This study evaluates the potential of niobium oxide-polydimethylsiloxane (PDMS) composites for tuning cellular response of fibroblasts, a key cell type of soft tissue/implant interfaces. In this study, various hybrid coatings of niobium oxide and PDMS with different niobium oxide concentrations were synthesized and characterized using scanning electron microscopy, X-ray photoelectron spectrometry (XPS), and contact angle goniometry. The coatings were then applied to 96-well plates, on which primary fibroblasts were seeded. Fibroblast viability, proliferation, and morphology were assessed after 1, 2, and 3 days of incubation using WST-1 and calcein AM assays along with fluorescent microscopy. The results showed that the prepared coatings had distinct surface features with submicron spherical composites covered in a polymeric layer. The water contact angle measurement demonstrated that the hybrid surfaces were much more hydrophobic than the original pure niobium oxide and PDMS. The combination of surface roughness and chemistry resulted in a biphasic cellular response with maximum fibroblast density on substrate with 40 wt % of niobium oxide. The results of the current study indicate that by adjusting the concentration of niobium oxide in the coating, a desirable cell response can be achieved to improve tissue/implant interfaces.
Lipid nanoparticles of internal cubic symmetry, termed cuboplexes, are potential nonviral delivery vehicles for gene therapy due to their "topologically active" nature, which may enhance endosomal escape and improve delivery outcomes. In this study, we have used cationic cuboplexes, based on monoolein (MO) doped with a cationic lipid, for the encapsulation and delivery of antisense green fluorescent protein (GFP)—small interfering RNA (siRNA) into Chinese Hamster Ovary (CHO)—GFP cells. Agarose gel electrophoresis has confirmed the successful encapsulation of siRNA within cationic cubosomes, while synchrotron small-angle X-ray scattering (SAXS) demonstrated that the underlying cubic nanostructure of the particles was retained following encapsulation. The cationic cubosomes were shown to be reasonably nontoxic against the CHO-GFP cell line. Fluorescence-activated cell sorting (FACS) provided evidence of the successful transfection to CHO-GFP cells. Knockdown efficiency was strongly linked to the type of cationic lipid used, although all cubosomes had essentially the same internal nanostructure. The gene knockdown efficiency for some cationic cubosomes was shown to be higher than lipofectamine, which is a commercially available liposome-based formulation, while the controlled release of the siRNA from the cubosomes over a 72 h period was observed using confocal microscopy. This combination exemplifies the potential of cationic cuboplexes as a novel, nonviral, controlled-release delivery vector for siRNA.
Owing to several key attributes, diamond is an attractive candidate material for neural interfacing electrodes. The emergence of additive-manufacturing (AM) of diamond-based materials has addressed multiple challenges associated with the fabrication of diamond electrodes using the conventional chemical vapor deposition (CVD) approach. Unlike the CVD approach, AM methods have enabled the deposition of three-dimensional diamond-based material at room temperature. This work demonstrates the feasibility of using laser metal deposition to fabricate diamond–titanium hybrid electrodes for neuronal interfacing. In addition to exhibiting a high electrochemical capacitance of 1.1 mF cm–2 and a low electrochemical impedance of 1 kΩ cm2 at 1 kHz in physiological saline, these electrodes exhibit a high degree of biocompatibility assessed in vitro using cortical neurons. Furthermore, surface characterization methods show the presence of an oxygen-rich mixed-phase diamond–titanium surface along the grain boundaries. Overall, we demonstrated that our unique approach facilitates printing biocompatible titanium–diamond site-specific coating-free conductive hybrid surfaces using AM, which paves the way to printing customized electrodes and interfacing implantable medical devices.
Abstract The blood‐brain barrier (BBB) poses a significant challenge in delivering therapeutic agents for brain diseases due to its high selectivity against foreign substances. This limitation greatly hampers the effectiveness of conventional chemotherapeutic drugs in treating brain cancers. In response, lipid‐based nanoparticles (LNPs) have emerged as a promising approach, offering opportunities for targeted drug delivery by conjugating targeting ligands onto their surface. This review provides a comprehensive overview of recent advancements in utilizing LNPs to traverse the BBB for enhanced transport of bioactive compounds into the brain, specifically for cancer treatments. Beginning with an exploration of the biological structure and functions of the BBB and the blood‐brain tumor barrier (BBTB), the review highlights the advantages presented by LNPs. Subsequently, it delves into strategies for surface modification of nanoparticles to enhance BBB targeting and improve efficacy in brain cancer treatment. Finally, the review offers insights into future prospects for designing the next generation of LNPs. The review presented herein aims to contribute to the ongoing efforts in overcoming the challenges associated with BBB penetration, ultimately advancing therapeutic strategies for brain cancer and other neurological disorders.
Lipid nanoparticles (LNP) have been widely used as carriers for drugs and genes, including in mRNA-vaccines for COVD-19. A special class of LNP, lyotropic liquid crystalline LNP, comprise mainly of amphiphilic lipids self-assembling into two- and three-dimensional, inverse hexagonal, and cubic nanostructures (Fig. 1). Mesophase structures of self-assembled lyotropic liquid crystalline nanoparticles are important factors that directly influence their ability to encapsulate and release drugs and their biological activities. 1, 2 For example, the release rate of hydrophilic compounds was found to be much faster in the cubic phase than in the hexagonal phase, micellar cubic phase, and microemulsion. 3 Additionally, it has been shown that the internal nanostructures also affect cellular response such as cell uptake of nanoparticles, hemolysis, and cytotoxicity. 4 Importantly, the in vivo behavior of nanoparticles such as biodistribution appears to be regulated by their nanostructures. 5 However, it is difficult to predict and precisely control the mesophase behavior of these self-assembled nanomaterials, especially in complex systems with several components.
Abstract: Janus particles, which are named after the two-faced Roman god Janus, have two distinct sides with different surface features, structures, and compositions. This asymmetric structure enables the combination of different or even incompatible physical, chemical, and mechanical properties within a single particle. Much effort has been focused on the preparation of Janus particles with high homogeneity, tunable size and shape, combined functionalities, and scalability. With their unique features, Janus particles have attracted attention in a wide range of applications such as in optics, catalysis, and biomedicine. As a biomedical device, Janus particles offer opportunities to incorporate therapeutics, imaging, or sensing modalities in independent compartments of a single particle in a spatially controlled manner. This may result in synergistic actions of combined therapies and multi-level targeting not possible in isotropic systems. In this review, we summarize the latest advances in employing Janus particles as therapeutic delivery carriers, in vivo imaging probes, and biosensors. Challenges and future opportunities for these particles will also be discussed. Keywords: Janus particles, therapeutics, theranostics, imaging, sensing
Bone is prone to many complicated diseases and injuries. Hence, implant engineering is a critical healthcare challenge that addresses the increased need to efficiently replace the damaged tissue with functional bone-mimicking devices and mechanically reliable customised implants. Additive manufacturing (AM) offers a platform to fabricate customised patient-specific parts. However, despite favourable customisation outcomes, relatively few AM feedstock powders offer the biocompatibility required for medical implant and devices technologies. The process of developing feedstock that can be 3D printed into specific 3D structures while providing a favourable interface with the human tissue remains a challenge. Diamond-titanium (DTi) is a new composite that provides biocompatible 3D multi-material structures. Thus, we report herein a powder-deposition and print optimisation strategy to overcome the dual-functionality gap by printing bulk DTi parts. First, we provide details of the composite powder properties, flow analysis and printing-specific condition optimisation. Later we report structural integrity using Micro-CT and nanoindentation. We provide details of the design of the first 3D printed micro struts. Our approach offers a clear strategy to manufacture DTi parts with high integrity, performance, and biocompatibility, consequently expanding the material feedstock library and paving the way to diamond customised implants.
Bone infection remains a formidable challenge to the medical field. The goal of the current study is to evaluate antibacterial coatings in vitro and to develop a large animal model to assess coated bone implants. A novel coating consisting of titanium oxide and siloxane polymer doped with silver was created by metal-organic methods. The coating was tested in vitro using rapid screening techniques to determine compositions which inhibited Staphylococcus aureus growth, while not affecting osteoblast viability. The coating was then applied to intramedullary nails and evaluated in vivo in a caprine model. In this pilot study, a fracture was created in the tibia of the goat, and Staphylococcus aureus was inoculated directly into the bone canal. The fractures were fixed by either coated (treated) or non-coated intramedullary nails (control) for 5 weeks. Clinical observations as well as microbiology, mechanical, radiology, and histology testing were used to compare the animals. The treated goat was able to walk using all four limbs after 5 weeks, while the control was unwilling to bear weight on the fixed leg. These results suggest the antimicrobial potential of the hybrid coating and the feasibility of the goat model for antimicrobial coated intramedullary implant evaluation.
Iron oxide nanoparticles are promising candidates for drug delivery systems to treat osteoporosis due to their biocompatibility and magnetic properties. Magnetite and maghemite nanoparticles were synthesized here using a co-precipitation method. The particles were characterized by transmission electron microscopy (TEM). Effects of CaP coating iron oxide magnetic nanoparticles on the proliferation of osteoblasts (OB) were determined after 1, 3 and 5 days of culture. The correlation of iron oxide nanoparticle concentration on OB density was also investigated.
Self-assembled lyotropic liquid crystalline lipid nanoparticles have been developed for a wide range of biomedical applications with an emerging focus for use as delivery vehicles for drugs, genes, and in vivo imaging agents. In this study, we report the generation of lipid nanoparticle libraries with information regarding mesophase and lattice parameter, which can aid the selection of formulation for a particular end-use application. In this study we elucidate the phase composition parameters that influence the internal structure of lipid nanoparticles produced from monoolein, monopalmitolein and phytantriol incorporating a variety of saturated fatty acids (FA) with different chain lengths at varying concentrations and temperatures. The material libraries were established using high throughput formulation and screening techniques, including synchrotron small-angle X-ray scattering. The results demonstrate the rich polymorphism of lipid nanoparticles with nonlamellar mesophases in the presence of saturated FAs. The inclusion of saturated FAs within the lipid nanoparticles promotes a gradual phase transition at all temperatures studied toward structures with higher negative surface curvatures (e.g., from inverse bicontinuous cubic phase to hexagonal phase and then emulsified microemulsion). The three partial phase diagrams produced are discussed in terms of the influence of FA chain length and concentration on nanoparticle internal mesophase structure and lattice parameters. The study also highlights a compositionally dependent coexistence of multiple mesophases, which may indicate the presence of multicompartment nanoparticles containing cubic/cubic and cubic/hexagonal mesophases.
'/%3e%3c/defs%3e%3cpath fill='%23012169' d='M0 0h10080v5040H0z'/%3e%3cpath stroke='%23fff' stroke-width='.6' d='m0 0 6 3m0-3L0 3' clip-path='url(%23b)' transform='scale(840)'/%3e%3cpath stroke='%23e4002b' stroke-width='.4' d='m0 0 6 3m0-3L0 3' clip-path='url(%23c)' transform='scale(840)'/%3e%3cpath stroke='%23fff' stroke-width='840' d='M2520 0v2520M0 1260h5040'/%3e%3cpath stroke='%23e4002b' stroke-width='504' d='M2520 0v2520M0 1260h5040'/%3e%3cg fill='%23fff'%3e%3cuse xlink:href='%23d' x='2520' y='3780'/%3e%3cuse xlink:href='%23a' x='7560' y='4200'/%3e%3cuse xlink:href='%23a' x='6300' y='2205'/%3e%3cuse xlink:href='%23a' x='7560' y='840'/%3e%3cuse xlink:href='%23a' x='8680' y='1869'/%3e%3cuse xlink:href='%23e' x='8064' y='2730'/%3e%3c/g%3e%3c/svg%3e)
