Nanofiber Scaffolds with Gradations in Mineral Content for Rotator Cuff Repair

描述（由申请人提供）：这个多学科项目涉及来自华盛顿大学生物医学工程系和矫形外科的纳米技术、肌腱到骨骼的测试、分析和外科应用方面的成熟和富有成效的专家。我们的目标是设计、制造和验证用于肌腱套撕裂手术修复的新型纳米结构，以将撕裂的肌腱恢复到其骨插入处。我们将采用仿生方法解决这一问题，利用天然肌腱到骨插入的知识，通过静电纺丝设计和制造新型纳米纤维支架，该支架由可生物降解的聚合物制成，然后用磷酸钙连续分层涂覆。该支架将与间充质干细胞（MSCs）结合，并植入我们建立的大鼠肌腱套损伤修复模型中，以促进肌腱到骨的愈合。我们将开发的支架具有矿物质含量的等级，以模拟自然插入位置，并且可以作为移植物指导体内组织再生，以实现肌腱到骨的愈合。我们的长期目标是，这些支架将在临床环境中用于成功修复软组织（半月板-，韧带-和软骨-）到骨界面。本研究的范围包括：i)采用静电纺丝和生物矿化相结合的方法制备具有不同结构顺序和矿物含量连续梯度的纳米纤维支架；Ii)测试并优化分级支架用于肌腱-骨修复的力学性能；Iii)检测和量化细胞对分级支架的反应；iv)确定矿物梯度和MSCs播种对肌腱到骨愈合的影响。

DESCRIPTION (provided by applicant): This multidisciplinary program involves well-established and productive experts in nanotechnology and tendon-to-bone testing, analysis, and surgical application from Washington University's Departments of Biomedical Engineering and Orthopaedic Surgery. Our goal is to design, fabricate, and validate novel nanostructures for use in the surgical repair of rotator cuff tears to restore the torn tendon to its bony insertion. We will take a biomimetic approach to this problem by applying knowledge of the natural tendon-to-bone insertion to design and fabricate novel nanofiber scaffolds from a biodegradable polymer by electrospinning, followed by coating with calcium phosphate in a continuous gradation. The scaffolds will be combined with mesenchymal stem cells (MSCs) and implanted in our well-established rat rotator cuff injury-and-repair model to enhance tendon- to-bone healing. The scaffolds we will develop have gradations in mineral content to mimic the natural insertion site, and can serve as grafts to guide tissue regeneration in vivo for tendon-to-bone healing. Our long-term objective is that these scaffolds will be used in a clinical setting for successful repair of soft tissue (meniscus-, ligament-, and cartilage-) to bone interface. The scope of this research includes: i) Fabricating nanofiber scaffolds with different structural orders and continuous gradations in mineral content by a combination of electrospinning and biomineralization; ii) testing and then optimizing the mechanical properties of the graded scaffolds for use in tendon-to-bone repair; iii) examining and quantifying the cellular response to a graded scaffold; and iv) determining the effect of a mineral gradient and seeding of MSCs on tendon-to-bone healing. PUBLIC HEALTH RELEVANCE: We will design, fabricate, and validate a novel class of scaffolds based on electrospun nanofibers and with continuous gradations in mineral content for rotator cuff repair - that is, surgical reattachment of the torn tendons to their bony insertions. It is a clinically significant problem that affects approximately 30% of the population over the age of 60. The current failure rates range from 30% to 94%. Reducing these failure rates will have a major impact on shoulder function in these patients. This research will improve the health and quality of life for individuals afflicted with rotator cuff injuries, having significant impact on the treatment of diseases at rotator cuff and other soft tissue-to-bone interfaces (e.g., anterior cruciate ligament reconstruction).