Tiny beads used in new form of engineered cartilage
Injuries involving torn or degraded joint cartilage can be very debilitating, especially since that cartilage is incapable of healing itself, past a certain point. It's not surprising, therefore, that numerous scientists have been working on ways of either growing replacement cartilage outside of the body, or helping the body to regrow it internally. Just a few of the efforts have included things like stem cell-seeded bandages, bioactive gel, tissue scaffolds, and nanoscale stem cell-carrying balls. Now, researchers from Cleveland's Case Western Reserve University have announced something else that shows promise - sheets of mesenchymal (bone and cartilage-forming) stem cells, permeated with tiny beads filled with the growth factor beta-1.
The "traditional" approach to growing cartilage from a sheet of stem cells would involve soaking that sheet in a solution of the growth factor. Over time, that solution would cause the stem cells to differentiate into cartilage cells.
The Case Western team, however, chose to encapsulate the beta-1 in biodegradable gelatin microspheres, which were then distributed throughout the structure of the sheets. There are several advantages to introducing the growth factor in this way.
For starters, once the spheres degrade, they leave empty spaces between the cells. This creates a strong, scaffold-like structure, and allows the new cartilage to better retain water - the better that it can retain water, the more resilient it is to damage.
Also, the microspheres degrade at a controlled rate, when exposed to enzymes released by the stem cells. This means that cells throughout the sheet, inside and out, come into contact with the growth factor at about the same time, and thus the sheet forms into cartilage more uniformly.
Additionally, it is possible to tweak the microspheres' rate of degradation, by varying the amount of cross-linking in their molecular structure. To that end, the scientists tested separate sheets containing sparsely cross-linked and highly cross-linked beta-1-laden spheres. They also tried out sheets containing sparsely cross-linked spheres containing no beta-1, but that were soaked in a solution of it, instead.
All three types of sheets transformed into cartilage that was thicker and more resilient than that obtained from a solution-soaked control sheet containing no microspheres. The thickest cartilage, however, came from the sheet with the sparsely cross-linked beta-1-containing spheres. This was because the spheres degraded quicker than their highly cross-linked counterparts, providing the stem cells with a longer, more continuous exposure to the growth factor.
The tissue created was similar to the articular cartilage found in the knee, although it wasn't as mechanically strong as the real thing. The Case Western scientists are now working on ways of toughening it up, so that it could one day find use in human patients. They believe that within just one or two weeks of being cultured, the sheets could be implanted in the body, where the mechanical forces of the joints would help build and strengthen the new cartilage.