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

项目摘要 半月板撕裂是最常见的膝关节损伤，大约有100万例手术， 在美国每年进行半月板手术。组织工程和再生医学方法是 作为克服当前临床治疗局限性的潜在替代方案而被积极追求。然而 这些方法向临床应用的转化受到其有效和有效地应用的能力有限的阻碍， 可重复地创建生理尺寸的支架，其具有各向异性的结构和机械性能， 由ECM提供的天然半月板和区域特异性生物线索的顺序。本项目的总体目标 建议是1）开发一种支架，其概括了 在多个尺度下观察半月板，并结合区域特异性ECM提示; 2）评估长期功能 以及它们在体内防止关节退化的能力。我们将使用一种新的高通量混合 3D熔体吹塑（3DMB）与溶液吹塑（SB）相结合的方法， 传统的非织造材料技术和3D打印的属性，以创建具有宏观几何形状的支架， 纤维微结构和带状生物学线索（拟南芥衍生的ECM（mECM）），以匹配天然的 弯月面我们假设生物力学和mECM提示都需要与半月板相似， 实现上级体内结果，主要是减少软骨退化。目标1是确定如何主要 3DMB和SB过程变量影响骨的结构架构和生物力学特性， 由选定的生物聚合物和mECM制成的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的掺入改善了细胞的浸润和组织形成以及整合 周围的半月板组织目的3是确定部分软骨损伤后是否发生软骨退变。 通过在支架内添加适当的mECM制剂减少了椎间盘切除术， 阿普丽尔斯匹配的机械师完成后，该项目将提供有关微观的基本知识， 和宏观层面的过程-结构-功能关系， 使用我们新的非织造布方法，并将作为一个具有重要意义的基础技术，允许进步 治疗骨科纤维性软组织损伤。

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.