Meniscus-Derived Matrix Scaffolds Promote the Integrative Repair of Meniscal Defects

Jacob C Ruprecht,Louis E Defrate,Taylor D Waanders,Amy L Mcnulty,J Brice Weinberg,James F Nishimuta,Christopher R Rowland,Katherine A Glass,Jennifer Stencel,Farshid Guilak

doi:10.1038/s41598-019-44855-3

Abstract

Meniscal tears have a poor healing capacity, and damage to the meniscus is associated with significant pain, disability, and progressive degenerative changes in the knee joint that lead to osteoarthritis. Therefore, strategies to promote meniscus repair and improve meniscus function are needed. The objective of this study was to generate porcine meniscus-derived matrix (MDM) scaffolds and test their effectiveness in promoting meniscus repair via migration of endogenous meniscus cells from the surrounding meniscus or exogenously seeded human bone marrow-derived mesenchymal stem cells (MSCs). Both endogenous meniscal cells and MSCs infiltrated the MDM scaffolds. In the absence of exogenous cells, the 8% MDM scaffolds promoted the integrative repair of an in vitro meniscal defect. Dehydrothermal crosslinking and concentration of the MDM influenced the biochemical content and shear strength of repair, demonstrating that the MDM can be tailored to promote tissue repair. These findings indicate that native meniscus cells can enhance meniscus healing if a scaffold is provided that promotes cellular infiltration and tissue growth. The high affinity of cells for the MDM and the ability to remodel the scaffold reveals the potential of MDM to integrate with native meniscal tissue to promote long-term repair without necessarily requiring exogenous cells.

Highlights

In this regard, tissue engineering approaches that use biomaterial scaffolds in combination with endogenous or exogenous cells provide a novel approach for biological repair of meniscal injuries[17,18]
The scaffolds were filled by endogenous meniscus cells migrating from the injured meniscus tissue or seeded with exogenous bone marrow-derived mesenchymal stem cells (MSCs)
Exogenous growth factors were not used, in order to evaluate the ability of endogenous cells or MSCs seeded on the meniscus-derived matrix (MDM) scaffolds to promote meniscus repair

Summary

Introduction

Tissue engineering approaches that use biomaterial scaffolds in combination with endogenous or exogenous cells provide a novel approach for biological repair of meniscal injuries[17,18]. Demineralized bone matrix has been used to enhance bone regeneration and repair[19], and a cartilage-derived matrix has been shown to promote neocartilage formation[20] These tissue-derived matrices direct stem cell differentiation towards a phenotype similar to the tissue of origin[21,22,23,24,25,26]. Tissue-derived scaffolds may contain natural growth factors localized to the ECM27 and may minimize the need for exogenous growth factor addition These scaffolds may promote cellular infiltration and tissue repair by enabling cells to interact with their native ECM components. The objective of this study was to use only physical disruption of porcine meniscus tissue to generate minimally processed meniscus-derived matrix (MDM) scaffolds and test their effectiveness in promoting integrative meniscus repair. We provide evidence that the MDM scaffold is a promising tool for integrative meniscus repair

Objectives

Methods

Results

Conclusion