Department of Orthopaedic Surgery, McKay Orthopaedic Research Laboratory, University of Pennsylvania, Philadelphia, PA, USA.
Spine (Phila Pa 1976). 2010 Apr 15;35(8):867-73. doi: 10.1097/BRS.0b013e3181d74414.
To develop a construction algorithm in which electrospun nanofibrous scaffolds are coupled with a biocompatible hydrogel to engineer a mesenchymal stem cell (MSC)-based disc replacement.
To engineer a disc-like angle-ply structure (DAPS) that replicates the multiscale architecture of the intervertebral disc.
Successful engineering of a replacement for the intervertebral disc requires replication of its mechanical function and anatomic form. Despite many attempts to engineer a replacement for ailing and degenerated discs, no prior study has replicated the multiscale hierarchical architecture of the native disc, and very few have assessed the mechanical function of formed neo-tissues.
A new algorithm for the construction of a disc analogue was developed, using agarose to form a central nucleus pulposus (NP) and oriented electrospun nanofibrous scaffolds to form the anulus fibrosus region (AF). Bovine MSCs were seeded into both regions and biochemical, histologic, and mechanical maturation were evaluated with in vitro culture.
We show that mechanical testing in compression and torsion, loading methods commonly used to assess disc mechanics, reveal equilibrium and time-dependent behaviors that are qualitatively similar to native tissue, although lesser in magnitude. Further, we demonstrate that cells seeded into both AF and NP regions adopt distinct morphologies that mirror those seen in native tissue, and that, in the AF region, this ordered community of cells deposit matrix that is organized in an angle-ply configuration. Finally, constructs demonstrate functional development with long-term in vitro culture.
These findings provide a new approach for disc tissue engineering that replicates multi-scale form and function of the intervertebral disc, providing a foundation from which to build a multi-scale, biologic, anatomically and hierarchically relevant composite disc analogue for eventual disc replacement.
开发一种构建算法，将电纺纳米纤维支架与生物相容性水凝胶相结合，以构建基于间充质干细胞（MSC）的椎间盘替代物。
构建一种类似于盘状角层结构（DAPS）的结构，复制椎间盘的多尺度结构。
成功地对椎间盘进行替代需要复制其机械功能和解剖形式。尽管许多尝试对患病和退化的椎间盘进行替代物的工程设计，但没有之前的研究复制了天然椎间盘的多尺度分层结构，而且很少有研究评估形成的新组织的机械功能。
开发了一种新的椎间盘类似物构建算法，使用琼脂糖形成中央核髓（NP）和定向电纺纳米纤维支架形成纤维环区域（AF）。将牛 MSC 接种到这两个区域，并通过体外培养评估生化、组织学和机械成熟度。
我们表明，压缩和扭转的力学测试，是常用的评估椎间盘力学的方法，揭示了与天然组织具有定性相似但幅度较小的平衡和时变行为。此外，我们证明了接种到 AF 和 NP 区域的细胞采用与天然组织相似的形态，并且在 AF 区域，这些有序的细胞群会沉积以角层形式排列的基质。最后，构建体在长期的体外培养中显示出功能的发展。
这些发现为椎间盘组织工程提供了一种新的方法，可复制椎间盘的多尺度形态和功能，为构建最终用于椎间盘置换的多尺度、生物、解剖和层次相关的复合椎间盘类似物提供了基础。
