Biomimicry strategies, inspired from natural organization of living organisms, are being widely used in the design of nanobiomaterials. Particularly, nonlithographic techniques have shown immense potential in the facile fabrication of nanostructured surfaces at large-scale production. Orthopedic biomaterials or coatings possessing extracellular matrix-like nanoscale features induce desirable interactions between the bone tissue and implant surface, also known as osseointegration. In this study, nanopillared chitosan/gelatin (C/G) films were fabricated using nanoporous anodic alumina molds, and their antibacterial properties as well as osteogenesis potential were analyzed by comparing to the flat C/G films and tissue culture polystyrene as controls. In vitro analysis of the expression of RUNX2, osteopontion, and osteocalcin genes for mesenchymal stem cells as well as osteoblast-like Saos-2 cells was found to be increased for the cells grown on nano C/G films, indicating early-stage osteogenic differentiation. Moreover, the mineralization tests (quantitative calcium analysis and alizarin red staining) showed that nanotopography significantly enhanced the mineralization capacity of both cell lines. This work may provide a new perspective of biomimetic surface topography fabrication for orthopedic implant coatings with superior osteogenic differentiation capacity and fast bone regeneration potential.
Injectable, self-healable, and pH-responsive hybrid hydrogels are highly promising biomaterials for controlled and long-term therapeutic agent release in cancer treatment. Herein, we fabricated an injectable, self-healable, and pH-responsive hybrid hydrogel through the formation of the hydrazone bond between hydrazide-functionalized gelatin (Gel-ADH) and aldehyde-functionalized PEG (diBA-PEG) polymers. During gelation, the resulting pregels were also integrated with laponite (LAP) nanodisks loaded with an anticancer drug, doxorubicin (DOX), yielding to hybrid Gel-ADH/diBA-PEG/LAP@DOX hydrogels. The gelation time of the hybrid hydrogel was observed to be 80 s and the resulting hybrid hydrogels demonstrated excellent injectability and rapid self-healing capability. The gel−sol transition behaviors of hybrid hydrogels indicated an outstanding gelation stability, which is a highly desirable feature in controlled drug delivery application. The injectable hybrid Gel-ADH/diBA-PEG/LAP@DOX hydrogels exhibited a very efficient pHdependent long-term drug release profile. Biocompatibility of the hydrogel components (Gel-ADH, diBA-PEG, and LAP) was also tested using the human breast cell line (SVCT) and endothelial cell line (HUVEC). All components of the hybrid hydrogel possess excellent biocompatibility and even support cell proliferation. Moreover, the cytotoxicity of the hydrogels was investigated on the human breast cancer cell line (MCF-7) and triple-negative breast cancer cell line (MDA-MB-231). Our results clearly suggested that this injectable, self-healable, and pH-responsive hybrid Gel-ADH/diBA-PEG/LAP@DOX hydrogel offers a promising potential as a drug carrier for long-term and controlled release application.
Alzheimer disease (AD) is a major cause of death in the world, and despite intense efforts, there is still no cure for this neurodegenerative disorder. Therefore, early diagnosis of AD is of prime importance, and extensive studies are being conducted to improve the current early detection capabilities and to identify new potential biomarkers for this disease. Here in, we report the fabrication of a novel nanobiosensor platform for the surface‐enhanced Raman spectroscopy (SERS)‐based ultrasentisitive detection of beta‐amyloid (1–42) peptide (Aβ[1–42]), a well‐established biomarker of AD. Polymeric films having multibranched nanopillared surfaces (MNS) were first fabricated by drop‐casting polycarbonate solutions onto anodized aluminum oxide molds that possess hierarchically branched pores. After peeling from the nanoporous molds, a 20‐nm Au coating allowed these MNS substrates to sense sub‐picomolar levels of Thioflavin‐T (ThT), a SERS‐active dye, clinically used to diagnose amyloid plaque presence. Of particular interest, the ThT‐modified MNS films demonstrated a gradual ThT SERS signal suppression when incubated with increasing concentrations of Aβ(1–42), and this trend was used to obtain a limit of detection value of 0.5 pg/ml and a linear dynamic range between 0.5 pg/ml and 100 ng/ml. The developed biosensor platform has stable ThT SERS signals for extended periods and displayed promising results in artificial saliva. Ongoing studies are focused on its potential with real body fluids.
The melt-infiltration technique enables the fabrication of complex nanostructures for a wide range of applications in optics, electronics, biomaterials, and catalysis. Here, anemone-like nanostructures are produced for the first time under the surface/interface principles of melt-infiltration as a non-lithographic method. Functionalized anodized aluminum oxide (AAO) membranes are used as templates to provide large-area production of nanostructures, and polycarbonate (PC) films are used as active phase materials. In order to understand formation dynamics of anemone-like structures finite element method (FEM) simulations are performed and it is found that wetting behaviour of the polymer is responsible for the formation of cavities at the caps of the structures. These nanostructures are examined in the surface-enhanced-Raman-spectroscopy (SERS) experiment and they exhibit great potential in this field. Reproducible SERS signals are detected with relative standard deviations (RSDs) of 7.2-12.6% for about 10,000 individual spots. SERS measurements are demonstrated at low concentrations of Rhodamine 6G (R6G), even at the picomolar level, with an enhancement factor of ∼10(11). This high enhancement factor is ascribed to the significant electric field enhancement at the cavities of nanostructures and nanogaps between them, which is supported by finite difference time-domain (FDTD) simulations. These novel nanostructured films can be further optimized to be used in chemical and plasmonic sensors and as a single molecule SERS detection platform.
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