Nanofiber Scaffolds with Gradations in Mineral Content for Rotator Cuff Repair

描述（由申请人提供）：该多学科项目涉及来自华盛顿大学生物医学工程和矫形外科系的纳米技术和肌腱-骨测试、分析和手术应用方面的成熟和富有成效的专家。我们的目标是设计、制造和验证用于肩袖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性附着点。我们将采取仿生方法来解决这个问题，通过应用自然肌腱-骨插入的知识，通过静电纺丝从可生物降解的聚合物设计和制造新的生物可降解支架，然后用磷酸钙涂层连续渐变。该支架将与间充质干细胞（MSCs）结合，并植入我们完善的大鼠肩袖损伤和修复模型中，以促进肌腱-骨愈合。我们将开发的支架具有矿物质含量的梯度，以模拟天然插入部位，并可以作为移植物来引导体内组织再生，以实现肌腱-骨愈合。我们的长期目标是将这些支架用于临床环境中，成功修复软组织（半月板，韧带和软骨）与骨界面。本研究的范围包括：i）通过静电纺丝和生物矿化的组合来制造具有不同结构有序性和矿物质含量连续梯度的生物支架; ii）测试并然后优化用于肌腱-骨修复的梯度支架的机械性能; iii）检查并量化对梯度支架的细胞反应;和iv）确定矿物质梯度和MSC接种对腱-骨愈合的影响。 公共卫生相关性：我们将设计、制造和验证一类新型支架，该支架基于静电纺丝纳米纤维，并具有用于肩袖修复的连续分级的矿物质含量-即，将撕裂的肌腱手术重新附着到其骨插入处。这是一个临床上重要的问题，影响大约30%的60岁以上的人口。目前的失败率从30%到94%不等。降低这些失败率将对这些患者的肩关节功能产生重大影响。这项研究将改善肩袖损伤患者的健康和生活质量，对肩袖和其他软组织-骨界面疾病的治疗产生重大影响（例如，前交叉韧带重建）。

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).