An optimal scaffold based strategy for in vivo repair of large bone defects and its associated problems is presented in this work. Three polymeric scaffolds produced by using an extrusion-based additive manufacturing system were examined in a rat critical bone defect model: scaffolds without cells, with undifferentiated Adipose-derived mesenchymal stem cells (ADSCs) and differentiated ADSCs (osteoblasts). Scaffolds with undifferentiated cells seem to be the best strategy as they exhibited around 22% more bone formation than natural bone healing, and around 15% more than the two other cases.Authors observed that scaffolds enabled cell migration and tissue formation. Results suggest that undifferentiated ADSCs strongly contribute to new bone formation with no rejection if scaffolds are used to support cell migration, proliferation and differentiation. Our long-term goal is to engineer high-quality cell seeded-scaffolds (autograft and allograft) for bone regeneration, mainly in elderly patients.
The spontaneous healing process of the tympanic membrane starts from the outer epithelial layer, with later healing of the lamina propria and the mucosal layer.
The genetic audiogenic seizure hamster (GASH:Sal) is a model of a form of reflex epilepsy that is manifested as generalized tonic-clonic seizures induced by external acoustic stimulation. The morphofunctional alterations in the auditory system of the GASH:Sal that may contribute to seizure susceptibility have not been thoroughly determined. In this study, we analyzed the olivocochlear efferent system of the GASH:Sal from the organ of Corti, including outer and inner hair cells, to the olivocochlear neurons, including shell, lateral, and medial olivocochlear (LOC and MOC) neurons that innervate the cochlear receptor. To achieve this, we carried out a multi-technical approach that combined auditory hearing screenings, scanning electron microscopy, morphometric analysis of labeled LOC and MOC neurons after unilateral Fluoro-Gold injections into the cochlea, and 3D reconstruction of the lateral superior olive (LSO). Our results showed that the GASH:Sal exhibited higher auditory brain response (ABR) thresholds than their controls, as well as absence of distortion-product of otoacoustic emissions (DPOAEs) in a wide range of frequencies. The ABR and DPOAE results also showed differences between the left and right ears, indicating asymmetrical hearing alterations in the GASH:Sal. These alterations in the peripheral auditory activity correlated with morphological alterations. At the cochlear level, the scanning electron microscopy analysis showed marked distortions of the stereocilia from basal to apical cochlear turns in the GASH:Sal, which were not observed in the control hamsters. At the brainstem level, MOC, LOC, and shell neurons had reduced soma areas compared with control animals. This LOC neuron shrinkage contributed to reduction in the LSO volume of the GASH:Sal as shown in the 3D reconstruction analysis. Our study demonstrated that the morphofunctional alterations of the olivocochlear efferent system are innate components of the GASH:Sal, which might contribute to their susceptibility to audiogenic seizures. This article is part of a Special Issue entitled "Genetic and Reflex Epilepsies, Audiogenic Seizures and Strains: From Experimental Models to the Clinic".
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