RESUMEN
Lesions involving the osteochondral unit are difficult to treat. Biomimetic scaffolds are previously shown as promising alternative. Such devices often lack multiple functional layers that mimic bone, cartilage, and the interface. In this study, multilayered scaffolds are developed based on the use of natural extracellular matrix (ECM)-like biopolymers. Particular attention is paid to obtain a complex matrix that mimics the native osteochondral transition. Porous, sponge-like chitosan-collagen-octacalcium phosphate (OCP) scaffolds are obtained. Collagen content increases while the amount of OCP particles decreases toward the cartilage layer. The scaffolds are bioactive as a mineral layer is deposited containing hydroxyapatite at the bony side. The scaffolds stimulate proliferation of human adipose-derived mesenchymal stem cells, but the degree of proliferation depends on the cell seeding density. The scaffolds give rise to a zone-specific gene expression. RUNX2, COL1A1, BGLAP, and SPP1 are upregulated in the bony layer of the scaffold. SOX9 is upregulated concomitant with COL2A1 expression in the cartilage zone. Mineralization in presence of the cells is prominent in the bone area with Ca and P steadily increasing over time. These results are encouraging for the fabrication of biomimetic scaffolds using ECM-like materials and featuring gradients that mimic native tissues and their interface.
Asunto(s)
Células Madre , Andamios del Tejido , Fosfatos de Calcio , Diferenciación Celular , Humanos , Porosidad , Ingeniería de TejidosRESUMEN
El objetivo principal de este trabajo es estudiar la cinética deliberación de cefalexina desde un biomaterial compuesto desarrollado recientemente, para demostrar que puede ser utilizado como un sistema de liberación controlada, durante periodos de tiempo prolongados. Además, se ajustaron diferentes modelos matemáticos a los perfiles de liberación obtenidos en cada formulación, con el propósito de determinar el mecanismo mediante el cual ocurre la liberación de cefalexina desde un sistema de liberación compuesto. Se demostró que el modelo propuesto por Peppas y Sahlin fue el que mejor ajuste presentó, ya que tiene en cuenta el fenómeno de difusión tipo Fickian y el fenómeno de relajación de las cadenas poliméricas. En todos los casos se descartó el efecto burst, por lo que se puede afirmar que casi todo el medicamento se encuentra ocluido dentro de las formulaciones y no en la superficie de éstas. Se pudo comprobar que la cefalexina es liberada mediante un fenómeno de difusión de tipo Fickian a través de los poros o canales formados en el sistema de liberación compuesto. Además, el fenómeno de relajación de las cadenas poliméricas no presenta una fuerte contribución a la liberación de cefalexina, pero su inclusión en la ecuación permite obtener un adecuado ajuste matemático (AU)
The main objective of this work is to study the kinetics of cefalexine release from a biomaterial compound developed recently, to show that it can be used as a controlled release system, for extended periods of time. Besides, different mathematical models were adjusted to the release profiles obtained in each formulation, with the purpose of determine the mechanism by which occurs the release of cefalexine from a composite release system. It was shown that the model proposed by Peppas and Sahlin was that the best fit presented, because, takes into account the phenomenon of Fickian diffusion and the phenomena of relaxation for polymeric chains. In all cases the effect burst was discarded, for what can affirm that almost all the medicine is occluded inside the formulations and not on the surface of these. It could be that the cefalexine is released through a phenomenon of Fickian diffusion through the pores or channels formed in the compound delivery system. Moreover, the phenomenon of relaxation for polymeric chains does not show a strong contribution to the release of cefalexine, but its inclusion in the equation, is necessary to obtain an appropriate mathematical adjustment (AU)