Nanofiber Scaffolds with Gradations in Mineral Content for Rotator Cuff Repair

用于肩袖修复的具有矿物质含量分级的纳米纤维支架

• 批准号: 8227988
• 负责人: Leesa M Galatz
• 金额: $ 44.49万
• 依托单位: GEORGIA INSTITUTE OF TECHNOLOGY
• 依托单位国家: 美国
• 财政年份: 2011
• 资助国家: 美国
• 起止时间: 2011-04-01 至 2016-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8227988
• 关键词: Adhesions; Affect; Age; Alkaline Phosphatase; Animal Model; Biomedical Engineering; Biomimetics; Bone Regeneration; Canis familiaris; Cartilage; Cells; Cereals; Clinic; Clinical; Collagen Fibril; Deposition; Disease; Extracellular Matrix; Failure; Fiber; Fibroblasts; Gene Expression; Glycolates; Goals; Guided Tissue Regeneration; Healed; Health; Human; Implant; In Vitro; Individual; Injury; Knowledge; Lead; Length; Ligaments; Maintenance; Mechanics; Meniscus structure of joint; Mesenchymal Stem Cells; Minerals; Modeling; Morphology; Nanostructures; Nanotechnology; Operative Surgical Procedures; Orthopedic Surgery procedures; Orthopedic Surgical Procedures; Osteoblasts; Patients; Population; Property; Quality of life; Rattus; Research; Rotator Cuff; Shoulder; Site; Stress; Tendon structure; Testing; Thick; United States Food and Drug Administration; Universities; Variant; Washington; anterior cruciate ligament reconstruction; base; biocompatible polymer; biodegradable polymer; biomineralization; bone; bone healing; calcium phosphate; cell motility; clinically relevant; clinically significant; density; design; ductile; healing; improved; in vivo; injury and repair; multidisciplinary; nanofiber; novel; programs; public health relevance; repaired; response; scaffold; scleraxis; soft tissue; supraspinatus muscle

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).

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骨科外科系的纳米技术和肌腱到骨测试、分析和外科应用方面成熟且富有成效的专家。我们的目标是设计、制造和验证新型纳米结构，用于肩袖撕裂的手术修复，以将撕裂的肌腱恢复到骨插入处。我们将采用仿生方法来解决这个问题，应用自然肌腱到骨骼插入的知识，通过静电纺丝设计和制造新型纳米纤维支架，然后用可生物降解的聚合物进行连续渐变的涂层。该支架将与间充质干细胞（MSC）结合并植入我们完善的大鼠肩袖损伤和修复模型中，以增强肌腱到骨骼的愈合。我们将开发的支架具有不同的矿物质含量，以模仿自然插入部位，并且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。我们的长期目标是这些支架将用于临床环境，成功修复软组织（半月板、韧带和软骨）与骨界面。本研究范围包括：i）通过静电纺丝和生物矿化相结合的方式制造具有不同结构顺序和矿物质含量连续梯度的纳米纤维支架； ii) 测试并优化用于肌腱-骨修复的分级支架的机械性能； iii) 检查和量化细胞对分级支架的反应； iv) 确定矿物质梯度和间充质干细胞接种对肌腱至骨骼愈合的影响。 公共健康相关性：我们将设计、制造和验证一类新型支架，该支架基​​于电纺纳米纤维和连续分级的矿物质含量，用于肩袖修复，即通过手术将撕裂的肌腱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 岁以上人群。目前的失败率在 30% 到 94% 之间。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的疾病（例如前十字韧带重建）的治疗产生重大影响。