Meniscus Repair with a Novel Aligned Nanofiber Scaffold

使用新型对齐纳米纤维支架修复半月板

• 批准号: 7446654
• 负责人: Robert L Mauck
• 金额: $ 6.86万
• 依托单位: UNIVERSITY OF PENNSYLVANIA
• 依托单位国家: 美国
• 财政年份: 2007
• 资助国家: 美国
• 起止时间: 2007-07-01 至 2011-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7446654
• 关键词: Animals; Anisotropy; Binding; Biochemical; Blood Vessels; Caliber; Cells; Cellular Morphology; Cicatrix; Collagen; Condition; Cultured Cells; Deposition; Engineering; Environment; Extracellular Matrix; Fiber; Gene Expression; Growth; Guided Tissue Regeneration; Healed; Knee; Lead; Mechanics; Meniscus structure of joint; Mesenchymal Stem Cells; Nature; Numbers; Patients; Pattern; Polymers; Process; Property; Radial; Relative (related person); Site; Structure; Structure-Activity Relationship; Time; Tissue Engineering; Tissues; Trauma; Work; articular cartilage; biodegradable polymer; cell type; clinical application; design; functional restoration; healing; improved; in vivo; interfacial; nanofiber; novel; preconditioning; repaired; scaffold; tissue support frame

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.

为了增强半月板的自然愈合过程，组织工程学通过 细胞与可生物降解支架的结合。在最佳条件下，组织支架 工程学将指导组织再生，并在愈合过程中提供机械支持 进程。使用电纺工艺，可以产生随机的、无排列的、纳米纤维支架 从各种聚合物中提取。这些网状物的纤维直径与天然细胞外的纤维直径相似 基质(ECM)，并支持多种细胞类型的附着和生长。这一过程可能会进一步 经修改以产生具有定义的纤维取向的支架；从而产生多维的 用于定向组织生长的纳米纤维微图案。这种支架具有可控性和可控性 各向异性的力学性能和可以直接指导细胞的形态。这项提案的总体目标是 是使用合理的设计原则，结合半月板的结构-功能关系来 改进自然修复过程。具体地说，我们建议应用一种新型的纤维定向 用于半月板组织工程的纳米纤维可生物降解支架，并提出如下建议： 假设1：与非排列结构相比，纤维排列的可生物降解的纳米纤维网 种植半月板纤维软骨细胞(MFC)或间充质干细胞(MSCs)将保持其 组织成熟过程中的各向异性机械性能和新沉积的ECM将与纤维对齐 方向。这些排列的网状物将促进纤维软骨细胞外基质的表达和沉积。 分子(I型和II型胶原)以及由此产生的这些构造物的拉伸性能将大于 这是通过生长在非排列网格上的细胞实现的，即使在聚合物成分已经降解之后也是如此。 假设2：当新的基质沉积在天然组织和支架之间时， 工程接口将增加。当使用与 天然组织纤维方向，界面ECM平行于天然纤维沉积。就像半月板 用MFC或MSCs预先播种低细胞的网状物将加速界面的形成。预培养 在形成半月板-支架复合材料之前，负载细胞的支架将进一步加速界面的形成。 这些研究将验证这样的假设，即新型纤维排列的生物可降解网状物将增强 通过规定形成基质中的各向异性来确定工程半月板组织的质量。这项工作还将 通过预培养纤维软骨细胞增强支架与天然组织的结合 在排列整齐的脚手架上。最后，这些研究将为进一步的力学探索确定参数 结构的预适应，将为体内动物研究奠定基础，并最终将导致 半月板撕裂患者修复功能新策略的临床应用