Considering increasing number of pathogens resistant towards commonly used antibiotics as well as antiseptics, there is a pressing need for antimicrobial approaches that are capable of inactivating pathogens efficiently without the risk of inducing resistances. In this regard, an alternative approach is the antimicrobial photodynamic therapy (aPDT). The antimicrobial effect of aPDT is based on the principle that visible light activates a per se non-toxic molecule, the so-called photosensitizer (PS), resulting in generation of reactive oxygen species that kill bacteria unselectively via an oxidative burst. During the last 10-20 years, there has been extensive in vitro research on novel PS as well as light sources, which is now to be translated into clinics. In this review, we aim to provide an overview about the history of aPDT, its fundamental photochemical and photophysical mechanisms as well as photosensitizers and light sources that are currently applied for aPDT in vitro. Furthermore, the potential of resistances towards aPDT is extensively discussed and implications for proper comparison of in vitro studies regarding aPDT as well as for potential application fields in clinical practice are given. Overall, this review shall provide an outlook on future research directions needed for successful translation of promising in vitro results in aPDT towards clinical practice.
Since the oral mucosa is continuously exposed to abundant microbes, one of its most important defense features is a highly proliferative, thick, stratified epithelium. The cellular mechanisms responsible for this are still unknown. The aim of this study was to determine whether multi-species oral biofilm contribute to the extensive stratification and primed antimicrobial defense in epithelium. Two in vitro models were used: 3D reconstructed human gingiva (RHG) and oral bacteria representative of multi-species commensal biofilm. The organotypic RHG consists of a reconstructed stratified gingiva epithelium on a gingiva fibroblast populated hydrogel (lamina propria). Biofilm was cultured from healthy human saliva, and consists of typical commensal genera Granulicatella and major oral microbiota genera Veillonella and Streptococcus. Biofilm was applied topically to RHG and host–microbiome interactions were studied over 7 days. Compared to unexposed RHG, biofilm exposed RHG showed increased epithelial thickness, more organized stratification and increased keratinocyte proliferation. Furthermore biofilm exposure increased production of RHG anti-microbial proteins Elafin, HBD2 and HBD3 but not HBD1, adrenomedullin or cathelicidin LL-37. Inflammatory and antimicrobial cytokine secretion (IL-6, CXCL8, CXCL1, CCL20) showed an immediate and sustained increase. In conclusion, exposure of RHG to commensal oral biofilm actively contributes to RHG epithelial barrier function.
We have introduced a novel class of higher-order spatial optical Ince-Gaussian solitons (IGSs) that constitute the third complete family of exact and orthogonal soliton solutions of the Snyder-Mitchell model. The transverse structure of the IGSs is characterized by the Ince polynomials and has an inherent elliptical symmetry. The IGSs form the exact and continuous transition modes between Hermite-Gaussian solitons and Laguerre-Gaussian solitons.
Local drug delivery systems have recently been developed for multiple diseases that have the requirements of site‐specific actions, prolonged delivery periods, and decreased drug dosage to reduce undesirable side effects. The challenge for such systems is to achieve directional and precise delivery in inaccessible narrow lesions, such as periodontal pockets or root canals in deeper portions of the dentinal tubules. The primary strategy to tackle this challenge is fabricating a smart tracking delivery system. Here, drug‐loaded biodegradable micromotors showing self‐propelled directional movement along a hydrogen peroxide concentration gradient produced by phorbol esters‐stimulated macrophages are reported. The drug‐loaded poly(lactic‐co‐glycolic acid) micromotors with asymmetric coverage of enzyme (patch‐like enzyme distribution) are prepared by electrospraying and postfunctionalized with catalase via 1‐ethyl‐3‐(3‐dimethylaminopropyl) carbodiimide coupling. Doxycycline, a common drug for the treatment of periodontal disease, is selected as a model drug, and the release study by high‐performance liquid chromatography is shown that both the postfunctionalization step and the presence of hydrogen peroxide have no negative influence on drug release profiles. The movement behavior in the presence of hydrogen peroxide is confirmed by nanoparticle tracking analysis. An in vitro model is designed and confirmed the response efficiency and directional control of the micromotors toward phorbol esters‐stimulated macrophages.
Starting from the vector angular spectrum of the electromagnetic beam, the analytical vectorial structure of the radially polarized beams (RPBs) is presented. The energy flux distributions of the RPBs are demonstrated. The physical pictures of the RPBs are well illustrated from the vectorial structure. This particular electromagnetic field is entirely transverse magnetic, and on axis it only has a longitudinal (z) electric-field component (i.e., no transverse electric field and no magnetic field at all on axis).
In this work, we provided a novel strategy of antibody-free biomarker analysis by in-situ synthesized molecularly imprinted polymers (MIPs) on movable valve microfluidic paper-based electrochemical device (Bio-MIP-ePADs) for clinical detection of biomarkers. The newly movable valves on the device enable continuous and convenient delivery of fluid, which guarantee the performance for fabricating MIPs structure during long time electropolymerization. Moreover, this strategy can directly detect antigens by taking advantage of molecular imprinting on paper-based device, which greatly decreases the cost during clinical testing, reduces the tedious washing procedure and does not need to consider the preservation of the antibody in enzyme linked immunosorbent assay (ELISA). This feature makes the chip suitable for the on-site family treatment or commercial products. To further validate the applicability of this proposed method for clinical diagnostic testing, carcinoembryonic antigen (CEA) was applied as prototyping model target for the clinical analysis. The proposed Bio-MIP-ePADs were cheap, easy to prepare, disposable and provided reliable analysis by comparing with ELISA. We hope the application of this technology will open up a new avenue to the point-of-care testing (POCT).
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