Engineered knee cartilage goes anisotropic

New material is first to mimic the two-layered characteristics of native tissue

Original source: Physics World

Researchers in China have succeeded in engineering knee cartilage that, for the first time, mimics the anisotropic characteristic of native tissue. The fabrication technique employed, which involves simultaneously applying biochemical and biomechanical stimuli to stem cells seeded onto a biomimetic scaffold, causes fibrochondrocytes in the bioconstruct to differentiate into layers containing two types of collagen. When transplanted in the knee joints of rabbits the material not only improves tensile strength in the knee after 24 weeks but also reduces joint cartilage degradation.

Although tissue engineering has come along in leaps and bounds over the past decade, most techniques still cannot faithfully reproduce the anisotropic nature of physiological systems that consist of heterogenous masses of connective tissue cells and an extracellular matrix (ECM).

The knee meniscus, which is an example of an anisotropic tissue, is a pad of cartilage that absorbs shocks and protects the knee from friction. It cannot fully heal after being damaged or torn, so patients suffering from such injuries would benefit from transplants of a biomimetic cartilage material.

Complex structure

The structure of the knee meniscus is complex however and is made up of outer and inner regions. In the outer region, fibroblast-like cells are contained with an ECM that is mainly made up of type I collagen, which makes the cartilage resistant to tensile loads. The inner region contains chondrocyte-like cells embedded within an ECM mainly made up of type II collagen and glycosaminoglycans, which make the tissue resistant to compression.

Until now, most tissue engineering techniques to reconstruct the knee meniscus were only able to produce homogenous issue. This tissue cannot withstand tensile or compressive stress and so degenerates over time.

Researchers led by Dong Jiang from the Institute of Sports Medicine of Peking University Third Hospital in China has now developed a technique in which they culture bone-marrow-derived mesenchymal stem cells (BMSCs) on a biomimetic scaffold. During the culture they apply two synergistic biochemical growth factors (cytokines) to the tissue and a loading system that simultaneously exerts both tensile and compressive stresses. The method induces the stem cells to differentiate into sperate layers of type I and type II collagen, thus mimicking the anisotropy in natural knee cartilage.

Jiang and colleagues say they have successfully tested their material on rabbits by transplanting it into the knee joints of the animals.

Long-term knee chondroprotection

“To our knowledge, ours is the first study to apply orchestrated biomechanical and biomechanical cues to make an anisotropic knee meniscus, as well as the first in vivo demonstration of an anisotropic-engineered meniscus for long-term knee chondroprotection,” says Jiang.

“Interestingly, our approach has an analogy in the Chinese idiom ‘Qin Se He Ming’, which describes the harmonious concerto produced by the two traditional musical instruments, Qin and Se,” he tells Physics World.  “The note produced by the instruments could be represented by the biochemical and biomechanical stimuli respectively. Here, the synergy between both promotes the proliferation and differentiation of the BMSCs and reconstructs the anisotropic structures of the knee meniscus.”

Full details of the research are reported in Science Translational Medicine 10.1126/scitranslmed.aao0750.