Thierry Rouillon

Phosphate is a specific signal for ATDC5 chondrocyte maturation and apoptosis-associated mineralization: possible implication of apoptosis in the regulation of endochondral ossification

Involvement of Pi and Ca in chondrocyte maturation was studied because their levels increase in cartilage growth plate. In vitro results showed that Pi increases type X collagen expression, and together with Ca, induces apoptosis‐associated mineralization, which is similar to that analyzed in vivo, thus suggesting a role for both ions and apoptosis during endochondral ossification.

Carotid and femoral atherosclerotic plaques show different morphology

OBJECTIVE Results of endovascular repair vary according to the arterial bed. We hypothesized that these differences may be related to the plaque features. To explore this hypothesis, we designed a prospective study that compared carotid and femoral atheroma. METHODS AND RESULTS Patients that underwent femoral or carotid endarterectomy were included in our study. Demographic data and blood sampling were obtained prior to surgery. Plaques were evaluated for AHA grading, calcification and lipid content. Eighty-eight plaques were harvested during this study (45 carotid specimens and 43 femoral specimens). No differences were noted between carotid and femoral groups regarding demographic and biological data. Histological data more frequently showed fibrous cap atheroma in carotid arteries (75%) and fibrocalcific plaques in femoral arteries (93%), p<0.001. Morphological analyses showed a high prevalence of osteoid metaplasia in femoral arteries (63%) compared to carotid arteries (20%, p<0.001). Biochemical analyses were consistent with histological data, showing higher calcium and lesser cholesterol concentrations in femoral than in carotid plaques (p<0.01). CONCLUSIONS Femoral and carotid plaques showed different morphology in comparable groups of patients.

Laponite nanoparticle-associated silated hydroxypropylmethyl cellulose as an injectable reinforced interpenetrating network hydrogel for cartilage tissue engineering

Articular cartilage is a connective tissue which does not spontaneously heal. To address this issue, biomaterial-assisted cell therapy has been researched with promising advances. The lack of strong mechanical properties is still a concern despite significant progress in three-dimensional scaffolds. This articles objective was to develop a composite hydrogel using a small amount of nano-reinforcement clay known as laponites. These laponites were capable of self-setting within the gel structure of the silated hydroxypropylmethyl cellulose (Si-HPMC) hydrogel. Laponites (XLG) were mixed with Si-HPMC to prepare composite hydrogels leading to the development of a hybrid interpenetrating network. This interpenetrating network increases the mechanical properties of the hydrogel. The in vitro investigations showed no side effects from the XLG regarding cytocompatibility or oxygen diffusion within the composite after cross-linking. The ability of the hybrid scaffold containing the composite hydrogel and chondrogenic cells to form a cartilaginous tissue in vivo was investigated during a 6-week implantation in subcutaneous pockets of nude mice. Histological analysis of the composite constructs revealed the formation of a cartilage-like tissue with an extracellular matrix containing glycosaminoglycans and collagens. Overall, this new hybrid construct demonstrates an interpenetrating network which enhances the hydrogel mechanical properties without interfering with its cytocompatibility, oxygen diffusion, or the ability of chondrogenic cells to self-organize in the cluster and produce extracellular matrix components. This composite hydrogel may be of relevance for the treatment of cartilage defects in a large animal model of articular cartilage defects. STATEMENT OF SIGNIFICANCE Articular cartilage is a tissue that fails to heal spontaneously. To address this clinically relevant issue, biomaterial-assisted cell therapy is considered promising but often lacks adequate mechanical properties. Our objective was to develop a composite hydrogel using a small amount of nano reinforcement (laponite) capable of gelling within polysaccharide based self-crosslinking hydrogel. This new hybrid construct demonstrates an interpenetrating network (IPN) which enhances the hydrogel mechanical properties without interfering with its cytocompatibility, O2 diffusion and the ability of chondrogenic cells to self-organize in cluster and produce extracellular matrix components. This composite hydrogel may be of relevance for the treatment of cartilage defects and will now be considered in a large animal model of articular cartilage defects.

A Cellulose/Laponite Interpenetrated Polymer Network (IPN) Hydrogel: Controllable Double-Network Structure with High Modulus

Laponite XLS™, which is a synthetic clay of nanometric dimensions containing a peptizing agent, has been associated with silanized hydroxypropylmethylcellulose (Si-HPMC) to form, after crosslinking, a novel composite hydrogel. Different protocols of sample preparation were used, leading to different morphologies. A key result was that the storage modulus of Si-HPMC/XLS composite hydrogel could be increased ten times when compared to that of pure Si-HPMC hydrogel using 2 wt % of Laponite. The viscoelastic properties of the composite formulations indicated that chemical and physical network structures co-existed in the Si-HPMC/XLS composite hydrogel. Images that were obtained from confocal laser scanning microscopy using labelled Laponite XLS in the composite hydrogels show two co-continuous areas: red light area and dark area. The tracking of fluorescent microspheres motions in the composite formulations revealed that the red-light area was a dense structure, whereas the dark area was rather loose without aggregated Laponite. This novel special double-network structure facilitates the composite hydrogel to be an adapted biomaterial for specific tissue engineering. Unfortunately, cytotoxicity’s assays suggested that XLS Laponites are cytotoxic at low concentration. This study validates that the hybrid interpenetrated network IPN hydrogel has a high modulus that has adapted for tissue engineering, but the cell’s internalization of Laponites has to be controlled.