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: 10640201
• 负责人: Matthew B Fisher
• 金额: $ 63.89万
• 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/10640201
• 关键词: 3-Dimensional; 3D Print; Anatomy; Architecture; Behavior; Biological; Biomechanics; Biopolymers; Cell Culture Techniques; Cell Differentiation process; Cell Survival; Cells; Characteristics; Clinical Treatment; Collagen; Complex; Control Groups; Cues; Data; Diameter; 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; Work; base; bioactive scaffold; cartilage degradation; clinical application; design; fabrication; improved; in vivo; joint destruction; mechanical properties; melting; meniscal tear; meniscus injury; novel; prevent; repair model; repaired; scaffold; socioeconomics; three dimensional structure; translational approach

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.

项目总结 半月板撕裂是最常见的膝关节损伤报告，约有100万例手术涉及 在美国，每年都会进行半月板手术。组织工程学和再生医学的方法是 被积极寻求作为潜在的替代方案，以克服目前临床治疗的局限性。然而， 将这些方法转化为临床应用一直受到它们有限的有效和 可重复创建具有各向异性结构和力学性能的生理大小支架 由ECM提供的本地半月板的顺序和特定区域的生物线索。这个项目的总体目标是 建议是1)开发一种支架，它概括了 半月板在多个尺度上，并结合区域特定的ECM提示和2)评估长期功能 这种支架及其在体内防止关节退变的能力。我们将使用一种新的高吞吐量混合动力车 三维熔体吹炼(3DMB)与溶液吹炼(SB)协同集成的方法 传统非织造布技术和3D打印的属性，以创建具有宏观几何特征的支架， 纤维微结构和带状生物线索(半月板衍生的ECM(MECM))以匹配本地 半月板。我们假设生物力学和MECM信号都需要类似于半月板 在体内实现更好的结果，主要是减少软骨退化。目标1是确定主要的 3DMB和SB工艺变量影响内固定器的结构和生物力学性能 由选定的生物聚合物和MECM制成的解剖大小的半月板支架。目标2是确定是否 区域特异性mECM的加入改善了细胞的渗透和组织形成以及整合 和周围的半月板组织。目的3是确定部分关节术后软骨退行性变 通过在支架内添加适当的mECM配方来减少半月板切除 半月面匹配的机械师。完成后，该项目将提供有关微型计算机的基础知识 制备的半月面相关生物活性支架的宏观工艺-结构-功能关系 使用我们新的非织造布方法，并将作为一项具有重要意义的基础技术，使之得以进步 在骨科纤维软组织损伤的治疗中。

项目成果

Multiphase CFD Modeling and Experimental Validation of Polymer and Attenuating Air Jet Interactions in Nonwoven Annular Melt Blowing.

• DOI: 10.1021/acs.iecr.2c01710
• 发表时间: 2022-09-21
• 期刊: INDUSTRIAL & ENGINEERING CHEMISTRY RESEARCH
• 影响因子: 4.2
• 作者: Schuchard, Karl G.;Pawar, Advay;Anderson, Bruce;Pourdeyhimi, Behnam;Shirwaiker, Rohan A.
• 通讯作者: Shirwaiker, Rohan A.