08 May 2015

Bioactive hydrogel will restore cartilage tissue

Knee injuries spoil the lives of not only athletes, but also ordinary people who lead an active lifestyle. Existing surgical methods for repairing damaged cartilage are expensive, cause complications and often prove ineffective in the long run. Even after a successful operation, degeneration of cartilage tissue can continue and lead to the development of painful arthritis.

Researchers at the University of Iowa, working under the leadership of Dr. James Martin, hope to solve this problem with the help of a minimally invasive, practical and inexpensive approach they are developing, which consists in injecting a bioactive hydrogel into the damaged joint.

Earlier, the authors found so-called chondrogenic progenitor cells (CCP) in cartilage tissue, the maturation of which leads to the formation of new cartilage tissue. This finding was quite unexpected, as it refuted the generally accepted opinion that cartilage tissue is one of the few tissues of the human body that are not capable of self-healing.

The researchers also identified molecular signaling factors that attract these cells from the surrounding healthy tissue to the damaged areas and stimulate their transformation into new chondrocytes. One of these signals – stromal cell factor-1 (SDF1) – is a kind of driving beacon for chondrogenic progenitor cells.

As part of the experiment, the authors isolated fragments of cartilage tissue of the femoral joint of nine cows and cultivated them for 2 days in a special environment. After that, through holes with a diameter of 4 millimeters were made in the cartilage, which were filled with a hydrogel consisting of fibrin and hyaluronic acid and enriched with stromal cell factor-1. This caused the migration of chondrogenic progenitor cells into the damage zone, and the subsequent introduction of the transforming growth factor beta-1 into the culture medium ensured the maturation of these cells and the formation of new cartilage tissue that completely filled the defect.


Image obtained using a confocal microscope
demonstrates chondrogenic progenitor cells migrating to the area of cartilage damage
after the introduction of a hydrogel containing stromal cell factor-1. Photo: University of Iowa Health Care.

The new tissue was integrated into the main cartilage fragment without scarring, while it did not differ in structure and appearance from normal cartilage. At the same time, its mechanical strength was somewhat inferior to the strength of normal cartilage tissue, however, the authors believe that this problem can be solved with the help of physiotherapy procedures and physical exercises.

To transform the new approach into a therapy suitable for clinical use, researchers need to develop a gel that sequentially releases stromal cell factor-1, which attracts progenitor cells, and a growth factor that stimulates their maturation. They plan to test two technologies: the introduction of nanoplasmids into the gel that encode the genetic sequence of the necessary factors, or nanospheres loaded with these factors.

The start of preclinical studies of the developed technique on animal models is planned for the next year, and in five years the authors hope to prepare everything necessary for conducting clinical trials.

Article by Yin Yu et al. Use of Recombinant Human Stromal Cell–Derived Factor 1alfa–Loaded Fibrin/Hyaluronic Acid Hydrogel Networks to Achieve Functional Repair of Full-Thickness Bovine Articular Cartilage Via Homing of Chondrogenic Progenitor Cells published in the journal Arthritis & Rheumatology.

Evgeniya Ryabtseva
Portal "Eternal youth" http://vechnayamolodost.ru08.05.2015

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