RESUMEN
Biomimetic bone tissue engineering strategies partially recapitulate development. We recently showed functional restoration of femoral defects using scaffold-free human mesenchymal stem cell (hMSC) condensates featuring localized morphogen presentation with delayed in vivo mechanical loading. Possible effects of construct geometry on healing outcome remain unclear. Here, we hypothesized that localized presentation of transforming growth factor (TGF)-ß1 and bone morphogenetic protein (BMP)-2 to engineered hMSC tubes mimicking femoral diaphyses induces endochondral ossification, and that TGF-ß1 + BMP-2-presenting hMSC tubes enhance defect healing with delayed in vivo loading vs. loosely packed hMSC sheets. Localized morphogen presentation stimulated chondrogenic priming/endochondral differentiation in vitro. Subcutaneously, hMSC tubes formed cartilage templates that underwent bony remodeling. Orthotopically, hMSC tubes stimulated more robust endochondral defect healing vs. hMSC sheets. Tissue resembling normal growth plate was observed with negligible ectopic bone. This study demonstrates interactions between hMSC condensation geometry, morphogen bioavailability, and mechanical cues to recapitulate development for biomimetic bone tissue engineering.
Asunto(s)
Huesos/metabolismo , Materiales Biocompatibles , Proteína Morfogenética Ósea 2/metabolismo , Regeneración Ósea/fisiología , Diferenciación Celular , Células Cultivadas , Condrogénesis/efectos de los fármacos , Colágeno/metabolismo , Humanos , Células Madre Mesenquimatosas/efectos de los fármacos , Células Madre Mesenquimatosas/metabolismo , Osteogénesis/fisiología , Ingeniería de Tejidos , Factor de Crecimiento Transformador beta1/metabolismo , Cicatrización de Heridas/efectos de los fármacosRESUMEN
The change in gingival tissue volume may be used to indicate changes in gingival inflammation, which may be useful for the clinical assessment of gingival health. Properly quantifying gingival tissue volume requires a robust technique for accurate registration and segmentation of longitudinally captured 3-dimensional (3D) images. In this paper, a semi-automated registration and segmentation method for micrometer resolution measurement of gingival-tissue volume is proposed for 3D optical coherence tomography (OCT) imaging. For quantification, relative changes in gingiva tissue volume are measured based on changes in the gingiva surface height using the tooth surface as a reference. This report conducted repeatability tests on this method drawn from repeated scans in one patient, indicating an error of the point cloud registration method for oral OCT imaging is 63.08 ± 4.52µm (1σ), and the measurement error of the gingival tissue average thickness is -3.40 ± 21.85µm (1σ).
RESUMEN
Thiol-epoxy "click" chemistry is employed for the first time to engineer a new cytocompatible PEG-based hydrogel system in aqueous media with the ability to encapsulate human mesenchymal stem cells (hMSCs) and control their fate for tissue regeneration. Cells were easily encapsulated into the hydrogels and exhibited high cell viability over 4 weeks of culture regardless of the presence of siRNA, complexed with polyethylenimine (PEI) in the form of siRNA/PEI nanocomplexes, indicating the biocompatibility of the developed hydrogel. Loading pro-osteogenic siNoggin in the hydrogel significantly enhanced the osteogenesis of encapsulated hMSCs, demonstrating the potential application of this system in tissue engineering.