In the initial stages of dental plaque formation, early colonizing bacteria bind to receptor structures in the pellicle, a proteinaceous film formed instantly after cleaning of the tooth surface. Dental restorative materials with surface characteristics different from the tooth might affect pellicle formation and the ability of bacteria to colonize the oral cavity. in this study (i) roughness and chemical composition of glass ionomer and composite resin surfaces before and after polishing, and (ii) the adsorption of salivary proteins and bacterial adherence to the pellicle-coated surfaces were examined. Compared with unpolished composite resin, unpolished glass ionomer had higher surface roughness, contained more inorganic, positively charged components, collected more proteins, and promoted better bacterial adherence. Polishing had the most pronounced effect on the composite resin, giving an enlarged and a rougher surface with a more inorganic character. Polishing the composite resin also led to increased biofilm formation
Tumor cells interact with the microenvironment that specifically supports and promotes tumor development. Key components in the tumor environment have been linked to various aggressive cancer features and can further influence the presence of subpopulations of cancer cells with specific functions, including cancer stem cells and migratory cells. To model and further understand the influence of specific microenvironments we have developed an experimental platform using cell-free patient-derived scaffolds (PDSs) from primary breast cancers infiltrated with standardized breast cancer cell lines. This PDS culture system induced a series of orchestrated changes in differentiation, epithelial-mesenchymal transition, stemness and proliferation of the cancer cell population, where an increased cancer stem cell pool was confirmed using functional assays. Furthermore, global gene expression profiling showed that PDS cultures were similar to xenograft cultures. Mass spectrometry analyses of cell-free PDSs identified subgroups based on their protein composition that were linked to clinical properties, including tumor grade. Finally, we observed that an induction of epithelial-mesenchymal transition-related genes in cancer cells growing on the PDSs were significantly associated with clinical disease recurrences in breast cancer patients. Patient-derived scaffolds thus mimics in vivo-like growth conditions and uncovers unique information about the malignancy-inducing properties of tumor microenvironment. © 2019 The Authors
Titanium (Ti) is a well known metallic biomaterial extensively used in dental, orthopaedic-, and occasionally also in blood contacting applications. It integrates well to bone and soft tissues, and is shown upon blood plasma contact to activate the intrinsic pathway of coagulation and bind complement factor 3b. The material properties depend largely on those of the nm-thick dense layer of TiO2 that becomes rapidly formed upon contact with air and water. The spontaneously formed amorphous Ti-oxide has a pzc∼5-6 and its water solubility is at the order of 1-2 micromolar. It is often subjected to chemical- and heat treatments in order to increase the anatase- and rutile crystallinity, to modify the surface topography and to decrease the water solubility. In this work, we prepared sol-gel derived titanium and smooth PVD titanium surfaces, and analysed their oxide and protein deposition properties in human blood plasma before and after annealing at 100-500°C or upon UVO-treatment for up to 96hours. The blood plasma results show that complement deposition vanished irreversibly after heat treatment at 250-300°C for 30minutes or after UVO exposure for 24hours or longer. XPS and infrared spectroscopy indicated change of surface water/hydroxyl binding upon the heat- and UVO treatments, and increased Ti oxidation. XRD analysis confirmed an increased crystallinity and both control (untreated) and annealed smooth titanium displayed low XRD-signals indicating some nanocrystallinity, with predominantly anatase phase. The current results show that the behaviour of titanium dioxide in blood contact can be controlled through relatively simple means, such as mild heating and illumination in UV-light, which both likely irreversibly change the stoichiometry and structure of the outmost layers of titanium dioxide and its OH/H2O binding characteristics.
The introduction of vaccines is regarded as one of the most successful medical interventions to date. However, there is a clear need for the development of new vaccines for diseases which require the induction of a potent cellular immune response. Advancements in the field of vaccine research have resulted in a move away from the use of whole organisms and towards the use of subunit vaccines which consist of highly purified antigens with an improved safety profile. Adjuvants are immunostimulatory components that are included in subunit vaccine formulations to help direct and amplify adaptive immune responses. Chitosan is a cationic polysaccharide that has been examined in an adjuvant setting due to its biocompatible and biodegradable nature. The polysaccharide has been shown to have the capacity to induce Th1 cell responses following vaccination by injection or mucosal routes, supporting its application as an alternative to alum for vaccines that promote cell-mediated immunity. Here, we provide an overview of the physico-chemical properties of chitosan with a focus on the specific characteristics that dictate the type and scale of the immune responses induced. The potential to finely tailor chitosan polymers in order to direct specific types of immune responses can provide invaluable tools for the design of novel chitosan-based adjuvants and biomaterials.
Infection constitutes a major risk for implant failure, but the reasons why biomaterial sites are more vulnerable than normal tissue are not fully elucidated. In this study, a soft tissue infection model was developed, allowing the analysis of cellular and molecular responses in each of the sub-compartments of the implant-tissue interface (on the implant surface, in the surrounding exudate and in the tissue). Smooth and nanostructured titanium disks with or without noble metal chemistry (silver, gold, palladium), and sham sites, were inoculated with Staphylococcus epidermidis and analysed with respect to number of viable bacteria, number, viability and gene expression of host cells, and using different morphological techniques after 4 h, 24 h and 72 h. Non-infected rats were controls. Results showed a transient inflammatory response at control sites, whereas bacterial administration resulted in higher recruitment of inflammatory cells (mainly polymorphonuclear), higher, continuous cell death and higher gene expression of tumour necrosis factor-alpha, interleukin-6, interleukin-8, Toll-like receptor 2 and elastase. At all time points, S. epidermidis was predominantly located in the interface zone, extra- and intracellularly, and lower levels were detected on the implants compared with surrounding exudate. This model allows detailed analysis of early events in inflammation and infection associated to biomaterials in vivo leading to insights into host defence mechanisms in biomaterial-associated infections.
Chitosan is a cationic polysaccharide that has been evaluated as an adjuvant due to its biocompatible and biodegradable nature. The polysaccharide can enhance antibody responses and cell-mediated immunity following vaccination by injection or mucosal routes. However, the optimal polymer characteristics for activation of dendritic cells (DCs) and induction of antigen-specific cellular immune responses have not been resolved. Here, we demonstrate that only chitin-derived polymers with a high degree of deacetylation (DDA) enhance generation of mitochondrial reactive oxygen species (mtROS), leading to cGAS-STING mediated induction of type I IFN. Additionally, the capacity of the polymers to activate the NLRP3 inflammasome was strictly dependent on the degree and pattern of deacetylation and mtROS generation. Polymers with a DDA below 80% are poor adjuvants while a fully deacetylated polyglucosamine polymer is most effective as a vaccine adjuvant. Furthermore, this polyglucosamine polymer enhanced antigen-specific Th1 responses in a NLRP3 and STING-type I IFN-dependent manner. Overall these results indicate that the degree of chitin deacetylation, the acetylation pattern and its regulation of mitochondrial ROS are the key determinants of its immune enhancing effects. © 2021 The Author(s)