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

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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.