由椎间盘退变引起的下背痛是全球残疾的主要原因。然而,迄今为止,很少有针对病因的治疗方法无法修复椎间盘(IVD)。这项研究调查了可注射水凝胶(NPgel)的能力,在从简并椎间盘分离的组织外植体培养模型中,抑制分解代谢蛋白表达并促进人髓核(NP)细胞中的基质表达。此外,将NPgel注射到自然退化的整个人类椎间盘中的能力,对机械功能的影响,研究了加载过程中的抗挤出性。最后,在注射有或没有骨髓祖细胞的NPgel后,研究了在生理负荷的人体器官培养系统中潜在再生效应的诱导。将NPgel注射到自然退化的人IVD中,增加了椎间盘高度和杨氏模量,并且在挤出测试期间被保留。注射到尸体盘,然后在生理负荷下培养,增加MRI信号强度,恢复了自然的生物力学特性,并显示出合成代谢增加和分解代谢减少的证据,观察到组织整合。这些结果为支持使用NPgel作为椎间盘再生的可注射疗法的概念数据提供了必要的证据。重要性声明:由椎间盘退变引起的下背痛是全球残疾的主要原因。然而,迄今为止,很少有针对病因的疗法无法修复椎间盘。这项研究调查了人组织样品中可注射水凝胶系统(NPgel)的潜在再生特性。为了模拟人类体内条件和独特的IVD生态位,使用动态加载的完整人类椎间盘培养系统。NPgel改善了生物力学特性,MRI强度增加,退变程度降低。此外,NPgel通过椎间盘的天然细胞诱导基质产生并减少分解代谢因子。该手稿为NPgel作为椎间盘退变的再生生物材料的潜在用途提供了证据。
Low back pain resulting from disc degeneration is a leading cause of disability worldwide. However, to date few therapies target the cause and fail to repair the intervertebral disc (IVD). This study investigates the ability of an injectable hydrogel (NPgel), to inhibit catabolic protein expression and promote matrix expression in human nucleus pulposus (NP) cells within a tissue explant culture model isolated from degenerate discs. Furthermore, the injection capacity of NPgel into naturally degenerate whole human discs, effects on mechanical function, and resistance to extrusion during loading were investigated. Finally, the induction of potential regenerative effects in a physiologically loaded human organ culture system was investigated following injection of NPgel with or without bone marrow progenitor cells. Injection of NPgel into naturally degenerate human IVDs increased disc height and Young\'s modulus, and was retained during extrusion testing. Injection into cadaveric discs followed by culture under physiological loading increased MRI signal intensity, restored natural biomechanical properties and showed evidence of increased anabolism and decreased catabolism with tissue integration observed. These results provide essential proof of concept data supporting the use of NPgel as an injectable therapy for disc regeneration. STATEMENT OF SIGNIFICANCE: Low back pain resulting from disc degeneration is a leading cause of disability worldwide. However, to date few therapies target the cause and fail to repair the intervertebral disc. This study investigated the potential regenerative properties of an injectable hydrogel system (NPgel) within human tissue samples. To mimic the human in vivo conditions and the unique IVD niche, a dynamically loaded intact human disc culture system was utilised. NPgel improved the biomechanical properties, increased MRI intensity and decreased degree of degeneration. Furthermore, NPgel induced matrix production and decreased catabolic factors by the native cells of the disc. This manuscript provides evidence for the potential use of NPgel as a regenerative biomaterial for intervertebral disc degeneration.