Search Results (2,086)

Background/Objectives: The rapid evolution of bacterial resistance and the high cost of drug development have attributed greatly to the dearth in drug design. Computational approaches and natural product exploitation offer potential solutions to accelerate drug discovery. Methods: In this research article, we aimed to identify novel antibacterial hits. For the in silico studies, molecular scaffolds from the in-house chemical library of the Department of Pharmacy of Athens (Pharmalab) and the National Cancer Institute (NCI) were screened and selected for further experimental procedures. Compounds from both libraries that were not previously screened for their antimicrobial properties were tested in vitro against Gram-positive and Gram-negative bacterial strains. The microdilution method was used to determine the minimum inhibitory concentrations (MICs). Results: In silico screening identified twenty promising molecules from the NCI and seven from the Pharmalab databases. The unexplored compounds for their antibacterial activity can be characterized as weak strain-specific antimicrobials. The NSC 610491 and NSC 610493 were active against Staphylococcus aureus (MIC: 25 and 12.5 µg/mL, respectively) and methicillin-resistant S. aureus (MRSA) (MIC: 50 and 12.5 µg/mL, respectively). Six out of seven hydroxytyrosol (HTy) compounds were moderately active (MIC: 25–50 µg/mL) against S. aureus, MRSA and Enterococcus faecalis. For the Gram-negative bacteria, no activity was detected (≥100 µg/mL). Conclusions: The tested scaffolds could be considered as promising candidates for novel antimicrobials with improvements. Further experimentation is required to assess mechanisms of action and evaluate the efficacy and safety. Full article

Phosphate invert glasses (PIGs) have been attracting attention as materials for bone repair. PIGs have a high flexibility in chemical composition because they are composed of orthophosphate and pyrophosphate and can easily incorporate various ions in their glass networks. In our previous work, incorporation of niobium (Nb) into melt-quench-derived PIGs was effective in terms of controlling their ion release, and Nb ions promoted the activity of osteoblast-like cells. In the present work, a liquid-phase method was used for synthesizing Nb-containing PIGs, as this method allows us to prepare a glass precursor solution at room temperature, which can be attributed to improved glass-shape design. Nb-containing PIGs were successfully prepared, and their ion release behavior was controlled by changing the Nb content in the PIGs. The functions of Nb varied according to its content. For example, in the case of PIGs containing a larger amount of Nb, Nb acted as both the network modifier and former while also inducing the formation of chain-like structures. These glasses possessed a gradual ion release in a tris-HCl buffer solution. Cotton-wool-like structured scaffolds were fabricated using the synthesized Nb-containing glass using a wet-spinning method. Because the scaffolds possess excellent flexibility and controllable ion release, they are good candidates for new biomaterials. Full article

The direct ink writing (DIW) process has been successfully used to prepare SiC-based composites from preceramic polymers due to the porous light weight, lower sintering temperature, and tailored design. However, it still presents challenges in improving the mechanical properties of composites and endowing them with multifunctionality. In this study, we present a 3D-printing strategy for preparing a graphene/SiC_p/SiC composite using the DIW process. A polycarbosilane (PCS)-based slurry containing graphene/SiC_p composite powder was developed and 3D-printed into scaffolds with a lattice structure, which were then pyrolyzed at 1500 °C to obtain a graphene/SiC_p/SiC composite. The weight loss, viscosity, and printability of the graphene/SiC_p/PCS slurry were evaluated, and it was determined that the slurry after 4 h of magnetic stirring was suitable for the DIW process. When heat-treated at above 800 °C in an N₂ atmosphere, PCS was first reacted with SiC_xO_y, which was further transformed into β-SiC and pyrocarbon. The 3D-printed lattice structure achieved porosity and low density, while the SiC_p reduced defects caused by large shrinkage during pyrolysis of PCS. Meanwhile, GNPs provided the composites with better conductivity and lower density. The density was as low as 1.08 g/cm³, the conductivity reached 670 S·m⁻¹, and the compressive strength was 4.3 MPa. Thus, a lightweight and porous SiC-based composite with high conductivity and strength can be prepared. Full article

In this study, we present novel, vitrimeric and biobased scaffolds that are designed for hard tissue applications, composed of acrylated, epoxidized soybean oil (AESO) and reinforced with bioactive glass that is Tellurium doped (BG-Te) and BG-Te silanized, to tune the mechanical and antibacterial properties. The manufacture’s method consisted of a DLP 3D-printing method, enabling precise resolution and the possibility to manufacture a hollow and complex structure. The resin formulation was optimized with a biobased, reactive diluent to adjust the viscosity for an optimal 3D-printing process. The in vitro biological evaluation of the 3D-printed scaffolds, combined with BG-Te and BG-Te-Sil, showed that the sample’s surfaces remained safe for hBMSCs’ attachment and proliferation. The number of S. aureus that adhered to the BG-Te was 87% and 54% lower than on the pristine (control) and BG-Te-Sil, respectively, with the eradication of microbiofilm aggregates. This work highlights the effect of the vitrimeric polymer matrix and doped, bioactive glass in manufacturing biocompatible, biobased, and antibacterial scaffold used in hard tissue application. Full article

We report the design and development of a novel multifunctional nanostructure, RB-AuSiO₂_HSA-DOX, where tri-modal cancer treatment strategies—photothermal therapy (PTT), photodynamic therapy (PDT), chemotherapy—luminescent properties and targeting are integrated into the same scaffold. It consists of a gold core with optical and thermo-plasmonic properties and is covered by a silica shell entrapping a well-known photosensitizer and luminophore, Rose Bengal (RB). The nanoparticle surface was decorated with Human Serum Albumin (HSA) through a covalent conjugation to confer its targeting abilities and as a carrier of Doxorubicin (DOX), one of the most effective anticancer drugs in clinical chemotherapy. The obtained nanostructure was fully characterized through transmission electron microscopy (TEM), dynamic light scattering (DLS) and UV-visible spectroscopy, with a homogeneous and spherical shape, an average diameter of about 60 nm and negative ζ-potential value Singlet oxygen generation and photothermal properties were explored under green light irradiation. The interaction between DOX-HSA anchored on the nanoplatform was investigated by fluorescence spectroscopy and compared to that of DOX-HSA, pointing out different accessibility of the drug molecules to the HSA binding sites, whether the protein is free or bound to the nanoparticle surface. To the best of our knowledge, there are no studies comparing a drug–HSA interaction with that of the same protein anchored to nanoparticles. Furthermore, the uptake of RB-AuSiO₂_HSA-DOX into MDA-MB-231 mammary cells was assessed by confocal imaging, highlighting—at early time of incubation and as demonstrated by the increased DOX luminescence displayed within cells—a better internalization of the carried anticancer drug compared to the free one, making the obtained nanostructure a suitable and promising platform for an anticancer multimodal approach. Full article

The prototype of a biomimetic multi-spiked connecting scaffold (MSC-Scaffold) represents an essential innovation in the fixation in subchondral trabecular bone of components for a new generation of entirely cementless hip resurfacing arthroplasty (RA) endoprostheses. In designing such a functional biomaterial scaffold, identifying the microstructural and mechanical properties of the host bone compromised by degenerative disease is crucial for proper post-operative functioning and long-term maintenance of the endoprosthesis components. This study aimed to explore, depending on the occurrence of obesity, changes in the microstructure and mechanical properties of the subchondral trabecular bone in femoral heads of osteoarthritis (OA) patients caused by the MSC-Scaffold embedding. Computed microtomography (micro-CT) scanning of femoral heads from OA patients was conducted before and after the mechanical embedding of the MSC-Scaffold. Bone morphometric parameters such as bone volume/total volume (BV/TV), trabecular thickness (Tb.Th), and trabecular number (Tb.N) for regions surrounding the MSC-Scaffold were computed, and the mechanical properties such as bone density (ρ_B), bone compressive strength (S), and the Young’s modulus (E) within these regions were calculated. A statistically significant increase in BV/TV (by 15.0% and 24.9%) and Tb.Th (by 13.1% and 42.5%) and a decrease in Tb.N (by 15.2% and 23.6%) were observed, which translates to an increase in ρ_B (by 15.0% and 24.9%), S (by 28.8% and 49.5%), and E (by 18.0% and 29.8%) in non-obese patients and obese patients, respectively. These changes in properties are favorable for the mechanical loads’ transfer from the artificial joint surface via the MSC-Scaffold to the periarticular trabecular bone of the OA femoral head in the postoperative period. Full article

Chronic wounds represent a persistent clinical challenge due to prolonged inflammation and impaired tissue repair mechanisms. Cannabidiol (CBD), recognized for its anti-inflammatory and pro-healing properties, shows therapeutic promise in wound care. However, its delivery via lipid nanoparticles (LNPs) remains challenging due to CBD’s inherent instability and low bioavailability. This study developed and characterized a novel hydrogel scaffold composed of CBD-loaded LNPs (CBD/LNPs) integrated into a polyvinyl alcohol (PVA) and sodium alginate (SA) matrix, designed to enhance wound repair and mitigate inflammation. The characteristics of the hydrogel scaffold were observed including the degree of swelling and LNPs’ release profiles. Furthermore, in the results, CBD/LNPs displayed enhanced stability and reduced cytotoxicity compared to unencapsulated CBD. In vitro assays demonstrated that CBD/LNPs significantly promoted fibroblast migration in gap-closure wound models and reduced intracellular reactive oxygen species, supporting their potential as a biocompatible and efficacious agent for cellular repair and oxidative stress attenuation. In vivo experiments using adult male Wistar rats with aseptic cutaneous wounds revealed that treatment with CBD/LNP-PVA/SA hydrogel scaffold significantly accelerated wound closure relative to blank hydrogel controls, demonstrating a substantial reduction in the wound area over time. Histological analysis confirms notable improvements in skin morphology in wounds treated with CBD/LNP-PVA/SA hydrogel scaffold with evidence of accelerated epithelialization, enhanced collagen deposition, and increased dermal thickness and vascularization. Additionally, skin histology showed a more organized epidermal layer and reduced inflammatory cell infiltration in CBD/LNP-PVA/SA hydrogel scaffold-treated wounds, corresponding to a 35% increase in the wound closure rate by day 28 post-treatment. These findings suggest that CBD/LNP-PVA/SA hydrogel scaffolds facilitate inflammation resolution and structural wound healing through localized, sustained CBD delivery. The dual anti-inflammatory and wound-healing effects position CBD/LNP-PVA/SA hydrogel scaffold as a promising approach for chronic wound management. Future investigations are warranted to elucidate the mechanistic pathways by which CBD modulates the skin architecture and to explore its translational applications in clinical wound care. Full article

Bacterial-infected skin wounds caused by trauma remain a significant challenge in modern medicine. Clinically, there is a growing demand for wound dressings with exceptional antibacterial activity and robust regenerative properties. To address the need, this study proposes a novel multifunctional dressing designed to combine efficient gas exchange, effective microbial barriers, and precise drug delivery capabilities, thereby promoting cell proliferation and accelerating wound healing. This work reports the development of a 3D-printed hydrogel scaffold incorporating flavanone (FLA)-loaded ZIF-8 nanoparticles (FLA@ZIF-8 NPs) within a composite matrix of κ-carrageenan (KC) and konjac glucomannan (KGM). The scaffold forms a stable dual-network structure through the chelation of KC with potassium ions and intermolecular hydrogen bonding between KC and KGM. This dual-network structure not only enhances the mechanical stability of the scaffold but also improves its adaptability to complex wound environments. In mildly acidic wound conditions, FLA@ZIF-8 NPs release Zn²⁺ and flavanone in a controlled manner, providing sustained antibacterial effects and promoting wound healing. In vivo studies using a rat full-thickness infected wound model demonstrated that the FLA@ZIF-8/KC@KGM hydrogel scaffold significantly accelerated wound healing, showcasing its superior performance in the treatment of infected wounds. Full article

24Z-Masticadienonic acid (MNA) and 24Z-isomasticadienonic acid (IMNA) are the major triterpenic acids in Chios Mastic Gum (CMG), a resin derived from Pistacia lentiscus var. Chia. Despite their promising pharmacological potential, limited information is available due to the complexity of isolating them in pure form. This study developed a chemo-selective method for isolating MNA and IMNA and investigated their chemical transformation through isomerization of the external double bond and A-ring contraction of the triterpene scaffold. A rapid method for isolating MNA from CMG was first established, followed by a high-yield acid-catalyzed procedure to obtain both 24Z and 24E isomers of IMNA. Additionally, a basic catalyzed isomerization of IMNA led to the formation of two new compounds with A-ring contraction, which could serve as novel scaffolds for the design of new triterpene analogs. The mixture of MNA/IMNA, along with the individual compounds and their semi-synthetic analogs, exhibited significant anti-inflammatory activity. Notably, 24E-isomasticadienonic acid and 24Z-2-hydroxy-3-oxotirucalla-1,8,24-trien-26-oic acid, a previously unreported compound, significantly reduced the mRNA expression levels of Tnf, Il6, and Nfkb1 in RAW 264.7 macrophage cells. Full article

Background: Fibroblast activation protein (FAP)-targeted theranostic radiopharmaceuticals have shown desired tumor-to-background organ selectivity due to the ubiquitous presence of FAP within the tumor microenvironment. However, suboptimal tumor retention and fast clearance have hindered their use to deliver effective cancer therapies. With well-documented FAP-targeting moieties and linkers appending them to optimal chelators, the development of copper radiopharmaceuticals has attracted considerable interest, given the fact that an ideal theranostic pair of copper radionuclides (⁶⁴Cu: t_1/2 = 12.7 h; 17.4% β⁺; E_β⁺_max = 653 keV and ⁶⁷Cu: t_1/2 = 2.58 d; 100% β⁻; E_β⁻_max = 562 keV) are available. Herein, we report our design, synthesis, and comparative evaluation of monovalent and divalent FAP-targeted theranostic conjugates constructed from our previously reported bifunctional chelator scaffold (BFS) based on 1,4,8,11-tetraaza-bicyclo [6.6.2]hexadecane-4,11-diacetic acid (CB-TE2A), which forms the most stable complex with Cu(II). Methods: After synthesis and characterization, the monovalent and divalent conjugates were radiolabeled with ⁶⁴Cu for in vitro cell assays, followed by in vivo positron emission tomography (PET) imaging evaluation in relevant mouse models. Results: Both ⁶⁴Cu-labeled conjugates showed high in vitro stability and anticipated FAP-mediated cell binding and internalization. The divalent one showed significantly higher FAP-specific tumor uptake than its monovalent counterpart. Conclusions: Our results demonstrate that the BFS-based multivalent approach can be practically used to generate FAP-targeted radiotheranostic agents for effective cancer diagnosis and treatment. Full article

In this study, we synthesized a series of 3-hydroxy-4-pyridinone (3,4-HPO) chelators with varying lipophilicity by modifying the length of their alkyl chains. To investigate their interaction with lipid membranes, we employed differential scanning calorimetry (DSC) and electron paramagnetic resonance (EPR) spectroscopy using dimyristoylphosphatidylcholine (DMPC) and palmitoyloleoylphosphatidylcholine (POPC) liposomes as membrane model systems. DSC experiments on DMPC liposomes revealed that hexyl-substituted chelators significantly altered the thermotropic phase behavior of the lipid bilayer, indicating their potential as membrane property modulators. EPR studies on DMPC and POPC liposomes provided detailed insights into the depth-dependent effects of chelators on membrane fluidity. Our findings highlight the crucial role of alkyl chain length in determining the interaction of 3,4-HPO chelators with lipid membranes and offer valuable insights for the design of lipid-interacting therapeutic agents based on this scaffold. Full article

Bionic bioceramic scaffolds are essential for achieving excellent implant properties and biocompatible behavior. In this study, inspired by the microstructure of natural bone, bionic hydroxyapatite (HAp) ceramic scaffolds with different structures (body-centered cubic (BCC), face-centered cubic (FCC), and gyroid Triply Periodic Minimal Surfaces (TPMSs)) and porosities (80 vol.%, 60 vol.%, and 40 vol.%) were designed, 3D-printed, and characterized. The effects of structure and porosity on the morphology, mechanical properties, and in vitro biocompatibility properties of the HAp scaffolds were studied and compared with each other. Interestingly, the HAp scaffold with a porosity of 80 vol.% and a TPMS structure had the best combination of compressive strength and in vitro biocompatibility, and demonstrated a great biomedical application potential for bone repair. We hope this study can provide a reference for the application and development of HAp scaffolds in the field of bone repair engineering. Full article

The advancement of synthetic host–guest chemistry has played a pivotal role in exploring and quantifying weak non-covalent interactions, unraveling the intricacies of molecular recognition in both chemical and biological systems. Macrocycles, particularly calix[4]resorcinarene-based cavitands, have demonstrated significant utility in receptor design, facilitating the creation of intricately organized architectures. Within the realm of macrocycles, these cavitands stand out as privileged scaffolds owing to their synthetic adaptability, excellent topological structures, and unique recognition properties. So far, extensive investigations have been conducted on various applications of calix[4]resorcinarene-based cavitands. In this review, we will elaborate on their diverse functions, including catalysis, separation and purification, polymeric materials, sensing, battery materials, as well as drug delivery. This review aims to provide a holistic understanding of the multifaceted roles of calix[4]resorcinarene-based cavitands across various applications, shedding light on their contributions to advancing the field of supramolecular chemistry. Full article

Multicomponent oxide systems have many applications in different fields such as optics and medicine. In this work, we developed new hybrid photoresists based on a combination of an organic acrylate resin and an inorganic sol, suitable for 3D printing via two-photon polymerization (2PP). The inorganic sol contained precursors of a binary SiO₂-CaO or a ternary SiO₂-CaO-P₂O₅ system. Complex microstructures were 3D printed using these hybrid photoresists and 2PP. The obtained materials were characterized using thermogravimetric analysis (TGA), Fourier transform infrared spectroscopy (FTIR), and scanning electron microscopy (SEM) techniques. Our results revealed that the produced microstructures were able to endure sintering at 700 °C without collapsing, leading to scaffolds with 235 and 355 nm resolution and pore size, respectively. According to the TGA analysis, there was no significant mass loss beyond 600 °C. After sintering at 500 °C, the FTIR spectra showed the disappearance of the characteristic bands associated with the organic phase, and the presence of bands characteristic of the binary and ternary oxide systems and carbonate groups. The SEM images showed different morphologies of agglomerated nanoparticles with mean sizes of about 20 and 60 nm for ternary and binary systems, respectively. Our findings open the way towards precise control of bioglass scaffold fabrication with tremendous design flexibility. Full article

Muscle stem cells (MuSCs) are essential for skeletal muscle regeneration, influenced by a complex interplay of mechanical, biochemical, and molecular cues. Properties of the extracellular matrix (ECM) such as stiffness and alignment guide stem cell fate through mechanosensitive pathways, where forces like shear stress translate into biochemical signals, affecting cell behavior. Aging introduces senescence which disrupts the MuSC niche, leading to reduced regenerative capacity via epigenetic alterations and metabolic shifts. Transplantation further challenges MuSC viability, often resulting in fibrosis driven by dysregulated fibro-adipogenic progenitors (FAPs). Addressing these issues, scaffold designs integrated with pharmacotherapy emulate ECM environments, providing cues that enhance graft functionality and endurance. These scaffolds facilitate the synergy between mechanotransduction and intracellular signaling, optimizing MuSC proliferation and differentiation. Innovations utilizing human pluripotent stem cell-derived myogenic progenitors and exosome-mediated delivery exploit bioactive properties for targeted repair. Additionally, 3D-printed and electrospun scaffolds with adjustable biomechanical traits tackle scalability in treating volumetric muscle loss. Advanced techniques like single-cell RNA sequencing and high-resolution imaging unravel muscle repair mechanisms, offering precise mapping of cellular interactions. Collectively, this interdisciplinary approach fortifies tissue graft durability and MuSC maintenance, propelling therapeutic strategies for muscle injuries and degenerative diseases. Full article