Wang Huan, Li Moyan, Yang Jiaojiao, Liu Zhao, Shi Shijie, Liu Dachuan, Hong Youzhi, Liu Hongjian, Chen Songfeng, Li Jiyao, Chen Song, Li Bin
Medical 3D Printing Center, Orthopedic Institute, Department of Orthopedic Surgery, The First Affiliated Hospital, School of Basic Medical Sciences, Interdisciplinary Innovation Center for Nanomedicine, MOE Key Laboratory of Geriatric Diseases and Immunology, Suzhou Medical College, Soochow University, Suzhou, Jiangsu, 215000, China.
State Key Laboratory of Oral Diseases, National Clinical Research Center for Oral Diseases, West China Hospital of Stomatology, Sichuan University, Chengdu, 610041, China.
J Orthop Translat. 2025 Aug 29;55:62-74. doi: 10.1016/j.jot.2025.08.004. eCollection 2025 Nov.
Intervertebral disc (IVD) herniation is a major cause of low back pain and disability, with microdiscectomy being the standard surgical treatment. However, microdiscectomy fails to address annulus fibrosus (AF) defects, increasing the risk of recurrent herniation. Current therapeutic strategies for this condition remain limited in efficacy. The lack of repair following injury and unresolved inflammation can further damage the IVD function, ultimately leading to irreversible IVD degeneration. Therefore, the development of an AF adhesive capable of both mechanically stabilizing annular fissures and enabling localized anti-inflammatory drug delivery emerges as a promising strategy to address this clinical challenge.
The developed AF adhesive system, designated as STIG, is formulated from silk fibroin, tannic acid, ibuprofen, and guanidine hydrochloride (GuCl). A comprehensive evaluation is conducted on STIG, encompassing its microstructure, composition, injectability, tissue adhesion, rheological properties, and biocompatibility. To assess anti-inflammatory efficacy, an inflammatory microenvironment is established via lipopolysaccharide (LPS)-stimulated AF cells. For validation, a rat model of IVD degeneration is surgically induced through puncturing the AF to simulate nucleus pulposus (NP) herniation. This experimental framework enables evaluation of STIG's ability to prevent NP protrusion, modulate inflammatory responses, and delay IVD degeneration.
In the STIG system, GuCl serves the role of a hydrogen bond disruptor, facilitating its release into bodily fluids, which in turn allows for the reformation of hydrogen bonds. This property endows STIG with the ability to transition from an injectable, low-stiffness state to a high-stiffness adhesive gel upon contact with water. The inclusion of ibuprofen in the adhesive effectively curbs the production of inflammatory mediators and the breakdown of extracellular matrix constituents. In a rat tail model, STIG effectively preserves the NP water content, maintains the disc height index, and safeguards the structural integrity of the IVD post-surgery.
These findings highlight STIG's potential as a promising therapeutic solution for sealing AF fissures and preventing IVD degeneration.
STIG shows significant clinical potential in spinal surgery. It offers a novel approach to reduce the recurrence rate post-microdiscectomy and improving long-term patient outcomes.
椎间盘(IVD)突出是腰背痛和残疾的主要原因,显微椎间盘切除术是标准的外科治疗方法。然而,显微椎间盘切除术未能解决纤维环(AF)缺损问题,增加了复发疝的风险。目前针对这种情况的治疗策略疗效仍然有限。损伤后缺乏修复以及炎症未得到解决会进一步损害IVD功能,最终导致IVD不可逆转的退变。因此,开发一种既能机械稳定环形裂隙又能实现局部抗炎药物递送的AF粘合剂,成为应对这一临床挑战的有前景的策略。
所开发的AF粘合剂系统命名为STIG,由丝素蛋白、单宁酸、布洛芬和盐酸胍(GuCl)配制而成。对STIG进行了全面评估,包括其微观结构、组成、可注射性、组织粘附性、流变学性质和生物相容性。为了评估抗炎效果,通过脂多糖(LPS)刺激的AF细胞建立炎症微环境。为了进行验证,通过穿刺AF模拟髓核(NP)突出,手术诱导建立IVD退变大鼠模型。这个实验框架能够评估STIG预防NP突出、调节炎症反应和延缓IVD退变的能力。
在STIG系统中,GuCl起到氢键破坏剂的作用,促进其释放到体液中,进而允许氢键重新形成。这一特性使STIG在与水接触时能够从可注射的低硬度状态转变为高硬度的粘性凝胶。粘合剂中包含布洛芬可有效抑制炎症介质的产生和细胞外基质成分的分解。在大鼠尾部模型中,STIG在手术后有效保留NP水分含量,维持椎间盘高度指数,并保护IVD的结构完整性。
这些发现突出了STIG作为密封AF裂隙和预防IVD退变的有前景的治疗解决方案的潜力。
STIG在脊柱手术中显示出显著的临床潜力。它提供了一种新方法来降低显微椎间盘切除术后的复发率并改善患者的长期预后。