Publications

Doping of calcium phosphates (CaPs) with bioinorganic ions is a widely used strategy to enhance their biological performance in bone regeneration. However, conventional methods for ionic incorporation in CaP scaffolds often require high-temperature treatments or involve multiple complex steps. Here, we present two simple strategies to dope 3D-printed CaP scaffolds via incorporation of ions into the apatitic phase during the hydrolysis of alpha-tricalcium phosphate (alpha-TCP) to calcium deficient hydroxyapatite (CDHA). In the first strategy, ions were incorporated directly into the printing ink, whereas in the second, undoped robocasted scaffolds were immersed in ionic solutions, allowing ion incorporation into precipitated CDHA during phase transformation. We investigated several ions, including strontium (Sr2+), magnesium (Mg2+), silicon (SiO44- ) and gallium (Ga3+). Sr2+ and Ga3+ were successfully incorporated into the scaffolds, either by direct ink doping (Sr2+) or by soaking in ionic solutions (Sr2+ and Ga3+). Direct incorporation of Sr2+ in the ink resulted in a higher ion loading and release, enhancing bone formation and bone quality, as evidenced by increased mineral-to-matrix ratio and Young's modulus, as well as osteoinductive properties relative to non-doped scaffolds. Furthermore, we demonstrated for the first time the osteoinductive capacity of Ga3+ in an ectopic in vivo model.

JTD Keywords: 3d printing, Apatite, Biomimetic hydroxyapatite, Bone regeneration, Calcium phosphates, Calcium-phosphate cement, Differentiation, Ion doping, Magnesium-deficiency, Microporosity, Nanocrystals, Osteoinduction, Scaffold, Silicon, Substituted hydroxyapatite, Vitro

The fabrication of porous biophotonic scaffold using a robocasting is reported here. Such material could be used for in-situ activation of photoswitchable drugs, which is essential for improving therapeutic efficacy while minimizing side effects. The scaffold is made of a phosphate glass mixed with CaWO4:Yb3 +,Tm3 + crystals and SrAl2O4:Eu2+,Dy3 + phosphors. Upon 980 nm irradiation, the scaffold emits blue light and green afterglow, enabling in-situ activation post-implantation as NIR light penetrates tissue. The challenges related to the sintering process and its effect on the spectroscopic properties of the scaffold are discussed. The as-3D printed scaffold successfully enables one to activate the muscarinic photoswitchable drug Phthal Azobenzene Iperoxo (PAI) upon NIR excitation, confirming the potential for in-situ phototriggered delivery of drug action using tissue-permeable light stimulus.

JTD Keywords: Artificial skin, Bioactive glass, Cawo4 upconverter crystals, Design, Er3+, Nanocrystals, Persistent luminescence, Photoswitchable molecule, Scaffold, Surface, Up-conversion

Quantum dots (QDs) are semiconductor nanoparticles with unique optical and electronic properties, whose interest as potential nano-theranostic platforms for imaging and sensing is increasing. The design and use of QDs requires the understanding of cell-nanoparticle interactions at a microscopic and nanoscale level. Model systems such as supported lipid bilayers (SLBs) are useful, less complex platforms mimicking physico-chemical properties of cell membranes. In this work, we investigated the effect of topographical homogeneity of SLBs bearing different surface charge in the adsorption of hydrophilic QDs. Using quartz-crystal microbalance, a label-free surface sensitive technique, we show significant differences in the interactions of QDs onto homogeneous and inhomogeneous SLBs formed following different strategies. Within short time scales, QDs adsorb onto topographically homogeneous, defect-free SLBs is driven by electrostatic interactions, leading to no layer disruption. After prolonged QD exposure, the nanomechanical stability of the SLB decreases suggesting nanoparticle insertion. In the case of inhomogeneous, defect containing layers, QDs target preferentially membrane defects, driven by a subtle interplay of electrostatic and entropic effects, inducing local vesicle rupture and QD insertion at membrane edges. © 2021

JTD Keywords: adsorption, atomic force microscopy, bilayer formation, gold nanoparticles, hydrophilic quantum dots, lipid membrane defects, model, nanomechanics, quartz crystal microbalance with dissipation, size, supported lipid bilayers, surfaces, Atomic force microscopy, Atomic-force-microscopy, Cell membrane, Cytology, Defect-free, Electronic properties, Electrostatics, Hydrophilic quantum dot, Hydrophilic quantum dots, Hydrophilicity, Hydrophilics, Hydrophobic and hydrophilic interactions, Lipid bilayers, Lipid membrane defect, Lipid membrane defects, Lipid membranes, Lipids, Nanocrystals, Nanomechanics, Optical and electronic properties, Quantum dots, Quartz, Quartz crystal microbalance techniques, Quartz crystal microbalance with dissipation, Quartz crystal microbalances, Quartz-crystal microbalance, Semiconductor nanoparticles, Semiconductor quantum dots, Supported lipid bilayers

Abstract The development of nanostructured plasmonic biosensors has been widely widespread in the last years, motivated by the potential benefits they can offer in integration, miniaturization, multiplexing opportunities, and enhanced performance label-free biodetection in a wide field of applications. Between them, engineering tissues represent a novel, challenging, and prolific application field for nanostructured plasmonic biosensors considering the previously described benefits and the low levels of secreted biomarkers (?pM–nM) to detect. Here, we present an integrated plasmonic nanocrystals-based biosensor using high throughput nanostructured polycarbonate substrates. Metallic film thickness and incident angle of light for reflectance measurements were optimized to enhance the detection of antibody–antigen biorecognition events using numerical simulations. We achieved an enhancement in biodetection up to 3× as the incident angle of light decreases, which can be related to shorter evanescent decay lengths. We achieved a high reproducibility between channels with a coefficient of variation below 2% in bulk refractive index measurements, demonstrating a high potential for multiplexed sensing. Finally, biosensing potential was demonstrated by the direct and label-free detection of interleukin-6 biomarker in undiluted cell culture media supernatants from bioengineered 3D skeletal muscle tissues stimulated with different concentrations of endotoxins achieving a limit of detection (LOD) of ? 0.03 ng/mL (1.4 pM).

JTD Keywords: assay, crystals, drug, label-free biosensing, molecules, plasmonic nanostructures, sensors, skeletal muscle, tissue engineering, Biodetection, Biomarkers, Biosensors, Cell culture, Cells, Chemical detection, Histology, Interleukin-6, Interleukin6 (il6), Label free, Label-free biosensing, Muscle, Nano-structured, Nanocrystals, Plasmonic nanocrystals, Plasmonic nanostructures, Plasmonics, Polycarbonate substrates, Polycarbonates, Refractive index, Sensitivity, Skeletal muscle, Tissue engineering, Tissues engineerings