Steverink Jasper G, Bruins Suzanne, van Tol Floris R, Jonkman Hein R, Amponsah Kwame B, Marvela Jessica, Smorenburg Andre J, Oosterman Bas J, Piluso Susanna, Verlaan Jorrit-Jan
SentryX B.V., Yalelaan 54, 3584CM, Utrecht, The Netherlands.
Department of Orthopaedics, University Medical Center Utrecht, Heidelberglaan 100, 3584CX, Utrecht, The Netherlands.
Sci Rep. 2025 Sep 2;15(1):32350. doi: 10.1038/s41598-025-17790-9.
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.
镇痛药的疼痛和副作用会阻碍脊柱器械手术后的恢复。目前的局部区域阻滞和缓释制剂受到快速全身吸收的限制。我们在绵羊脊柱手术模型中评估了与椎弓根螺钉共同植入的布比卡因负载水凝胶的局部和全身安全性。将含有布比卡因晶体（总量305mg）的明胶基环形水凝胶与螺钉一起植入8只绵羊体内（C组）。对照组包括仅植入螺钉（A组）、植入未负载水凝胶的螺钉（B组）和皮下（SC）注射布比卡因（150mg，D组）。评估了6天和56天时的血浆药物水平、全身安全性参数和组织学宿主反应。所有动物均顺利恢复，无并发症。D组在1小时时的Cmax为138.3±68.5ng/mL，而C组在28小时时的Cmax较低，为50.4±24.5ng/mL。C组的消除半衰期（T1/2）比D组长6.5倍（67.6±15.6对10.7±5.5小时）。组织学显示各组间宿主反应无差异。总之，布比卡因负载水凝胶在局部和全身耐受性良好，药物释放时间延长，全身暴露量低于SC注射。这种方法在脊柱手术术后持续镇痛方面显示出前景。
