Using 3D Nonwovens Fabrication to Engineer Region-Specific Extracellular Matrix Structure and Bioactivity of the Knee Meniscus

使用 3D 非织造布制造来设计膝关节半月板的区域特异性细胞外基质结构和生物活性

• 批准号: 10441557
• 负责人: Matthew B Fisher
• 金额: $ 41.76万
• 依托单位: NORTH CAROLINA STATE UNIVERSITY RALEIGH
• 依托单位国家: 美国
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-07-01 至 2026-06-30
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10441557
• 关键词: 3-Dimensional; 3D Print; Anatomy; Architecture; Behavior; Biological; Biomechanics; Biopolymers; Caliber; Cell Culture Techniques; Cell Differentiation process; Cell Survival; Cells; Characteristics; Clinical Treatment; Collagen; Complex; Control Groups; Cues; Data; Electrospinning; Engineering; Extracellular Matrix; Family suidae; Fiber; Formulation; Geometry; Goals; Hybrids; Implant; In Vitro; Infiltration; Injury; Intervertebral disc structure; Joints; Knee; Knee Injuries; Knowledge; Ligaments; Mechanics; Meniscus structure of joint; Modeling; Morphology; Operative Surgical Procedures; Orthopedics; Outcome; Patient-Focused Outcomes; Patients; Physiological; Polyesters; Polymers; Polyurethanes; Porosity; Process; Production; Property; Proteomics; Public Health; Regenerative Medicine; Reporting; Reproducibility; Research; Shapes; Soft Tissue Injuries; Stifle joint; Structure; Structure-Activity Relationship; Surgical sutures; Synovial Cell; System; Techniques; Technology; Tendon structure; Testing; Tissue Engineering; Tissues; Translations; Work; base; bioactive scaffold; cartilage degradation; clinical application; design; improved; in vivo; joint destruction; mechanical properties; melting; meniscal tear; meniscus injury; novel; prevent; repair model; repaired; scaffold; socioeconomics; three dimensional structure

PROJECT SUMMARY Meniscal tears are the most commonly reported knee injuries, and approximately 1 million surgeries involving the meniscus are performed annually in the US. Tissue engineering and regenerative medicine approaches are being actively pursued as potential alternatives to overcome limitations of current clinical treatments. Yet, the translation of these approaches to clinical application has been hampered by their limited ability to efficiently and reproducibly create physiologic-sized scaffolds featuring anisotropic structural and mechanical properties on the order of native meniscus and zone-specific biological cues provided by the ECM. The overall goals of this proposal are to 1) develop a scaffold that recapitulates the complex structural and mechanical characteristics of the meniscus at multiple scales and incorporates zone-specific ECM cues and 2) assess the long-term function of such scaffolds and their ability to prevent joint degeneration in-vivo. We will use a new high-throughput hybrid approach of 3D Melt Blowing (3DMB) in conjunction with Solution Blowing (SB) that synergistically integrates attributes of traditional nonwovens techniques and 3D printing to create a scaffold featuring macro-geometry, fibrous microarchitecture, and zonal biological cues (meniscus-derived ECM (mECM)) to match the native meniscus. We hypothesize that both biomechanics and mECM cues need to be similar to the meniscus to achieve superior in-vivo outcomes, primarily, reduced cartilage degeneration. Aim 1 is to determine how primary 3DMB and SB process variables influence the structural architecture and biomechanical properties of anatomically-sized meniscus scaffolds made of selected biopolymers and mECM. Aim 2 is to determine whether the incorporation of zone-specific mECM improves infiltration and tissue formation by cells as well as integration with the surrounding meniscus tissue. Aim 3 is to determine whether cartilage degeneration following partial meniscectomy is reduced through the addition of an appropriate mECM formulation within scaffolds with meniscus-matched mechanics. On completion, this project will provide fundamental knowledge about the micro- and macro-level process-structure-function relationships in meniscus-relevant bioactive scaffolds fabricated using our new nonwovens approach, and will serve as a base technology of great significance allowing advances in the treatment of orthopaedic fibrous soft tissue injuries.

项目概要 半月板撕裂是最常见的膝关节损伤，大约有 100 万例手术涉及 半月板检查每年在美国进行一次。组织工程和再生医学方法是 正在积极寻求作为克服当前临床治疗局限性的潜在替代方案。然而， 这些方法向临床应用的转化因其有效和有效的能力有限而受到阻碍。 可重复地创建具有各向异性结构和机械性能的生理尺寸支架 原生半月板的顺序和 ECM 提供的特定区域的生物线索。本次活动的总体目标 建议1）开发一种支架，概括复杂的结构和机械特性 多尺度的半月板并结合特定区域的 ECM 线索，2) 评估长期功能 这种支架及其预防体内关节退化的能力。我们将使用一种新的高通量混合 3D 熔喷 (3DMB) 与溶液吹塑 (SB) 相结合的方法，协同集成 传统非织造布技术和 3D 打印的属性来创建具有宏观几何形状的支架， 纤维微结构和区域生物线索（半月板衍生的 ECM (mECM)）以匹配天然 半月板。我们假设生物力学和 mECM 线索都需要与半月板相似才能 实现优异的体内结果，主要是减少软骨退化。目标 1 是确定主要程度 3DMB 和 SB 工艺变量影响结构体系和生物力学特性 由选定的生物聚合物和 mECM 制成的符合解剖学尺寸的半月板支架。目标 2 是确定是否 区域特异性 mECM 的结合改善了细胞的浸润和组织形成以及整合 与周围的半月板组织。目标3是确定部分软骨是否退化 通过在支架内添加适当的 mECM 制剂来减少半月板切除术 弯月面匹配力学。完成后，该项目将提供有关微观的基础知识 以及半月板相关生物活性支架的宏观过程-结构-功能关系 使用我们新的非织造布方法，并将作为具有重要意义的基础技术，推动进步 用于治疗骨科纤维软组织损伤。