RESUMO
Within the artery intima, endothelial cells respond to mechanical cues and changes in subendothelial matrix stiffness. Recently, we found that the aging subendothelial matrix stiffens heterogeneously and that stiffness heterogeneities are present on the scale of one cell length. However, the impacts of these complex mechanical micro-heterogeneities on endothelial cells have not been fully understood. Here, we simulate the effects of matrices that mimic young and aged vessels on single- and multi-cell endothelial cell models and examine the resulting cell basal strain profiles. Although there are limitations to the model which prohibit the prediction of intracellular strain distributions in alive cells, this model does introduce mechanical complexities to the subendothelial matrix material. More heterogeneous basal strain distributions are present in the single- and multi-cell models on the matrix mimicking an aged artery over those exhibited on the young artery. Overall, our data indicate that increased heterogeneous strain profiles in endothelial cells are displayed in silico when there is an increased presence of microscale arterial mechanical heterogeneities in the matrix.
Assuntos
Simulação por Computador , Células Endoteliais/citologia , Matriz Extracelular/metabolismo , Estresse Mecânico , Animais , Vasos Sanguíneos/fisiologia , Masculino , Camundongos Endogâmicos C57BL , Modelos BiológicosRESUMO
Synthetic hydrogels are important biomaterials for many biomedical applications and hydrogels produced via photo-gelation have shown particular promise. In this paper, we describe a new family of biodegradable hybrid hydrogels fabricated in aqueous solution via long wavelength UV photo-crosslinking using maleic chitosan and polyethylene glycol diacrylate (PEGDA) as precursors. The maleic chitosan precursor was prepared by a simple one-step chemical modification of chitosan, with high yields, and characterized by Fourier transform infrared spectroscopy, (1)H NMR and (13)C NMR. Maleic chitosan and PEGDA precursors at a wide range of weight feed ratios were mixed in aqueous solution and directly photo-crosslinked for 10 min under a long wavelength UV light (365 nm) using 4-(2-hydroxyethoxy) phenyl-(2-hydroxy-2-propyl) ketone (Irgacure 2959) as photoinitiator. It was observed that as the weight feed ratio of maleic chitosan to PEGDA decreased the pore sizes of the hydrogel samples decreased, thereby increasing the densities of the hydrogel networks and producing a lower swelling ratio and a higher compressive modulus. The molecular weight of PEGDA had a similar effect. Preliminary cell cytotoxicity tests of both the maleic chitosan precursor and maleic chitosan/PEGDA hydrogels, based on the MTT assay and live-dead assay, respectively, showed that these new chitosan-based biodegradable biomaterials were relatively non-toxic to bovine aortic endothelial cells at low dosages.