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和整形外科系的纳米技术和肌腱到骨骼测试、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、制造和验证新的纳米结构，用于肩袖撕裂的外科修复，以恢复撕裂的肌腱到其骨质连接处。我们将采用仿生的方法来解决这个问题，应用自然肌腱到骨骼插入的知识，通过静电纺丝从可生物降解的聚合物设计和制造新型纳米纤维支架，然后在连续的渐变过程中涂覆磷酸钙。支架将与间充质干细胞(MSCs)结合，并植入我们建立的大鼠肩袖损伤修复模型中，以促进肌腱到骨的愈合。我们将开发的支架在矿物质含量上具有梯度，以模拟自然的植入部位，并可以作为移植物来引导体内组织再生，以实现肌腱到骨骼的愈合。我们的长期目标是将这些支架用于临床，成功修复软组织(半月板、韧带和软骨)与骨的界面。这项研究的范围包括：i)通过静电旋转和生物矿化相结合的方法制备具有不同结构顺序和连续矿物质含量梯度的纳米纤维支架；ii)测试并优化用于肌腱到骨修复的梯度支架的力学性能；iii)检测和量化分级支架的细胞响应；以及iv)确定矿物梯度和种植MSCs对肌腱到骨愈合的影响。 与公共健康相关：我们将设计、制造和验证一种新型的支架，这种支架基于电纺纳米纤维，具有连续的矿物质含量梯度，用于肩袖修复-即手术将撕裂的肌腱重新连接到它们的骨骼插入物上。这是一个临床上重要的问题，影响了大约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部功能产生重大影响。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与骨骼界面疾病的治疗(例如前十字韧带重建)具有重大影响。

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).