RESUMEN
Here we developed a semi-interpenetrating network (IPN) hydrogel obtained by free radical polymerization to fabricate a coated stent with the aim of incorporating a natural topography present in the human body to improve biological activity. The method involves sandwiching a bare metal stent in the semi-IPN hydrogel via solution cast molding. The bio-functionality of the membrane could be tuned by incorporating Polydopamine into the matrix, and also the mechanical property was optimized by choosing an adequate concentration of acrylamide. The coating containing polydopamine hydrogel showed good mechanical stability under continuous flow condition, as demonstrated by crimping and deployment into a catheter without damage. Stent polymer bonding was enhanced via polydopamine incorporation in the matrix. The non-thrombogenicity of the coating containing hydrogel was confirmed through dynamic hemocompatibility studies in vitro. Vascular simulations, including other biomechanical performance, like durability testing, radial strength, and recoil, were demonstrated. The dopamine containing hydrogel membrane (DCHM) was found to promote cell material interaction due to the ability of the catechol to bind protein and induce HUVECs cytoplasmic spreading, proliferation, and migration, with reduced smooth muscle cell (SMCs) activity. SMCs inhibition correlated well with the amount of incorporated catechol in the matrix. Our results show that this material used as coated stent could be more effective in suppressing platelet aggregation with improved haemocompatibility/biocompatibility for faster re-endothelialization than bare metal stent (BMS).
Asunto(s)
Materiales Biocompatibles Revestidos/farmacología , Hidrogeles/farmacología , Polímeros/farmacología , Stents , Trombosis/patología , Adsorción , Arterias/fisiología , Materiales Biomiméticos/química , Pruebas de Coagulación Sanguínea , Adhesión Celular/efectos de los fármacos , Movimiento Celular/efectos de los fármacos , Supervivencia Celular/efectos de los fármacos , Simulación por Computador , Análisis de Elementos Finitos , Hemodinámica/efectos de los fármacos , Hemólisis/efectos de los fármacos , Células Endoteliales de la Vena Umbilical Humana/citología , Células Endoteliales de la Vena Umbilical Humana/efectos de los fármacos , Células Endoteliales de la Vena Umbilical Humana/metabolismo , Humanos , Indoles/farmacología , Miocitos del Músculo Liso/citología , Miocitos del Músculo Liso/efectos de los fármacos , Adhesividad Plaquetaria/efectos de los fármacos , Resistencia a la TracciónRESUMEN
In order to meet the unmet medical needs for effective cancer treatment, multifunctional nanocarriers based on iron oxide nanoparticles hold tremendous promise. Here we report a superparamagnetic iron oxide nanoparticles based hexa-functional nanosystem for synergistic cancer theranostic applications by offering active tumour targeting, accumulation and complementary imaging capability by combining magnetic resonance imaging as well as near-infrared fluorescence, magnetophotothermia and chemotherapy. The uniquely designed nanosystem exhibited a paramount increase in the antitumour efficacy through the simultaneous application of multiple thermal effects called magnetophotothermia, which outweighed the therapeutic efficacy of the current thermo-chemo therapies or stand-alone therapies. The active tumour-seeking property with prolonged tumour accumulation and complementary imaging capability with improved sensitivity and resolution also augments the therapeutic efficacy of the proposed nanosystem. Additionally, the work proposes a deep-learning-based tumour cell nuclei detection technique from H&E stained images in anticipation of providing much inspiration for the future of precision histology.
Asunto(s)
Nanopartículas de Magnetita/química , Nanomedicina Teranóstica , Animales , Materiales Biocompatibles/química , Materiales Biocompatibles/farmacología , Línea Celular Tumoral , Supervivencia Celular/efectos de los fármacos , Quitosano/química , Portadores de Fármacos/química , Portadores de Fármacos/metabolismo , Humanos , Imagen por Resonancia Magnética , Masculino , Ratones , Ratones Endogámicos BALB C , Ratones Desnudos , Células 3T3 NIH , Neoplasias/diagnóstico por imagen , Neoplasias/tratamiento farmacológico , Neoplasias/patología , Paclitaxel/administración & dosificación , Paclitaxel/química , Trasplante HeterólogoRESUMEN
We prepared Janus microspheres based on sodium alginate for the encapsulation of mesenchymal stem cells (MSC) in one compartment and iron oxide nanoparticles (IONP) or a drug in the second compartment. 4% percent sodium alginate solution was allowed to pass through a septum-theta capillary device and react with 2.5% calcium chloride to allow crosslinking to occur in the solution, forming calcium alginate Janus microspheres. Physico-chemical characterization of microspheres was done by FTIR, TGA, and XRD after loading of stem cells and IONP/drug. The mechanical integrity of microspheres was tested at different time points, which showed that 4% alginate microspheres were mechanically stable for a long period of time. Live/dead staining of MSCs alone and the MTS assay of MSCs and DMSO co-loaded were performed, which showed less toxicity to MSC in the Janus configuration. IONP/MSC-loaded Janus microspheres were tested by magnetic manipulation for targeted MSC delivery for cartilage repair using an electromagnetic manipulation (EMM) device. Janus microspheres can be used for targeted stem cell/drug delivery using EMM for cartilage repair in the near future.