RESUMEN
Diabetes is a universal disease in the world. In the wounds of diabetic individuals, chronic inflammation and an inefficient fibrogenic process hinder the formation and deposition of the ECM, which delays the process of wound healing. To reconstruct the ECM of a diabetic patient's wound, in this work, we designed a pH-responsive "Double H-bonds" (hydrogen bond and hydrazone bond) hyaluronic acid-collagen hydrogel. This hydrogel can be self-gelled quickly in neutral and alkaline environments. But the weakly acidic inflammatory environment of diabetic wounds may accelerate the degradation of the hydrogel and the release of metformin. The in vitro results showed that the hydrogel can enhance the adhesion and infiltration of fibroblasts while inhibiting the growth of macrophages. Meanwhile, metformin could be released and polarize macrophages from M1 to M2, thereby accelerating the migration of fibroblasts and the production of collagen in a high glucose environment. The in vivo results proved that this hydrogel could remodel the ECM in diabetic mice wounds.
Asunto(s)
Diabetes Mellitus Experimental , Metformina , Animales , Diabetes Mellitus Experimental/tratamiento farmacológico , Ácido Hialurónico/farmacología , Hidrogeles/química , Hidrogeles/farmacología , Concentración de Iones de Hidrógeno , Inflamación/tratamiento farmacológico , RatonesRESUMEN
Due to their simple crystal structures, one-dimensional hydroxyapatite (HA) nanostructures are easily to be applied to understand the fundamental concepts about the influences of HA dimensionality on physical, chemical, and biological properties. So, in this work, three typical HA one-dimensional nanostructures, HA nanotubes, HA nanowires, and HA nanospheres, were prepared, whose theoretical structures were built also. in vitro cytocompatibility test proved that, contrasting with TCPS, HA one-dimensional nanostructures had certain degree of cytotoxicity because HA nanostructures increase the generation of intracellular reactive oxygen species (ROS) and intracellular calcium. Theoretical simulation indicated that HA nanosphere has higher intracellular ROS generation and lower ROS storage amount than HA nanowire and HA nanotube, which were the possible reasons for its stronger cytotoxicity. Among these typical one-dimensional nanostructures, owing to higher drug storage amount and sustained delivery ability, HA nanotube was more potential application in orthopedics. The tubular structure of HA nanotubes could be used as reservoirs for small molecule drugs or growth factors. The cytocompatibility of HA nanostructures can be improved obviously when they were produced into two-dimensional structures. The prepared multilayer structure can simulate lamellar structures of Harvard system and enhance the cytocompatibility of Ti substrate. Therefore, the method used in this work is a prospective method to improve the inherently bio-inert of Ti when used in hard tissue repairing.
Asunto(s)
Materiales Biocompatibles Revestidos/farmacología , Durapatita/química , Nanoestructuras/química , Animales , Animales Recién Nacidos , Calcio/metabolismo , Materiales Biocompatibles Revestidos/toxicidad , Sistemas de Liberación de Medicamentos , Liberación de Fármacos , Durapatita/farmacología , Durapatita/toxicidad , Ensayo de Materiales , Nanotubos/química , Nanocables/química , Osteoblastos/efectos de los fármacos , Osteoblastos/metabolismo , Ratas , Especies Reactivas de Oxígeno/metabolismo , Cráneo/citología , Espectroscopía Infrarroja por Transformada de Fourier , Vancomicina/administración & dosificaciónRESUMEN
After bone tumor resection, the large bony deficits are commonly reconstructed with Ti-based metallic endoprosthesis, which provide immediate stable fixation and allow early ambulation and weight bearing. However, when used in osteosarcoma resection, Ti implant-relative infection and tumor recurrence were recognized as the two critical factors for implantation failure. Hence, in this work, a novel zinc oxide nanoparticle decorating with naringin was prepared and immobilized onto Ti substrate. The drugs delivery profiles proved that in the bacterial infection and Warburg effect of osteosarcoma-induced acidic condition, naringin and Zn2+ can be released easily from the functional Ti substrate. The anti-osteosarcoma and antibacterial assay showed the delivered naringin and Zn2+ can induce a remarkable increase of oxidative stress in bacteria (Escherichia coli and Staphylococcus aureus) and osteosarcoma (Saos-2 cells) by producing reactive oxygen species (ROS). Accumulation of ROS results in damage of bacterial biofilm and bacterial membrane, leading to the leakage of bacterial RNA and DNA. Meanwhile, the increase of ROS induces osteosarcoma cell apoptosis by activating ROS/extracellular signal-regulated kinase signaling pathway. Furthermore, in vitro cellular experiments, including cell viability, alkaline phosphatase activity, collagen secretion, extracellular matrix mineralization level, indicated that the functional Ti substrate exhibited great potential for osteoblasts proliferation and differentiation. Hence, this study provides a simple and promising strategy of developing multifunctional Ti-based implants for the reconstruction of large bony after osteosarcoma resection.
Asunto(s)
Antineoplásicos/farmacología , Preparaciones de Acción Retardada/química , Flavanonas/farmacología , Osteosarcoma/terapia , Titanio/química , Óxido de Zinc/farmacología , Animales , Antibacterianos/administración & dosificación , Antibacterianos/farmacología , Antineoplásicos/administración & dosificación , Línea Celular Tumoral , Flavanonas/administración & dosificación , Humanos , Concentración de Iones de Hidrógeno , Nanopartículas/química , Osteogénesis/efectos de los fármacos , Ratas , Óxido de Zinc/administración & dosificaciónRESUMEN
Electronic skins (e-skins) with monitoring capabilities have attracted extensive attention and are being widely employed in wearable devices for medical diagnosis. In particular, e-skins based on strain sensors have been reported extensively due to their simple structure and efficient performance in collecting human physiological information. Flexible sensors with high sensitivity, simplified fabrication, and low-cost are highly desired for human signal monitoring; this work provides a novel strain-sensing e-skin with micro-structures, which is simply made of modified polydimethylsiloxane (PDMS) and silver nanowires (AgNWs). The fabricated e-skin has great sensitivity towards strain changes, and its mechanical properties and sensitivity could be regulated by varying the micro-structures. Furthermore, the e-skin demonstrated significant capacity for monitoring human body movements, temperature changes, and spatial resolution, highlighting its great potential in personalized medicine.