15 December 2014

Meniscus from own stem cells on a biodegradable frame

Researchers at Columbia University Medical Center, working under the guidance of Professor Jeremy Mao, have developed a new method for replacing the meniscus of the knee joint using a personalized three–dimensional implant - a framework impregnated with human growth factors that stimulate the regeneration of articular connective tissue. Successfully tested on sheep, the approach may become the only effective method of repairing meniscus injuries diagnosed in millions of people every year.

Currently, small ruptures of the meniscus are surgically sutured. With more serious injuries, the meniscus has to be removed. This reduces pain manifestations and eliminates swelling of the knee joint, however, the absence of the meniscus, which is a natural shock absorber between the femur and tibia, significantly increases the risk of arthritis.

The damaged meniscus can be replaced with a transplant from connective tissue isolated from other parts of the patient's body or a cadaveric donor. However, this procedure has a very low success rate and is associated with significant risks for the patient.

The first stage of the new technology proposed by the authors is the use of magnetic resonance imaging to obtain images of the whole meniscus of a healthy knee. The resulting photos are converted into a three-dimensional image, which is used as a matrix for a three-dimensional printer that reproduces the shape of the meniscus with an accuracy of 10 micrometers. The process of printing the meniscus skeleton from the biodegradable polymer polycaprolactone, used for the manufacture of surgical suture material, takes only about 30 minutes.

From left to right: sheep meniscus; three-dimensional model of the meniscus;
anatomically correct meniscus skeleton printed with a three-dimensional printer.

Two recombinant human proteins are introduced into the framework: connective tissue growth factor (CTGF) and transforming growth factor-beta 3 (TGFbeta3). According to the data obtained by the authors, the sequential release of these proteins attracts stem cells and stimulates them to form new connective tissue.

For the correct formation of the meniscus, proteins must be released by certain regions of the skeleton in a strictly defined sequence. This is achieved by encapsulating proteins in two types of slowly dissolving polymer microspheres, first releasing connective tissue growth factor (stimulating the formation of the external meniscus), and subsequently transforming growth factor–beta 3 (stimulating the formation of the internal meniscus).

When implanting such a framework into the knee joints of sheep, the meniscus regeneration process took 4-6 weeks. Eventually, the framework dissolved and was excreted from the body.

In total, 11 sheep were involved in the study, whose knee joints are similar to human knee joints. The animals were randomly divided into 2 groups. A fragment of the meniscus of one of the knee joints of the animals of the experimental group was replaced with a growth factor-loaded skeleton, while the animals of the control group were implanted with skeletons that did not contain growth factors. After 3 months, the gait of the experimental group animals was fully restored. Postmortem analysis of the meniscus tissue of these animals showed that its structural and mechanical properties were almost similar to those of normal connective tissue of the meniscus. Currently, researchers are conducting experiments aimed at determining the durability of connective tissue formed at the site of the implanted skeleton.

Meniscus tissue formed at the site of implantation of a three-dimensional frame loaded with growth factors (right),
compared to the meniscus tissue of the control group animal (left).

The authors plan to start clinical trials as soon as they receive sufficient funding for their project. They assume that in the future, the production of a personalized frame, starting from the moment of magnetic resonance imaging of a healthy knee and ending with the delivery of the finished frame to the clinic, will take no more than a week.

Article by Chang H. Lee et al. Protein-Releasing Polymeric Scaffolds Induce Fibrochondrocytic Differentiation of Endogenous Cells for Knee Meniscus Regeneration in Sheep is published in the journal Science Translational Medicine.

Evgeniya Ryabtseva
Portal "Eternal youth" http://vechnayamolodost.ru based on the materials of Columbia University Medical Center:
Meniscus Regenerated with 3D-Printed Implant


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