RESUMO
Emerging regenerative cell therapies for alveolar bone loss have begun to explore the use of cell laden hydrogels for minimally invasive surgery to treat small and spatially complex maxilla-oral defects. However, the oral cavity presents a unique and challenging environment for in vivo bone tissue engineering, exhibiting both hard and soft periodontal tissue as well as acting as key biocenosis for many distinct microbial communities that interact with both the external environment and internal body systems, which will impact on cell fate and subsequent treatment efficacy. Herein, we design and bioprint a facile 3D in vitro model of a human dentine interface to probe the effect of the dentine surface on human mesenchymal stem cells (hMSCs) encapsulated in a microporous hydrogel bioink. We demonstrate that the dentine substrate induces osteogenic differentiation of encapsulated hMSCs, and that both dentine and ß-tricalcium phosphate substrates stimulate extracellular matrix production and maturation at the gel-media interface, which is distal to the gel-substrate interface. Our findings demonstrate the potential for long-range effects on stem cells by mineralized surfaces during bone tissue engineering and provide a framework for the rapid development of 3D dentine-bone interface models.
Assuntos
Diferenciação Celular , Dentina , Células-Tronco Mesenquimais , Osteogênese , Engenharia Tecidual , Humanos , Osteogênese/fisiologia , Engenharia Tecidual/métodos , Fosfatos de Cálcio , Hidrogéis , Técnicas In Vitro , Bioimpressão , Alicerces Teciduais , Propriedades de Superfície , Matriz Extracelular , Células CultivadasRESUMO
AIM: Develop modified dextran nanoparticles showing potential to assist with drug permeation across the blood-brain barrier for the delivery of neuropeptides. METHODS: Nanoparticles loaded by emulsification with model macromolecular actives were characterized in terms of stability, cytotoxicity and drug-release behavior. Peptide-loaded nanoformulations were tested in an in vivo trout model and in food-deprived mice. RESULTS: Nanoformulations loaded with model peptides showed good stability and appeared nontoxic in low concentration against human brain endothelial cells. They were found to preserve the bioactivity of loaded peptides (angiotensin II) as demonstrated in vivo using a trout model, and to induce a transient reduction of food consumption in mice when loaded with an anorexigenic octaneuropeptide. CONCLUSION: Octylglyceryl dextran-graft-poly(lactic acid) nanoparticles formulated by emulsification demonstrate potential for peptide delivery.
