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

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.