Engineering cartilage replacements

December 02, 2011

A lab discovery is a step 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, researchers at Case Western Reserve University have found. A description of the research is published in the Journal of Controlled Release.

"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, associate professor in the departments of Biomedical Engineering and Orthopaedic Surgery, and senior author of the paper.

Alsberg teamed with biomedical engineering graduate students Loran D. Solorio and Phuong N. Dang, undergraduate student Chirag D. Dhami, and Eran L. Vieregge, a student at Case Western Reserve School of Medicine.

The team put transforming growth factor beta-1 in biodegradable gelatin microspheres distributed throughout the sheet of stem cells rather than soak the sheet in growth factor.

The process showed a host of advantages, Alsberg said.

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.

The results indicate that the sparsely cross-linked microspheres, which degraded more rapidly by cell-secreted enzymes, provided a continuous supply of growth factor throughout the sheets that enhanced the uniformity, extent, and rate of stem cell differentiation into cartilage cells, or chondrocytes.

The tissue appeared grossly similar to articular cartilage, the tough cartilage found in the knee: rounded cells surrounded by large amounts of a matrix containing glycosaminoglycans. Called GAG for short, the carbohydrate locks water ions in the tissue, which makes the tissue pressure-resistant.

Testing also showed that this sheet had the highest amount of type II collagen - the main protein component of articular cartilage.

Although the sheet was significantly stiffer than control sheets, the mechanics still fell short of native cartilage. Alsberg's team is now working on a variety of ways to optimize the process and make replacement cartilage tough enough for the wear and tear of daily life.

One major advantage of this system is that it may avoid the troubles and expense of growing the cartilage fully in the lab over a long period of time, and instead permit implantation of a cartilage sheet into a patient more rapidly.

Because the sheets containing microspheres are strong enough to be handled early during culturing, the researchers believe sheets just a week or two old could be used clinically. The mechanical environment within the body could further enhance cartilage formation and increase strength and resiliency of the tissue, completing maturation.
-end-


Case Western Reserve University

Related Stem Cells Articles from Brightsurf:

SUTD researchers create heart cells from stem cells using 3D printing
SUTD researchers 3D printed a micro-scaled physical device to demonstrate a new level of control in the directed differentiation of stem cells, enhancing the production of cardiomyocytes.

More selective elimination of leukemia stem cells and blood stem cells
Hematopoietic stem cells from a healthy donor can help patients suffering from acute leukemia.

Computer simulations visualize how DNA is recognized to convert cells into stem cells
Researchers of the Hubrecht Institute (KNAW - The Netherlands) and the Max Planck Institute in Münster (Germany) have revealed how an essential protein helps to activate genomic DNA during the conversion of regular adult human cells into stem cells.

First events in stem cells becoming specialized cells needed for organ development
Cell biologists at the University of Toronto shed light on the very first step stem cells go through to turn into the specialized cells that make up organs.

Surprising research result: All immature cells can develop into stem cells
New sensational study conducted at the University of Copenhagen disproves traditional knowledge of stem cell development.

The development of brain stem cells into new nerve cells and why this can lead to cancer
Stem cells are true Jacks-of-all-trades of our bodies, as they can turn into the many different cell types of all organs.

Healthy blood stem cells have as many DNA mutations as leukemic cells
Researchers from the Princess Máxima Center for Pediatric Oncology have shown that the number of mutations in healthy and leukemic blood stem cells does not differ.

New method grows brain cells from stem cells quickly and efficiently
Researchers at Lund University in Sweden have developed a faster method to generate functional brain cells, called astrocytes, from embryonic stem cells.

NUS researchers confine mature cells to turn them into stem cells
Recent research led by Professor G.V. Shivashankar of the Mechanobiology Institute at the National University of Singapore and the FIRC Institute of Molecular Oncology in Italy, has revealed that mature cells can be reprogrammed into re-deployable stem cells without direct genetic modification -- by confining them to a defined geometric space for an extended period of time.

Researchers develop a new method for turning skin cells into pluripotent stem cells
Researchers at the University of Helsinki, Finland, and Karolinska Institutet, Sweden, have for the first time succeeded in converting human skin cells into pluripotent stem cells by activating the cell's own genes.

Read More: Stem Cells News and Stem Cells Current Events
Brightsurf.com is a participant in the Amazon Services LLC Associates Program, an affiliate advertising program designed to provide a means for sites to earn advertising fees by advertising and linking to Amazon.com.