Innovative concept for knee cartilage treatment

In order to regenerate, knee cartilage, paradoxically, needs to be placed under mechanical stress, as happens whenever we take a step and our knees take our weight. When stimulated in this way, the cartilage cells develop receptors that are sensitive to the growth factors produced by the organism.

It is also at this very moment that they would be most receptive to medication. Working on this basis, Dominique Pioletti and Harm-Anton Klok from EPF Lausanne have developed a smart material that only releases a substance when the material is mechanically loaded.

Threshold effect
As they describe in a recent publication (*), their material takes the form of a hydrogel matrix, liposome-type nanoparticles and, finally, a payload – in this case a dye. When subjected to cyclic mechanical loading, the hydrogel matrix heats up. Once subjected to heat, the diameter of the liposomes shrinks significantly. This frees up space in the matrix, increasing its permeability and facilitating the release of the dye from the matrix. “One of the main difficulties has been the development of nanoparticles that respond to our specification,” explains Dominique Pioletti. “Basically, for the concept to work, their response to the heating process must have a very clear threshold between the two to three degrees that separate the static and stimulated states.”

The researchers then wanted to verify that it was actually the heating process resulting from the repetition of the mechanical loading that caused the dye to be released. During an initial experiment, the material was subjected to cyclic mechanical loading but the heat produced was evacuated in order to prevent any local temperature increase in the material. “This test enabled us to exclude a sponge-type function, whereby the dye was only being released as a result of the pressure,” explains Dominique Pioletti. During a second experiment, the nanoparticles were removed. The matrix heated up as expected due to the cyclic mechanical loading but none of the dye was released. The researchers concluded that the three elements of the composite material were required for the system as a whole to function as intended.

Long-term prospects
Whilst the researchers have been able to demonstrate the validity of their concept, Dominique Pioletti stresses that a future treatment is still a long way off. “First of all we need to develop a hydrogel and nanoparticles that are safe and biodegradable, before progressing to clinical trials. And, above all, we need to find partners interested in investing in our project.”
National Research Programme “Smart Materials” (NRP 62)
NRP 62 is a cooperation programme between the Swiss National Science Foundation (SNSF) and the Innovation Promotion Agency (CTI). The programme's aim is not only to promote scientific excellence but also to promote the successful industrial exploitation of smart materials and their application. NRP 62 also strives to link up the available skills and resources of various research institutions in Switzerland. The research work provides the technologies required to develop smart materials and the structures needed to integrate these. Having started its second phase at the beginning of 2013, NRP 62 now consists of 14 projects whose funding has been continued thanks to their high potential for practical application. NRP 62 will come to an end in 2015.
(*)Mohamadreza Nassajian Moghadam, Vitaliy Kolesov, Arne Vogel, Harm-Anton Klok and Dominique P. Pioletti (2013). Controlled release from a mechanically-stimulated thermosensitive self-heating composite hydrogel. Biomaterials online: doi: 10.1016/j.biomaterials.2013.09.065

(available in pdf format from the SNSF to media representatives only: com@snf.ch)

Contact
Prof. Dominique P. Pioletti
Laboratory of Biomechanical Orthopedics
EPFL
CH-1015 Lausanne
Phone: +41 21 693 83 41
E-mail: dominique.pioletti@epfl.ch
http://lbo.epfl.ch