ABSTRACT
The development of synthetic bone graft substitutes is an intense area of research due to the complications associated with the harvest of autogenous bone and concerns about the supply of allogenic bone. Porous resorbable polymers have been used extensively in hard tissue engineering applications, but currently lack load-bearing capacity. Supercritical carbon dioxide (scCO(2)) processing is used as a novel method to simultaneously impart a porous structure and disperse a nano-clay in a resorbable polymer matrix suitable for load-bearing applications. Porous resorbable polylactic acid (PLA)/cloisite clay nanocomposite constructs prepared using scCO(2) processing exhibit a 2.5-fold increase in compressive strength compared with pure polymer constructs. The resulting mechanical properties are comparable with human cancellous and cortico-cancellous bone. In addition to the significant improvements in mechanical properties, the nanocomposite constructs display a biocompatibility greater than that of polystyrene culture plate controls. Furthermore, calcium phosphate-rich deposits could clearly be seen on the surface of the constructs, as well as at the center of the cultured constructs, indicating that osteoblasts are able to penetrate the porous network of the nanocomposite constructs. Cellular infiltration of these constructs is important for their in vivo use as bone graft substitutes. The diameter of the pores suggests that these constructs would also support neovascularization, which is integral for nutrient transport.
Subject(s)
Biocompatible Materials/chemistry , Bone Substitutes/chemistry , Carbon Dioxide/chemistry , Lactic Acid/chemistry , Polymers/chemistry , Compressive Strength , Humans , Nanocomposites , Osteoblasts/cytology , Polyesters , Porosity , Surface Properties , Tissue Engineering/methodsABSTRACT
Dendrimers have emerged as topical microbicides to treat vaginal infections. This study explores the in vitro, in vivo antimicrobial activity of PAMAM dendrimers, and the associated mechanism. Interestingly, topical cervical application of 500 microg of generation-4 neutral dendrimer (G(4)-PAMAM-OH) showed potential to treat the Escherichia coli induced ascending uterine infection in guinea pig model of chorioamnionitis. Amniotic fluid collected from different gestational sacs of infected guinea pigs posttreatment showed absence of E. coli growth in the cultures plated with it. The cytokine level [tumor necrosis factor (TNFalpha) and interleukin (IL-6 and IL-1beta)] in placenta of the G(4)-PAMAM-OH treated animals were comparable to those in healthy animals while these were notably high in infected animals. Since, antibacterial activity of amine-terminated PAMAM dendrimers is known, the activity of hydroxyl and carboxylic acid terminated PAMAM dendrimers was compared with it. Though the G(4)-PAMAM-NH(2) shows superior antibacterial activity, it was found to be cytotoxic to human cervical epithelial cell line above 10 microg/mL, while the G(4)-PAMAM-OH was non-cytotoxic up to 1mg/mL concentration. Cell integrity, outer (OM) and inner (IM) membrane permeabilization assays showed that G(4)-PAMAM-OH dendrimer efficiently changed the OM permeability, while G(4)-PAMAM-NH(2) and G(3.5)-PAMAM-COOH damaged both OM and IM causing the bacterial lysis. The possible antibacterial mechanism are G(4)-PAMAM-NH(2) acts as polycation binding to the polyanionic lipopolysaccharide in E. coli, the G(4)-PAMAM-OH forms hydrogen bonds with the hydrophilic O-antigens in E. coli membrane and the G(3.5)-PAMAM-COOH acts as a polyanion, chelating the divalent ions in outer cell membrane of E. coli. This is the first study which shows that G(4)-PAMAM-OH dendrimer acts as an antibacterial agent.
Subject(s)
Amniotic Fluid/microbiology , Anti-Bacterial Agents/pharmacology , Chorioamnionitis/drug therapy , Dendrimers/pharmacology , Escherichia coli Infections/drug therapy , Escherichia coli/drug effects , Animals , Anti-Bacterial Agents/metabolism , Anti-Bacterial Agents/toxicity , Cell Line , Cell Membrane/drug effects , Cell Membrane/ultrastructure , Cell Membrane Permeability/drug effects , Chemistry, Pharmaceutical , Chorioamnionitis/immunology , Chorioamnionitis/microbiology , Dendrimers/metabolism , Dendrimers/toxicity , Disease Models, Animal , Dose-Response Relationship, Drug , Escherichia coli/growth & development , Escherichia coli/metabolism , Escherichia coli/ultrastructure , Escherichia coli Infections/complications , Escherichia coli Infections/immunology , Female , Guinea Pigs , Humans , Interleukin-1beta/metabolism , Interleukin-6/metabolism , Mice , Microbial Viability/drug effects , Microglia/drug effects , Microscopy, Electron, Scanning , Nylons/pharmacology , O Antigens/metabolism , Placenta/drug effects , Placenta/immunology , Pregnancy , Time Factors , Tumor Necrosis Factor-alpha/metabolismABSTRACT
The effect of primary particle shape on the porosity, mechanical strength, and luminescence intensity of metal chalcogenide aerogels was probed by comparison of CdSe aerogels prepared from spherical and rod-shaped particles. Rod-shaped particles yield aerogels with polymeric morphologies in contrast to the colloidal morphology obtained from spherical particles. Relative to the colloidal analogues, the polymeric CdSe aerogels exhibit twice the surface area, a doubling of the complex viscosity for 5 wt % aerogel-PDMS composites, and a 25-fold increase in emission intensity. Altering the shape of the building block from which nanostructured networks are assembled is an effective way to tune the basic properties of metal chalcogenide semiconducting aerogels.
