Search Results (73)

Background/Objectives: Previous work in our lab demonstrated that a 3D scaffold containing lysine-modified chitosan (K-chitosan) and decorated with Matrilin-2 (MATN2) enhanced Schwann cell (SC) migration and axonal outgrowth in vitro and ex vivo. This study aimed to assess the regenerative effect of this scaffold compared to that of a collagen conduit and an autograft using a segmental rat sciatic nerve injury model. Methods: A total of 30 Lewis Rats were assigned into three groups: an untreated collagen conduit (UC) group, a collagen conduit treated with MATN2 K-chitosan (TC) group, and a reverse autograft (RA) group. Walking force measurements, compound muscle action potential (CMAP), the wet muscle weight of the tibialis anterior and the gastrocnemius, and axonal histomorphometry were assessed. Results: The walking force and CMAP were significantly higher in the TC group compared to those in the UC group, with no significant difference between the TC and RA groups. The muscle weights were significantly greater in the TC group compared to those in the UC group but smaller than those in the RA group. The TC group experienced significantly greater axonal regeneration compared to that with the UC, and no differences were found with the RA. The TC group further demonstrated significantly greater cell counts than those in the UC group and greater affinity of the Schwann cells towards nerve reconstruction. Conclusion: The MATN2 K-chitosan scaffold significantly improved nerve regeneration and was comparable to the RA, supporting the development of a novel bio-conductive scaffold conduit. Full article

Fusidic acid (FA), a tetracyclic triterpenoid, has been approved to treat methicillin-resistant Staphylococcus aureus (MRSA) infections. However, there are few reports about FA derivatives with high efficacy superior to FA, manifesting the difficulty of discovering the derivatives based on experience-based drug design. In this study, we employed a stepwise method to discover novel FA derivatives. First, molecular dynamics (MD) simulations were performed to identify the molecular mechanism of FA against elongation factor G (EF-G) and drug resistance. Then, we utilized a scaffold decorator to design novel FA derivatives at the 3- and 21-positions of FA. The ligand-based and structure-based screening models, including Chemprop and RTMScore, were employed to identify promising hits from the generated set. Ten generated FA derivatives with high efficacy in the Chemprop and RTMScore models were synthesized for in vitro testing. Compounds 4 and 10 demonstrated a 2-fold increase in potency against MRSA strains compared to FA. This study highlights the significant impact of AI-based methods on the design of novel FA derivatives with drug efficacy, which provides a new approach for drug discovery. Full article

Infection control and bone regeneration remain critical challenges in bone defect treatment. We developed a 3D-printed scaffold incorporating copper-based metal–organic framework-74 (Cu-MOF-74) within a polycaprolactone/hydroxyapatite composite. The synthesized Cu-MOF-74 exhibited a well-defined crystalline structure and rod-like morphology, as confirmed by TEM, EDS, FTIR, and XRD analyses. The scaffolds exhibited hierarchical pores (100–200 μm) and demonstrated tunable hydrophilicity, as evidenced by the water contact angles decreasing from 103.3 ± 2.02° (0% Cu-MOF-74) to 63.60 ± 1.93° (1% Cu-MOF-74). A biphasic Cu²⁺ release profile was observed from the scaffolds, reaching cumulative concentrations of 98.97 ± 3.10 ppm by day 28. Antimicrobial assays showed concentration-dependent efficacy, with 1% Cu-MOF-74 scaffolds achieving 90.07 ± 1.94% and 80.03 ± 2.17% inhibition against Staphylococcus aureus and Escherichia coli, respectively. Biocompatibility assessments using bone marrow-derived mesenchymal stem cells revealed enhanced cell proliferation at Cu-MOF-74 concentrations ≤ 0.2%, while concentrations ≥ 0.5% induced cytotoxicity. Osteogenic differentiation studies highlighted elevated alkaline phosphatase activity and mineralization in scaffolds with 0.05–0.2% Cu-MOF-74 scaffolds, particularly at 0.05% Cu-MOF-74 scaffolds, which exhibited the highest calcium deposition and upregulation of bone sialoprotein and osteopontin expression. These findings demonstrate the dual functional efficacy of Cu-MOF-74/PCL/HAp scaffolds in promoting both infection control and bone regeneration. These optimized Cu-MOF-74 concentrations (0.05–0.2%) effectively balance antimicrobial and osteogenic properties, presenting a promising strategy for bone defect repair in clinical applications. 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 limited range of available flu treatments due to virus mutations and drug resistance have prompted the search for new therapies. RNA-dependent RNA polymerase (RdRp) is a heterotrimeric complex of three subunits, i.e., polymerase acidic protein (PA) and polymerase basic proteins 1 and 2 (PB1 and PB2). It is widely recognized as one of the most promising anti-flu targets because of its critical role in influenza infection and high amino acid conservation. In particular, the disruption of RdRp complex assembly through protein–protein interaction (PPI) inhibition has emerged as a valuable strategy for discovering a new therapy. Our group previously identified the 3-cyano-4,6-diphenyl-pyridine core as a privileged scaffold for developing PA–PB1 PPI inhibitors. Encouraged by these findings, we synthesized a small library of pyridine and pyrimidine derivatives decorated with a thio-N-(m-tolyl)acetamide side chain (compounds 2a–n) or several amino acid groups (compounds 3a–n) at the C2 position. Interestingly, derivative 2d, characterized by a pyrimidine core and a phenyl and 4-chloro phenyl ring at the C4 and C6 positions, respectively, showed an IC₅₀ value of 90.1 μM in PA–PB1 ELISA, an EC₅₀ value of 2.8 μM in PRA, and a favorable cytotoxic profile, emerging as a significant breakthrough in the pursuit of new PPI inhibitors. A molecular modeling study was also completed as part of this project, allowing us to clarify the biological profile of these compounds. Full article

Neutrophils release neutrophil extracellular traps (NETs) as a defense strategy in response to broad-spectrum infections and sterile triggers. NETs consist of a DNA scaffold decorated with antimicrobial peptides (AMPs) and enzymatically active proteases, including peptidyl arginine deiminase type 4 (PAD4). Susceptibility to infections and inflammatory dysregulation are hallmarks of alcohol-related liver disease (ALD). Sixty-two patients with ALD were prospectively recruited, and they were followed for 90 days. Twenty-four healthy volunteers served as the control group. PAD4 concentrations were quantified using immunoenzymatic ELISAs. Correlation coefficients between PAD4 blood concentrations and markers of systemic inflammation; liver dysfunction severity scores; and ALD complications were calculated. The receiver operating curves (ROCs) and their areas under the curve (AUCs) were checked in order to assess the accuracy of PAD4 expression in predicting the degree of liver failure and the development of ALD complications. Systemic concentrations of PAD4 were significantly increased in the patients with ALD in comparison with controls. PAD4 levels correlated with the standard markers of inflammation and revealed a good predictive AUC (0.76) for survival in the whole ALD group. PAD4 seems to be an inflammatory mediator and may be potentially applied as a predictor of patient survival in ALD. Full article

Sluggish transfer kinetics caused by solid–solid contact at the lithium (Li)/solid-state electrolyte (SE) interface is an inherent drawback of all-solid-state Li metal batteries (ASSLMBs) that not only limits the cell power density but also induces uneven Li deposition as well as high levels of interfacial stress that deteriorates the internal structure and cycling stability of ASSLMBs. Herein, a fast Li⁺ transfer scaffold is proposed to overcome the sluggish kinetics at the Li/SE interface in ASSLMBs using an α-MnO₂-decorated carbon paper (CP) structure (α-MnO₂@CP). At an atomic scale, the tunnel structure of α-MnO₂ exhibits a great ability to facilitate Li⁺ adsorption and transportation across the inter-structure of α-MnO₂@CP, leading to a high critical current density of 3.95 mA cm⁻² at the Li/SE interface. Meanwhile, uniform Li deposition can be guided along the skeletons of α-MnO₂@CP with minimized volume expansion, significantly improving the structural stability of the Li/SE interface. Based on these advantages, the ASSLMBs using α-MnO₂@CP protected the Li anode and can stably cycle up to very high charge/discharge rates of 10C/10C, paving the way for developing high-power ASSLMBs. Full article

This study aimed to develop a polymeric matrix of polyamide-6 (P6) impregnated with trimetaphosphate (TMP) nanoparticles and silver nanoparticles (AgNPs), and to evaluate its antimicrobial activity, surface free energy, TMP and Ag⁺ release, and cytotoxicity for use as a support in dental tissue. The data were subjected to statistical analysis (p < 0.05). P6 can be incorporated into TMP without altering its properties. In the first three hours, Ag⁺ was released for all groups decorated with AgNPs, and for TMP, the release only occurred for the P6-TMP-5% and P6-TMP-10% groups. In the inhibition zones, the AgNPs showed activity against both microorganisms. The P6-TMP-2.5%-Ag and P6-TMP-5%-Ag groups with AgNPs showed a greater reduction in CFU for S. mutans. For C. albicans, all groups showed a reduction in CFU. The P6-TMP groups showed higher cell viability, regardless of time (p < 0.05). The developed P6 polymeric matrix impregnated with TMP and AgNPs demonstrated promising antimicrobial properties against the tested microorganisms, making it a potential material for applications in scaffolds in dental tissues. Full article

The use of privileged scaffolds as a starting point for the construction of libraries of bioactive compounds is a widely used strategy in drug discovery and development. Scaffold decoration, morphing and hopping are additional techniques that enable the modification of the chosen privileged framework and better explore the chemical space around it. In this study, two series of highly functionalized pyrimidine and pyridine derivatives were synthesized using a scaffold morphing approach consisting of triazine compounds obtained previously as antiviral agents. Newly synthesized azines were evaluated against lymphoma, hepatocarcinoma, and colon epithelial carcinoma cells, showing in five cases acceptable to good anticancer activity associated with low cytotoxicity on healthy fibroblasts. Finally, ADME in vitro studies were conducted on the best derivatives of the two series showing good passive permeability and resistance to metabolic degradation. Full article

A nanofibrous layer of polyvinylpyrrolidone (PVP) was designed to house, both in the fiber core and onto its outer surface, nanoparticles of mesoporous graphene (MGC), which are able to selectively adsorb acetic acid vapors. When grown on interdigital fingers microelectrodes (IDEs), upon UV-light irradiation taking place in air, the layer proved conductive and stable. Electrical and sensing features were significatively modulated by decorating the fiber surface with MGC (a sandwich-like structure) and polyethyleneimine (PEI). MGC, used both as a conductive filler and to decorate the fiber surface, strengthened the PVP scaffold and acted as a nucleation center for entrapping molecules of acetic acid. PEI improved the adhesion of MGC onto the surface. A preliminary study reported fast responses, high sensitivity with good linearity, selectivity, reversibility, and repeatability towards the acetic acid in ranges of up to hundreds of ppm at room temperature. Full article

Mesoporous bioactive glasses (MBGs) of the SiO₂–CaO–P₂O₅ system are biocompatible materials with a quick and effective in vitro and in vivo bioactive response. MBGs can be enhanced by including therapeutically active ions in their composition, by hosting osteogenic molecules within their mesopores, or by decorating their surfaces with mesenchymal stem cells (MSCs). In previous studies, our group showed that MBGs, ZnO-enriched and loaded with the osteogenic peptide osteostatin (OST), and MSCs exhibited osteogenic features under in vitro conditions. The aim of the present study was to evaluate bone repair capability after large bone defect treatment in distal femur osteoporotic rabbits using MBGs (76%SiO₂–15%CaO–5%P₂O₅–4%ZnO (mol-%)) before and after loading with OST and MSCs from a donor rabbit. MSCs presence and/or OST in scaffolds significantly improved bone repair capacity at 6 and 12 weeks, as confirmed by variations observed in trabecular and cortical bone parameters obtained by micro-CT as well as histological analysis results. A greater effect was observed when OST and MSCs were combined. These findings may indicate the great potential for treating critical bone defects by combining MBGs with MSCs and osteogenic peptides such as OST, with good prospects for translation to clinical practice. Full article

Scaffolds have been used to promote periodontal regeneration by providing control over the spacio-temporal healing of the periodontium (cementum, periodontal ligament (PDL) and alveolar bone). This study proposes to enhance the biofunctionality of a biphasic scaffold for periodontal regeneration by means of cell-laid extracellular matrix (ECM) decoration. To this end, a melt electrowritten scaffold was cultured with human osteoblasts for the deposition of bone-specific ECM. In parallel, periodontal ligament cells were used to form a cell sheet, which was later combined with the bone ECM scaffold to form a biphasic PDL–bone construct. The resulting biphasic construct was decellularised to remove all cellular components while preserving the deposited matrix. Decellularisation efficacy was confirmed in vitro, before the regenerative performance of freshly decellularised constructs was compared to that of 3-months stored freeze-dried scaffolds in a rodent periodontal defect model. Four weeks post-surgery, microCT revealed similar bone formation in all groups. Histology showed higher amounts of newly formed cementum and periodontal attachment in the fresh and freeze-dried ECM functionalised scaffolds, although it did not reach statistical significance. This study demonstrated that the positive effect of ECM decoration was preserved after freeze-drying and storing the construct for 3 months, which has important implications for clinical translation. Full article

Excited State Intramolecular Proton Transfer (ESIPT), originally discovered and explored in depth in a number of extensive photophysical studies, is more recently rediscovered as a powerful synthetic tool, offering rapid access to complex polyheterocycles. In our prior work we have employed ESIPT in aromatic o-keto amines and amides, leading to diverse primary photoproducts—complex quinolinols or azacanes possessing a fused lactam moiety—which could additionally be modified in short, high-yielding postphotochemical reactions to further grow complexity of the heterocyclic core scaffold and/or to decorate it with additional functional groups. Given that sulfonamides are generally known as privileged substructures, in this study we pursued two goals: (i) To explore whether sulfonamides could behave as proton donors in the context of ESIPT-initiated photoinduced reactions; (ii) To assess the scope of subsequent complexity-building photochemical and postphotochemical steps, which give access to polyheterocyclic molecular cores with fused cyclic sulfonamide moieties. In this work we show that this is indeed the case. Simple sulfonamide-containing photoprecursors produced the sought-after heterocyclic products in experimentally simple photochemical reactions accompanied by significant step-normalized complexity increases as corroborated by the Böttcher complexity scores. Full article

Three-dimensional (3D) printing technology has become a popular tool to produce complex structures. It has great potential in the regenerative medicine field to produce customizable and reproducible scaffolds with high control of dimensions and porosity. This study was focused on the investigation of new biocompatible and biodegradable 3D-printed scaffolds with suitable mechanical properties to assist tendon and ligament regeneration. Polylactic acid (PLA) scaffolds were reinforced with 0.5 wt.% of functionalized graphite nanoplatelets decorated with silver nanoparticles ((f-EG)+Ag). The functionalization of graphene was carried out to strengthen the interface with the polymer. (f-EG)+Ag exhibited antibacterial properties against Staphylococcus aureus (S. aureus) and Escherichia coli (E. coli), an important feature for the healing process and prevention of bacterial infections. The scaffolds’ structure, biodegradation, and mechanical properties were assessed to confirm their suitability for tendon and ligamentregeneration. All scaffolds exhibited surface nanoroughness created during printing, which was increased by the filler presence. The wet state dynamic mechanical analysis proved that the incorporation of reinforcement led to an increase in the storage modulus, compared with neat PLA. The cytotoxicity assays using L929 fibroblasts showed that the scaffolds were biocompatible. The PLA+[(f-EG)+Ag] scaffolds were also loaded with human tendon-derived cells and showed their capability to maintain the tenogenic commitment with an increase in the gene expression of specific tendon/ligament-related markers. The results demonstrate the potential application of these new 3D-printed nanocomposite scaffolds for tendon and ligament regeneration. Full article

With the aim to propose innovative antimicrobial agents able to not only selectively inhibit bacterial carbonic anhydrases (CAs) but also to be photoactivated by specific wavelengths, new heptamethine-based compounds decorated with a sulfonamide moiety were synthesized by means of different spacers. The compounds displayed potent CA inhibition and a slight preference for bacterial isoforms. Furthermore, minimal inhibitory and bactericidal concentrations and the cytotoxicity of the compounds were assessed, thus highlighting a promising effect under irradiation against S. epidermidis. The hemolysis activity test showed that these derivatives were not cytotoxic to human red blood cells, further corroborating their favorable selectivity index. This approach led to the discovery of a valuable scaffold for further investigations. Full article