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December 02, 2011

Engineering cartilage replacements

Eben Alsberg at Case Western has made progress toward implantable replacement cartilage, holding promise for knees, shoulders, ears and noses damaged by osteoarthritis, sports injuries and accidents.

Self-assembling sheets of mesenchymal stem cells permeated with tiny beads filled with growth factor formed thicker, stiffer cartilage than previous tissue engineering methods.

"We think that the capacity to drive cartilage formation using the patient's own stem cells and the potential to use this approach without lengthy culture time prior to implantation makes this technology attractive," said Eben Alsberg

Jeon O, Powell C, Solorio L, Krebs MD, Alsberg E: Affinity-based growth factor delivery from biodegradable, photocrosslinked heparin-alginate hydrogels. Journal of Controlled Release (in press, 2011).

Lee JB, Jeong SI, Bae MS, Heo DN, Kim CH, Alsberg E, Kwon IK: Highly porous electrospun nanofibers enhanced by ultra-sonication for improved cellular infiltration. Tissue Engineering (in press, 2011).





The microspheres provide structure, similar to scaffolds, creating space between cells that is maintained after the beads degrade. The spacing results in better water retention – a key to resiliency.

The gelatin beads degrade at a controllable rate due to exposure to chemicals released by the cells. As the beads degrade, growth factor is released to cells at the interior and exterior of the sheet, providing more uniform cell differentiation into neocartilage.

The rate of microsphere degradation and, therefore, cell differentiation, can be tailored by the degree to which the microsphere are cross-linked. Within the microspheres, the polymer is connected by a varying number of threads. The more of these connections, or cross-links, the longer it takes for enzymes the cell secretes to enter and break down the material.

The researchers made five kinds of sheets. Those filled with: sparsely cross-linked microspheres containing growth factor, highly cross-linked microspheres containing growth factor, sparsely cross-linked microspheres with no growth factor, highly cross-linked microspheres with no growth factor, and a control with no microspheres. The last three were grown in baths containing growth factor.

After three weeks in a petri dish, all sheets containing microspheres were thicker and more resilient than the control sheet. The sheet with sparsely crosslinked microspheres grew into the thickest and most resilient neocartilage
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