This approach shows promise for sustained postoperative analgesia in spine surgery.