RESUMEN
Implants decorated with antimicrobial peptides (AMPs) can prevent infection and reduce the risk of creating antibiotic resistance. Yet the restricted mobility of surficial AMP often compromises its activity. Here, we report a simple but effective strategy to allow a more flexible display of AMP on the biomaterial surface and demonstrate its efficacy for wound healing. The AMP, tachyplesin I (Tac), is tagged with the polyhydroxyalkanoate-granule-associated protein (PhaP) and immobilized on haloarchaea-produced poly(3-hydroxybutyrate-co-3-hydroxyvalerate) (PHBHV) via hydrophobic interaction. The PhaP-Tac coating effectively inhibits the growth of both Gram-negative and Gram-positive bacteria. It also increases the surface hydrophilicity to improve fibroblast proliferation in vitro, and accelerates wound healing by decreasing bacterial counts to below 105â¯CFU per gram of tissue in a deep-wound mouse model in vivo. Taken together, these findings demonstrate an effective strategy to realize the full potential of AMPs in imparting implants with an anti-microbial activity that is localized and potent.
Asunto(s)
Antiinfecciosos/farmacología , Péptidos Catiónicos Antimicrobianos/farmacología , Materiales Biocompatibles/farmacología , Proteínas de Unión al ADN/farmacología , Péptidos Cíclicos/farmacología , Animales , Bacterias/efectos de los fármacos , Proteínas Bacterianas/farmacología , Muerte Celular/efectos de los fármacos , Línea Celular , Materiales Biocompatibles Revestidos/farmacología , Humanos , Interacciones Hidrofóbicas e Hidrofílicas , Masculino , Ratones , Pruebas de Sensibilidad Microbiana , Poliésteres/química , Poliésteres/metabolismo , Ingeniería de Proteínas , Ratas , Proteínas Recombinantes de Fusión/farmacología , Propiedades de Superficie , Cicatrización de Heridas/efectos de los fármacosRESUMEN
This study was to investigate the differences of inflammatory reaction and oxidative stress due to sulfur mustard (SM)-induced acute pulmonary injury via two ways in rats. In intraperitoneal and tracheal SM groups, injected intraperitoneally and instilled intratracheally with 0.1mL diluted SM (0.96 LD50=8mg/kg) and SM (0.98 LD50=2mg/kg) were administered in rats. In bronchoalveolar lavage fluid, serum, and alveolar septum, lactate dehydrogenase, glutathione peroxidase, tumor necrosis factor-α, interleukin-1ß, interleukin-6, C-reactive protein, intercellular adhesion molecule-1, vascular cell adhesion molecule-1, l-selectin, r-glutamyl transpeptidase, thiobarbituric acid reactive substances levels as well as the expression of CD4, CD20, CD68, 8-hydroxy deoxyguanosine, nuclear factor-E2-related factor 2, and heme oxygenase-1 measured by ELISA, immune scatter turbidimetry and immunohistochemical method in the intraperitoneal SM group were increased at each time-point compared with the tracheal SM groups, respectively. These data demonstrated an increased inflammatory reaction and oxidative stress indices in rat via intraperitoneal injection under similar SM LD50 doses.