A collagen/alginate tissue-engineered Intervertebral disc for cervical total disc replacement - An in vivo study with dogs

用于颈椎间盘置换的胶原/藻酸盐组织工程椎间盘 - 犬体内研究

• 批准号: 313651170
• 负责人: Privatdozent Dr. Gernot Lang
• 金额: --
• 依托单位: Weill Cornell Brain and Spine Center
• 依托单位国家: 德国
• 项目类别: Research Fellowships
• 财政年份: 2016
• 资助国家: 德国
• 起止时间: 2015-12-31 至 2016-12-31
• 项目状态: 已结题
• 来源: https://gepris.dfg.de/gepris/projekt/313651170?language=en
• 关键词: collagen; alginate; tissue; engineered; Intervertebral

Disc degeneration in the cervical spine is a prevalent clinical predicament requiring surgery. Anterior cervical decompression and fusion, the commonly performed surgical procedure, poses risks for pseudoarthrosis and adjacent segment disease. Prosthetic total disc replacement devices have therefore been developed to maintain segmental mobility, but have failed to replicate the native characteristics of the normal IVD in respect to motion, stability, load bearing properties, and mechanical damping. As an alternative treatment, we have pioneered a tissue-engineered IVD (TE-IVD) using collagen and alginate constructs seeded with anulus fibrosus and nucleus pulposus cells. Our initial in vivo rat-tail spine study showed that the TE-IVD successfully integrated with host tissue, reaching analogous biochemical, biomechanical, and histological properties as the native IVD. Further, a 2-month in vivo pilot study was conducted on the beagle cervical spine model; dogs are an ideal translational model due to similarity in anatomical and biomechanical features of the human spine. Our implanted TE-IVDs remained viable in the disc space, engrafted into the host tissue, and partially maintained disc height. Few dogs even presented gradual maturation of the TE-IVD. Despite its promise, our study requires a long-term follow-up with sufficient sample size and an assessment of mechanical functionality of the treated discs. Further, due to the mechanical loading inherent in the beagle spine, disc height of treated segments was only 70% of that of healthy discs; the need for stiffer TE-IVDs is of concern. We recently discovered that TE-IVD stiffness can be significantly enhanced with in vitro mechanical conditioning at its cultivation. Mechanically loaded TE-IVDs may meet the higher requisite of a mobile spine segment, yielding better implant viability and segment functionality. In the present study, we will evaluate mechanically conditioned TE-IVDs implanted in 12 beagles that will undergo discectomy at both C3/4 and 4/5. A total of 24 experimental disc segments will be split into three groups: a) 8 solely discectomized control, b) 8 discs treated with unloaded or c) 8 mechanically loaded TE-IVDs. Qualitative and quantitative X-ray and MRI analyses will be conducted at 8, 16, and 24 weeks to monitor degenerative changes and progress of implanted disc growth. After 24 weeks, motion segments will be histologically and biomechanically assessed.

颈椎椎间盘退变是临床上普遍存在的难题，需要手术治疗。颈椎前路减压融合术是常见的外科手术，存在假关节和邻近节段疾病的风险。因此，已经开发了人工全间盘置换装置来维持节段移动性，但在运动、稳定性、承载特性和机械减震方面未能复制正常IVD的固有特征。作为另一种治疗方法，我们开创了一种组织工程化IVD(TE-IVD)，使用胶原和海藻酸盐构建，种植有纤维环和髓核细胞。我们最初的大鼠尾椎体内研究表明，TE-IVD成功地与宿主组织结合，达到了与天然IVD相似的生化、生物力学和组织学特性。此外，对Beagle颈椎模型进行了为期2个月的体内初步研究；由于狗的解剖学和生物力学特征与人类脊柱相似，因此狗是理想的翻译模型。我们植入的TE-IVD在椎间盘间隙中仍然存活，植入到宿主组织中，并部分保持了椎间盘高度。少数犬甚至出现了TE-IVD的逐渐成熟。尽管前景看好，但我们的研究需要有足够样本量的长期随访和对处理过的椎间盘的机械功能的评估。此外，由于Beagle脊柱固有的机械负荷，治疗节段的节段高度仅为健康节段的70%；需要更坚硬的TE-IVD是值得关注的。我们最近发现，在体外机械条件下，TE-IVD的硬度可以在其培养时显著增强。机械负荷的TE-IVD可以满足活动脊柱节段的更高要求，产生更好的植入生存能力和节段功能。在这项研究中，我们将评估在12只比格犬身上植入机械条件下的TE-IVD，这些犬将在C3/4和4/5同时接受椎间盘切除。总共24个实验节段将被分成三组：a)8个单纯摘除椎间盘的对照组，b)8个未加载的或c)8个机械加载的TE-IVD组。在8周、16周和24周将进行定性和定量的X射线和MRI分析，以监测植入的椎间盘的退变变化和进展。24周后，将对运动节段进行组织学和生物力学评估。