Extracellular matrix – the key to biological knee repair?

Doctors at the University of Missouri are examining how  tissue-derived extracellular matrix (ECM) can help biologically repair a damaged knee. Extracellular matrix is  a secretion by cells that helps rebuild cartilage.

Chondrocytes are cells that are the building blocks of cartilage. Imagine a brick wall that has a hole in it. Our body calls the chondrocytes to the area where the wall needs to be patched. The Chondrocytes are the bricks. The bricks are useless without mortar to hold them in place. So the chondrocytes secrete an extracellular matrix, their own mortar.

So imagine again, the bricks arrive at the hole in the wall, secret its own mortar, joins with other bricks doing the same thing and the wall itself is sending signals to the bricks where they need to line up for a good patch fit.

Back to the doctors in Missouri. They cite that despite advances in orthopaedic surgery, effective treatments for cartilage and meniscus injuries remain a common and significant clinical challenge. Biological scaffolds derived from cell and tissue-derived extracellular matrix (ECM) have shown great promise in tissue engineering given the critical role of the ECM for maintaining the biological and biomechanical properties, structure, and function of native tissues.1

The problems with Extracellular matrix outside of its natural environment

At the University of Pittsburgh doctors examined the xxtracellular matrix of the meniscus and discovered some problems:

The inner region of the knee meniscus is frequently injured and possesses a poor intrinsic healing capacity. Solubilized extracellular matrix derived from decellularized (made neutral) meniscus tissue may promote a homologous or similar growth of progenitor cells (building blocks), thereby enhancing fibrocartilage formation within a meniscal lesion.

However, the meniscus possesses regional variation in ultrastructure, biochemical composition, and cell phenotype, which may affect the bioactivity of soluble ECM derived from different regions of decellularized menisci.2

The Pittsburgh doctors found that the ECM was region-specific and scaffold building could be problematic unless the ECM stayed within its particular meniscus region.

1 Tissue-Derived Extracellular Matrix Bioscaffolds: Emerging Applications in Cartilage and Meniscus Repair.
Monibi FA, Cook JL. Tissue-Derived Extracellular Matrix Bioscaffolds: Emerging Applications in Cartilage and Meniscus Repair. Tissue Eng Part B Rev. 2017 Feb 7. doi: 10.1089/ten.TEB.2016.0431. [Pubmed]

2 Rothrauff BB, Shimomura K, Gottardi R, Alexander PG, Tuan RS. Anatomical region-dependent enhancement of 3-dimensional chondrogenic differentiation of human mesenchymal stem cells by soluble meniscus extracellular matrix. Acta Biomater. 2017 Feb;49:140-151. [Pubmed]