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

该I-Corps项目更广泛的影响/商业潜力是可能治疗椎间盘（IVD）退变的组织工程椎间盘的潜在开发。IVD变性是美国人残疾的主要原因之一。目前，由于椎间盘退变引起的慢性背痛每年花费1000亿美元。此外，70岁患者中高达60%的椎间盘严重退变，20岁患者中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变性相关的衰弱性疼痛。目前，有两种手术干预技术可用于IVD退变，椎间盘切除术和脊柱融合术。然而，这两种技术可能无法治疗疾病的根本原因，研究表明这些方法会导致相邻IVD的退化。所提出的技术可能使患者和骨科/神经外科医生受益。患者可能会减轻衰弱的疼痛和经济负担。外科医生可以从简化的外科手术中受益，最终减少手术时间和成本。这个I-Corps项目是基于开发一种组织工程（TE）椎间盘（IVD），该椎间盘具有3D打印的可生物降解融合器，可潜在地治疗椎间盘（IVD）退变。IVD是TE解决方案的候选者，因为椎间盘组织对其再生能力具有先天限制。所提出的技术是一种TE IVD结构，用于再生天然组织的功能。最近的动物研究结果表明，其有效性可能治疗受损的IVD。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载荷。这种机械坚固性的缺乏导致组织的错位和塌陷。然而，在早期植入阶段存活的TE IVD结构在体内成功整合。为了提供额外的机械支持，申报技术包括一个3D打印的可生物降解融合器，可以保护软TE IVD结构，直到实现与宿主组织的整合，并且结构可以承受体内载荷。 此外，为了最好地匹配个体患者的解剖几何结构，开发了一个有限元模型，以预测体内结构反应并优化融合器的拓扑结构。该奖项反映了NSF的法定使命，并通过使用基金会的知识价值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.