Topographical assessment demonstrates tissue uniformity, while time-lapse analysis indicates significant changes by Day 12.

By Holly Ober

DAVIS, Calif., June 12, 2017. Scientists have known for 2,300 years that articular cartilage neither repairs itself nor regenerates with ease. “Cartilage, when once cut off, [does not] grow again,” observed Aristotle, the Greek philosopher and scientist, in the fourth century BC.  In the last fifty years, scientists have succeeded in creating tissue that closely resembles native cartilage, but the engineered tissue lacks the tensile values required to endure the natural strains it would encounter when implanted in human joints to replace damaged cartilage. Scientists have tried chemical stimulation, as well as mechanical stimulation in the form of compression, hydrostatic pressure or shear, to mimic the kinds of biomechanical forces that help produce strong cartilage in the growing body, with mixed results.

Now, for the first time, a group of biomedical engineers at UC Davis has used tension successfully to produce cartilage with tensile properties at the level of native tissue. In a new paper published in Nature Materials, Jennifer Lee, Le Huwe, Nikolaos Paschos, Ashkan Aryaei, Courtney Gegg, Jerry Hu, and Kyriacos Athanasiou describe the creation of scaffold-free tissue that they placed in devices that stretched it gently lengthwise with intermittent and constant tension for five days. They found increases in tensile modulus and strength six (6) times those of untreated neocartilage, values at the levels of native cartilage. 

By not using a scaffold—an external framework within which cells develop into tissue—the stress reached the cells directly. Scaffolds often cause stress-shielding because the tension applied to the system is borne by the scaffold and not directly felt by the cells. When stress reached the cells without interference from a scaffold it helped produce much stronger tissue.

Morphological differences are present in week 4 neocartilage prior to in vivo implantation, as well as in CoTenS-treated tissues.

The Nature Materials paper comprises a series of sequential studies that first used animal and then human cells to demonstrate, both in the lab but also in a live system, that tension can drive exceptional tissue formation. The authors think the tension devices they invented could be used to strengthen other engineered tissues, such as ligament, tendon, muscle, or bone, whether they use scaffolds or not.


Paper published as:

Lee, J.K. (co-first); Huwe, L.Y. (co-first); Paschos, N.P.; Aryaei, A.; Gegg, C.; Hu, J.; Athanasiou, K.A.:  Tension stimulation drives tissue formation in scaffold-free systems, Nature Materials, 10.1038/nmat4917, 2017.