Meniscus Repair with a Novel Aligned Nanofiber Scaffold

为了增强膝关节炎的自然愈合过程，组织工程通过组织工程学产生新的组织。 细胞与生物可降解支架的组合。在最佳条件下， 工程将引导组织再生，并在愈合过程中提供机械支持， 过程使用静电纺丝工艺，可以产生随机的、非对齐的纳米纤维支架 由各种聚合物制成。这些网状物的纤维直径与天然细胞外基质的纤维直径相似。 细胞外基质（ECM），并支持多种细胞类型的附着和生长。这个过程可以进一步 修饰以产生具有限定的纤维排列的支架;从而产生多维的 用于定向组织生长的纳米纤维微图案。这样的支架具有可控的和 各向异性的机械性能，并可以直接细胞形态。本提案的总体目标是 是使用合理的设计原则，将弯月面的结构-功能关系结合起来， 改善自然修复过程。具体而言，我们建议应用一种新型的光纤对准 纳米纤维可生物降解支架用于半月板组织工程，并提出以下建议： 假设1：与非对齐结构相比，纤维对齐可生物降解纳米纤维网片 接种半月板纤维软骨细胞（MFC）或间充质干细胞（MSC）将维持其 组织成熟期间的各向异性机械性能和新沉积的ECM将与纤维对齐 方向这些对齐的网格将增强纤维软骨ECM的表达和沉积 分子（I型和II型胶原），并且这些构建体的所得拉伸性质将大于 即使在聚合物组分降解之后，也可以通过在非对齐的网格上生长的细胞实现。 假设2：随着新的基质沉积在天然组织和支架之间，支架的强度增加。 工程接口将增加。当使用与支架对齐的支架时，界面将更坚固。 天然组织纤维方向，界面ECM平行于天然纤维沉积。由于弯月面是 细胞减少，预先用MFC或MSC接种网将加速界面形成。预培养 在形成骨-支架复合物之前装载细胞的支架将进一步加速界面形成。 这些研究将验证一种假设，即新型纤维排列的可生物降解补片将增强 通过决定成形基质中的各向异性来提高工程化组织的质量。这项工作还将 证明通过纤维软骨细胞的预培养增强支架与天然组织的整合 在一个对齐的脚手架上最后，这些研究将为进一步探索机械 预处理的结构，将奠定基础，在体内动物研究，并将最终导致 临床应用新的修复策略，以恢复患者的功能与尿道撕裂。

To augment natural healing processes of the knee menisci, tissue engineering creates new tissues via the combination of cells with biodegradable scaffolds. Under optimal conditions, a scaffold for tissue engineering would guide tissue regeneration as well as provide mechanical support during the healing process. Using an electrospinning process, random, non-aligned, nanofibrous scaffolds may be created from a variety of polymers. These meshes have fiber diameters similar to that of the native extracellular matrix (ECM) and support the attachment and growth of a number of cell types. This process may be further modified to create scaffolds possessing a defined fiber alignment; thereby producing a multidimensional nanofibrous micro-pattern for directed tissue growth. Such scaffolds possess both controllable and anisotropic mechanical properties and can direct cellular morphology. The overall objective of this proposal is to use rational design principles that incorporate the structure-function relationships of the meniscus to improve upon natural repair processes. Specifically, we suggest the application of a novel fiber-aligned nanofibrous biodegradable scaffold for use in meniscus tissue engineering and propose the following: Hypothesis 1: Compared to non-aligned constructs, fiber-aligned biodegradable nanofibrous meshes seeded with meniscus fibrochondrocytes (MFCs) or mesenchymal stem cells (MSCs) will maintain their anisotropic mechanical properties during tissue maturation and newly deposited ECM will align with the fiber direction. These aligned meshes will enhance the expression and deposition of fibrocartilaginous ECM molecules (type I and II collagen) and the resulting tensile properties of these constructs will be greater than that achieved by cells grown on non-aligned meshes, even after the polymeric component has degraded. Hypothesis 2: As a new matrix is deposited between the native tissue and the scaffold, the strength of the engineered interface will increase. The interface will be stronger when utilizing scaffolds aligned with the native tissue fiber direction, with interracial ECM deposited parallel to native fibers. As the meniscus is hypocellular, prior seeding of meshes with MFCs or MSCs will expedite interface formation. Pre-culture of cell-laden scaffolds prior to forming meniscus-scaffold composites will further expedite interface formation. These studies will validate the hypothesis that novel fiber-aligned biodegradable meshes will enhance the quality of engineered meniscal tissue by dictating anisotropy in the forming matrix. This work will also demonstrate the enhancement of scaffold integration to native tissue via pre-culture of fibrocartilaginous cells on an aligned scaffold. Finally, these studies will define parameters for further explorations of mechanical preconditioning of constructs, will lay the groundwork for in vivo animal studies, and will ultimately lead to the clinical application of new repair strategies to restore function in patients with meniscal tears.