Department of Histology and Embryology, NMPA Key Laboratory for Safety Evaluation of Cosmetics, School of Basic Medical Sciences, Guangdong Provincial Key Laboratory of Bone and Joint Degeneration Diseases, The Third Affiliated Hospital of Southern Medical University, Southern Medical University, Guangzhou 510515, PR China.
Department of Histology and Embryology, NMPA Key Laboratory for Safety Evaluation of Cosmetics, School of Basic Medical Sciences, Guangdong Provincial Key Laboratory of Bone and Joint Degeneration Diseases, The Third Affiliated Hospital of Southern Medical University, Southern Medical University, Guangzhou 510515, PR China; Department of Plastic and Aesthetic Surgery, Nanfang Hospital of Southern Medical University, Guangzhou 510515, PR China.
Acta Biomater. 2024 Nov;189:116-129. doi: 10.1016/j.actbio.2024.09.038. Epub 2024 Oct 1.
Discectomy is the surgical standard of care to relieve low back pain caused by intervertebral disc (IVD) herniation. However, there remains annulus fibrosus (AF) defect and nucleus pulposus (NP) degeneration, which often result in recurrent herniation (re-herniation). Herein, we develop a polyphenol-modified waterborne polyurethane bioadhesives (PPU-glues) to promote therapy prognosis after discectomy. Being composed of tannic acid (TA) mixed cationic waterborne polyurethane nanodispersions (TA/WPU) and curcumin (Cur) embedded anionic waterborne polyurethane nanodispersions (Cur-WPU), PPU-glue gels rapidly (<10 s) and exhibits low swelling ratios, tunable degradation rates and good biocompatibility. Due to the application of an adhesion strategy combing English ivy mechanism and particle packing theory, PPU-glue also shows considerable lap shear strength against wet porcine skin (≈58 kPa) and burst pressure (≈26 kPa). The mismatched particle sizes and the opposite charges of TA/WPU and Cur-WPU in PPU-glue bring electrostatic interaction and enhance particle packing density. PPU-glue possesses superior reactive oxygen species (ROS)-scavenging capacity derived from polyphenols. PPU-glue can regulate extracellular matrix (ECM) metabolism in degenerated NP cells, and it can promote therapy biologically and mechanically in degenerated rat caudal discs. In summary, this study highlights the therapeutic approach that combines AF seal and NP augmentation, and PPU-glue holds great application potentials for post discectomy therapy. STATEMENT OF SIGNIFICANCE: Currently, there is no established method for the therapy of annulus fibrosus (AF) defect and nucleus pulposus (NP) degeneration after discectomy. Herein, we developed a polyphenol-modified biomimetic polyurethane bioadhesive (PPU-glue) with strong adhesive strength and superior bioactive property. The adhesion strategy that combined a particle packing theory and an English ivy mechanism was firstly applied to the intervertebral disc repair field, which benefited AF seal. The modified method of incorporating polyphenols was utilized to confer with ROS-scavenging capacity, ECM metabolism regulation ability and anti-inflammatory property, which promoted NP augmentation. Thus, PPU-glue attained the synergy effect for post discectomy therapy, and the design principle could be universally expanded to the bioadhesives for other surgical uses.
椎间盘切除术是治疗椎间盘（IVD）突出引起的腰痛的标准手术方法。然而，仍然存在纤维环（AF）缺陷和髓核（NP）退变，这常常导致复发的突出（再突出）。在此，我们开发了一种多酚改性的水性聚氨酯生物胶粘剂（PPU-胶），以促进椎间盘切除术后的治疗预后。PPU-胶由单宁酸（TA）混合阳离子水性聚氨酯纳米分散体（TA/WPU）和姜黄素（Cur）嵌入阴离子水性聚氨酯纳米分散体（Cur-WPU）组成，可快速（<10 s）凝胶化，并表现出低溶胀率、可调降解率和良好的生物相容性。由于应用了一种结合常春藤机制和颗粒堆积理论的粘附策略，PPU-胶对湿猪皮（≈58 kPa）和爆裂压力（≈26 kPa）也表现出相当大的搭接剪切强度。PPU-胶中的 TA/WPU 和 Cur-WPU 的粒径不匹配和电荷相反带来了静电相互作用并增强了颗粒堆积密度。PPU-胶具有源自多酚的优异活性氧物质（ROS）清除能力。PPU-胶可以调节退变 NP 细胞的细胞外基质（ECM）代谢，并可以在退变大鼠尾椎间盘中进行生物和机械治疗。总之，本研究强调了一种结合 AF 密封和 NP 增强的治疗方法，PPU-胶在后椎间盘切除术后治疗中具有巨大的应用潜力。意义声明：目前，尚无治疗椎间盘切除术后纤维环（AF）缺陷和髓核（NP）退变的既定方法。在此，我们开发了一种具有强粘附强度和优异生物活性的多酚改性仿生聚氨酯生物胶粘剂（PPU-胶）。首次将一种结合颗粒堆积理论和常春藤机制的粘附策略应用于椎间盘修复领域，有利于 AF 密封。利用多酚的改性方法赋予其 ROS 清除能力、ECM 代谢调节能力和抗炎特性，促进 NP 增强。因此，PPU-胶实现了椎间盘切除术后治疗的协同效应，设计原则可以普遍扩展到其他手术用途的生物胶粘剂。
