Meniscus Repair with a Novel Aligned Nanofiber Scaffold

为了增强膝关节半月板的自然愈合过程，组织工程通过

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.