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.

项目摘要 半月板眼泪是最常见的膝盖受伤，大约有100万手术涉及 半月板在美国每年进行。组织工程和再生医学方法是 积极追求克服当前临床治疗的局限性的潜在替代方法。但是， 这些方法对临床应用的翻译受到了有效的有效能力和有限的能力的阻碍 可重复创建具有各向异性结构和机械性能的生理大小的支架 ECM提供的本地弯孔和区域特异性生物线索的顺序。总体目标 提案是1）开发脚手架，该支架概括了复杂的结构和机械特征 半月板在多个尺度上，并结合了区域特异性的ECM线索和2）评估长期功能 这种脚手架及其在体内预防联合变性的能力。我们将使用新的高通量混合动力 3D熔体吹（3DMB）与溶液吹动（SB）协同整合的方法 传统非织造技术和3D打印的属性，以创建具有宏几何的脚手架， 纤维微体系结构和区域生物学提示（Meniscus衍生的ECM（MECM））以与本机相匹配 半月板。我们假设生物力学和MECM提示都必须与弯月面相似 获得优质的体内结局，主要是减少软骨变性。目标1是确定主要 3DMB和SB过程变量影响了结构结构和生物力学特性 由选定的生物聚合物和MECM制成的解剖尺寸弯曲脚架。目标2是确定是否 区域特异性MECM的掺入可改善细胞以及整合的浸润和组织形成 与周围的半月板组织。 AIM 3是确定部分后软骨变性 通过在脚手架中添加适当的MECM公式，降低了半月板切除术 拟态匹配的力学。完成后，该项目将提供有关微观的基本知识 与拟南芥相关的生物活性支架中的宏观过程结构函数关系 使用我们的新非织造方法，并将作为具有重要意义的基础技术，允许进步 在治疗骨科纤维软组织损伤中。

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.