I-Corps: Tissue-Engineered Intervertebral Disc with Biodegradable Cage

这个I-Corps项目的更广泛的影响/商业潜力是组织工程椎间盘的潜在开发，该组织工程椎间盘可能治疗间盘(IVD)退变。IVD变性是导致美国人残疾的主要原因之一。目前，腰椎间盘退变导致的慢性背痛每年造成1000亿美元的损失。此外，70岁患者高达60%的椎间盘严重退变，20岁患者20%的椎间盘有轻度退变迹象。随着全球中位年龄的快速增长，更多的人可能会遭受与IVD变性相关的衰弱疼痛。目前，有两种手术干预技术可用于治疗IVD退变，即椎间盘切除术和脊柱融合术。然而，这两种技术可能不能治疗疾病的根本原因，研究表明，这两种方法会导致相邻IVD的退化。这项拟议的技术可能会让患者和整形外科/神经外科医生都受益。患者可能会从令人衰弱的疼痛和经济负担中得到缓解。外科医生可能受益于简化的手术程序，最终减少手术时间和成本。这个i-Corps项目是基于组织工程(TE)椎间盘(IVD)的开发，该组织工程(TE)椎间盘(IVD)具有3-D打印的可生物降解的支架，以潜在地治疗椎间盘(IVD)退变。IVD是TE解决方案的候选方案之一，因为椎间盘组织在再生能力方面存在先天限制。所提出的技术是一种用于再生天然组织功能的TE IVD结构。最近的动物研究结果表明，它有可能治疗受损的静脉畸形。然而，复制天然组织的机械性能仍然是一个挑战。在植入的早期阶段，TE IVD结构没有足够的机械性能来承受体内的负荷。这种机械稳定性的缺乏会导致组织脱位和坍塌。然而，在植入早期存活下来的TE IVD构建物在体内成功整合。为了提供额外的机械支持，建议的技术包括一个3D打印的可生物降解的支架，该支架可以保护柔软的TE IVD构造，直到实现与宿主组织的整合，并且构造可以承受体内的负载。此外，为了最好地匹配单个患者的解剖几何形状，已经开发了一个有限元模型来潜在地预测体内的结构反应并优化笼子的拓扑结构。这一奖项反映了NSF的法定使命，并通过使用基金会的智力优势和更广泛的影响审查标准进行评估，被认为值得支持。

The broader impact/commercial potential of this I-Corps project is the potential development of a tissue-engineered intervertebral disc that may treat intervertebral disc (IVD) degeneration. IVD degeneration is one of the leading causes of disability among Americans. Currently, chronic back pain due to intervertebral disc degeneration costs US $100 billion per year. In addition, up to 60% of discs in 70-year-old patients have severely degenerated, and 20% of discs in 20-year-old patients have mild signs of degeneration. With the rapid increase in the global median age, a greater number of people could suffer debilitating pain related to IVD degeneration. Currently, there are two surgical intervention techniques available for IVD degeneration, discectomy and spinal fusion. However, these two techniques may not treat the underlying cause of the disease, and research indicates that these approaches lead to the degeneration of adjacent IVDs. The proposed technology may benefit both patients and orthopedic/neurosurgeons. Patients may be alleviated from the debilitating pain and the economic burden. Surgeons may benefit from simplified surgical procedures, ultimately reducing operative time and costs. This I-Corps project is based on the development of a tissue-engineered (TE) intervertebral disc (IVD) with a 3-D printed biodegradable cage to potentially treat intervertebral disc (IVD) degeneration. The IVD is an candidate for the TE solution, as the disc tissue has innate limitations to its regenerative capabilities. The proposed technology is a TE IVD construct to regenerate the function of the native tissue. Recent animal study results have shown its efficacy to potentially treat damaged IVDs. However, replicating the mechanical properties of the native tissue remains a challenge. In the early stages of implantation, TE IVD constructs do not have sufficient mechanical properties to withstand in vivo loads. Such a lack of mechanical robustness causes dislocation and collapse of the tissue. However, TE IVD constructs that survived the early implantation stage were successfully integrated in vivo. To provide extra mechanical support, the proposed technology includes a 3-D printed biodegradable cage that may protect the soft TE IVD constructs until integration with the host tissue is achieved and the constructs can withstand in vivo loads. In addition, to best match the anatomical geometry of individual patients, a finite element model has been developed to potentially predict the structural response in vivo and optimize the topology of the cage.This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.