Potential implantable nanofibrous biomaterials combined with stem cells for subchondral bone regeneration

The treatment of osteochondral defects remains a challenge. Four scaffolds were produced using Food and Drug Administration (FDA)-approved polymers to investigate their therapeutic potential for the regeneration of the osteochondral unit. Polycaprolactone (PCL) and poly(vinyl-pyrrolidone) (PVP) scaffolds were made by electrohydrodynamic techniques. Hydroxyapatite (HAp) and/or sodium hyaluronate (HA) can be then loaded to PCL nanofibers and/or PVP particles. The purpose of adding hydroxyapatite and sodium hyaluronate into PCL/PVP scaffolds is to increase the regenerative ability for subchondral bone and joint cartilage, respectively. Humanbone marrow-derived mesenchymal stem cells (hBM-MSCs) were seeded on these biomaterials. The biocompatibility of these biomaterials in vitro and in vivo, as well as their potential to support MSC differentiation under specific chondrogenic or osteogenic conditions, were evaluated. We show here that hBM-MSCs could proliferate and differentiate both in vitro and in vivo on these biomaterials. In addition, the PCL-HAp could effectively increase the mineralization and induce the differentiation of MSCs into osteoblasts in an osteogenic condition. These results indicate that PCL-HAp biomaterials combined with MSCs could be a beneficial candidate for subchondral bone regeneration

Long-Lasting Visuo-Vestibular Mismatch in Freely-Behaving Mice Reduces the Vestibulo-Ocular Reflex and Leads to Neural Changes in the Direct Vestibular Pathway

International audienceCalibration of the vestibulo-ocular reflex (VOR) depends on the presence of visual feedback. However, the cellular mechanisms associated with VOR modifications at the level of the brainstem remain largely unknown. A new protocol was designed to expose freely behaving mice to a visuo-vestibular mismatch during a 2-week period. This protocol induced a 50% reduction of the VOR. In vivo pharmacological experiments demonstrated that the VOR reduction depends on changes located outside the flocculus/paraflocculus complex. The cellular mechanisms associated with the VOR reduction were then studied in vitro on brainstem slices through a combination of vestibular afferent stimulation and patch-clamp recordings of central vestibular neurons. The evoked synaptic activity demonstrated that the efficacy of the synapses between vestibular afferents and central vestibular neurons was decreased. In addition, a long-term depression protocol failed to further decrease the synapse efficacy, suggesting that the VOR reduction might have occurred through depression-like mechanisms. Analysis of the intrinsic membrane properties of central vestibular neurons revealed that the synaptic changes were supplemented by a decrease in the spontaneous discharge and excitability of a subpopulation of neurons. Our results provide evidence that a long-lasting visuo-vestibular mismatch leads to changes in synaptic transmission and intrinsic properties of central vestibular neurons in the direct VOR pathway. Overall, these results open new avenues for future studies on visual and vestibular interactions conducted in vivo and in vitro

Advanced nanostructured medical device combining mesenchymal cells and VEGF nanoparticles for enhanced engineered tissue vascularization.

AIM: Success of functional vascularized tissue repair depends on vascular support system supply and still remains challenging. Our objective was to develop a nanoactive implant enhancing endothelial cell activity, particularly for bone tissue engineering in the regenerative medicine field. MATERIALS & METHODS: We developed a new strategy of tridimensional implant based on cell-dependent sustained release of VEGF nanoparticles. These nanoparticles were homogeneously distributed within nanoreservoirs onto the porous scaffold, with quicker reorganization of endothelial cells. Moreover, the activity of this active smart implant on cells was also modulated by addition of osteoblastic cells. RESULTS & CONCLUSION: This sophisticated active strategy should potentiate efficiency of current therapeutic implants for bone repair, avoiding the need for bone substitutes

Propriétés électrophysiologiques intrinsèques et modélisation des neurones responsables de l'intégration mathématique dans le noyau prepositus hypoglossi

Cette thèse concerne les mécanismes neuronaux impliqués dans l intégration mathématique d un signal de vitesse en signal de position. Dans le cadre du contrôle des mouvements horizontaux de l œil, cette intégration est réalisée par les neurones du noyau prepositus hypoglossi (nNPH). Les nNPH ont été classés, selon leur profil électrophysiologique, en 3 types (A, B et D) et modélisés. Contrairement aux neurones de type A et B présents aussi dans les noyaux vestibulaires médian et latéral, les neurones de type D sont spécifiques du NPH et leur potentiel de membrane présente des oscillations. De plus, la conductance sodique persistante est cruciale pour l électrophysiologie de tous les nNPH, quoique son impact et sa localisation diffèrent selon les types cellulaires. Enfin, les propriétés intrinsèques des neurones du NPH et des noyaux vestibulaires ont été comparées afin de comprendre le lien entre les fonctions de ces noyaux et les propriétés intrinsèques spécifiques de leurs neurones.The rationale behind this thesis is the understanding of the neural mechanisms involved in the mathematical integration of a velocity signal into a position signal. For eye movements in the horizontal plane, neurons of the prepositus hypoglossi nucleus (PHNn) are responsible for this integration. Here, PHNn have been classified in 3 types (A, B and D) according to their electrophysiological profile and then modeled. Unlike type A and B neurons, which are also found in the medial and lateral vestibular nuclei, type D neurons are specific to the NPH and their membrane potential shows subthreshold oscillations. Besides, persistent sodium conductance is crucial to the electrophysiology of the PHNn, however its impact and location are type-dependant. The intrinsic properties of neurons of the PHN and the vestibular nuclei have been compared to understand the link between the functions of these nuclei and the specific intrinsic properties of their respective neurons.PARIS-BIUSJ-Thèses (751052125) / SudocPARIS-BIUSJ-Physique recherche (751052113) / SudocSudocFranceF