RESUMEN
Dynamic biomaterials excel at recapitulating the reversible interlocking and remoldable structure of the extracellular matrix (ECM), particularly in manipulating cell behaviors and adapting to tissue morphogenesis. While strategies based on dynamic chemistries have been extensively studied for ECM-mimicking dynamic biomaterials, biocompatible molecular means with biogenicity are still rare. Here, we report a nature-derived strategy for fabrication of dynamic biointerface as well as a three-dimensional (3D) hydrogel structure based on reversible receptor-ligand interaction between the glycopeptide antibiotic vancomycin and dipeptide d-Ala-d-Ala. We demonstrate the reversible regulation of multiple cell types with the dynamic biointerface and successfully implement the dynamic hydrogel as a functional antibacterial 3D scaffold to treat tissue repair. In view of the biogenicity and high applicability, this nature-derived reversible molecular strategy will bring opportunities for malleable biomaterial design with great potential in biomedicine.
Asunto(s)
Matriz Extracelular/química , Matriz Extracelular/fisiología , Ingeniería de Proteínas/métodos , Alanina/química , Alanina/metabolismo , Materiales Biocompatibles/química , Biomimética/métodos , Dipéptidos/metabolismo , Humanos , Hidrogeles/química , Ligandos , Vancomicina/química , Vancomicina/metabolismoRESUMEN
PURPOSE: To clarify sotalol's classification in the BCS versus BDDCS systems through cellular, rat everted sac and PAMPA permeability studies. METHODS: Studies were carried out in Madin Darby canine kidney (MDCK) and MDR1-transfected MDCK (MDCK-MDR1) cell lines, rat everted gut sacs and the Parallel Artificial Membrane Permeability Assay (PAMPA) system. Three-hour transport studies were conducted in MDCK cell lines (with apical pH changes) and MDCK-MDR1 cells (with and without the P-glycoprotein inhibitor GG918); male Sprague-Dawley rats (300~350 g) were used to prepare everted sacs. In the PAMPA studies, drug solutions at different pH's were dosed in each well and incubated for 5 h. Samples were measured by LC-MS/MS, or liquid scintillation counting and apparent permeability (P(app)) was calculated. RESULTS: Sotalol showed low permeability in all of the cultured-cell lines, everted sacs and PAMPA systems. It might be a border line P-glycoprotein substrate. The PAMPA study showed that sotalol's permeability increased with a higher apical pH, while much less change was found in MDCK cells. CONCLUSION: The low permeability rate for sotalol correlates with its Class 3 BDDCS assignment and lack of in vivo metabolism.
Asunto(s)
Antagonistas Adrenérgicos beta/farmacocinética , Antiarrítmicos/farmacocinética , Absorción Intestinal , Mucosa Intestinal/metabolismo , Sotalol/farmacocinética , Subfamilia B de Transportador de Casetes de Unión a ATP/antagonistas & inhibidores , Antagonistas Adrenérgicos beta/metabolismo , Animales , Antiarrítmicos/metabolismo , Línea Celular , Permeabilidad de la Membrana Celular , Perros , Intestinos/citología , Masculino , Membranas Artificiales , Ratas , Ratas Sprague-Dawley , Sotalol/metabolismoRESUMEN
Antibacterial coatings that inhibit bacterial adhesion are essential for many implanted medical devices. A variety of antibacterial strategies, such as repelling or killing bacteria, have been developed, but not yet been completely successful. Here, we develop a universal biocompatible coating for enhanced lubrication and bacterial inhibition. The coating is designed based on mussel-inspired surface-attachable dopamine bases and consists of lubricating zwitterionic polymers poly(2-methacryloxyethyl phosphorylcholine) (MPC) and a bacterial membrane destroying anti-bacteria molecule poly(3-hydroxybutyric acid) (PHB). The coating boasts strong adhesion to surfaces of various materials (such as polydimethylsiloxane (PDMS)/ceramic/316L stainless steel (316L SS); it is biocompatible, and cell/platelet/bacteria repelling, significantly inhibiting bacterial growth. We envision that our strategy represents a universal strategy for surface functionalization of a variety of biomedical devices and implants.