Search Results (98)

Mesoporous bioactive glass nanoparticles (MBGNs) are promising for bone tissue engineering; however, surgical site infection and oxidative stress often compromise regeneration. To address this, MBGNs co-doped with cerium (Ce), zinc (Zn), and strontium (Sr) were synthesized using a microemulsion-assisted sol-gel route (xCe-yZn-Sr-MBGNs; x = 0, 1, 2; y = 0, 0.5, 1). The resulting spherical nanoparticles (150–200 nm) exhibited a mesoporous structure with a specific surface area of (~340–425 m²/g), sustained ion release, and apatite formation in simulated body fluid. In vitro evaluations with MC3T3-E1 pre-osteoblasts demonstrated dose-dependent cytocompatibility, specifically in the co-doped formulations; however, higher Ce concentrations (2Ce-yZn-Sr-MBGNs) reduced viability following prolonged exposure. Crucially, the 1Ce-1Zn-Sr-MBGNs significantly enhanced osteogenic differentiation, as evidenced by a two-fold increase in osteogenic marker gene expression and a ~45% increase in calcium mineral deposition compared to undoped MBGNs within 14 days. Moreover, these particles accelerated cell migration, achieving ~70% scratch-wound closure within 24 h. Furthermore, 1Ce-1Zn-Sr-MBGNs displayed strong radical scavenging capacity and potent antibacterial activity against S. aureus and P. aeruginosa. These findings indicated that 1Ce-1Zn-Sr-MBGNs exhibited multiple therapeutic effects, including antibacterial, radical-scavenging, and osteogenic effects. By optimizing dopant ratios, these multifunctional nanomaterials emerge as promising candidates for next-generation bone grafts or implant coatings. Within the scope of this study, they demonstrated the capacity to simultaneously address three critical challenges in bone healing: controlling infection, mitigating oxidative stress, and promoting mineralized tissue formation. While these in vitro results provide a robust foundation, further in vivo validation is warranted to confirm their efficacy within complex physiological environments. Full article

The conversion of lignocellulosic biomass (LCB) into biofuels is hindered by its inherent resistance and the drawbacks of conventional pretreatment, which include high cost, intensive energy use, and inhibitor formation. Here, we present a novel, one-pot bioconversion process that bypasses pretreatment by integrating cerium-doped iron oxide nanoparticles (CeFeO₄NPs) with a specialized enzyme system. The system utilizes enzyme supernatant from Penicillium janthinellum mutant EU-30, a strain developed via chemical–physical mutagenesis, which exhibits stable hemicellulase activity and a 25–30% increase in cellulase activity. The integrated approach effectively saccharified raw sugarcane bagasse (SB) within 24 h, generating the highest yields of 12.8 ± 0.5 g/L glucose and 11.54 ± 0.5 g/L xylose compared to other substrates tested. Subsequent fermentation with Saccharomyces cerevisiae yielded 13.47 g/L ethanol (1.21 g/L/h productivity) and demonstrated concurrent consumption of both hexose and pentose sugars. We propose that residual CeFe₃O₄NPs in the hydrolysate mitigate carbon catabolite inhibition, thereby increasing xylose utilization. This was attributed to the residual CeFe₃O₄NPs in the hydrolysate, which are thought to upregulate xylose-metabolism-related genes in S. cerevisiae, thereby alleviating carbon catabolite inhibition. This method offers a streamlined, economical, and sustainable platform for producing carbon-neutral bioethanol from agricultural waste, eliminating costly pretreatment and simplifying downstream processing. Full article

Titanium dioxide nanotubes (TNTs) have favorable biocompatibility and nanoscale morphologies, and they have been extensively explored for titanium implant surface modifications. However, they are limited by their mechanical strength and weak interfacial adhesion between the nanotube layer and the titanium substrate. This restricts their clinical applications. In this study, a two-step electrochemical anodization method is developed to achieve in situ tantalum (Ta) doping into TNT arrays to enhance their mechanical performance without altering their nanotubular structure. The surface morphology, element and crystal phase composition, surface roughness, wettability, and mechanical properties of the Ta-doped TNTs were then thoroughly characterized. Scanning electron microscopy revealed that the Ta doping did not change the nanotube architecture. In addition, X-ray diffraction confirmed anatase TiO₂ formation in all the samples. X-ray photoelectron spectroscopy demonstrated that Ta⁵⁺ doping significantly reduced oxygen vacancies, and this was a concentration-dependent effect. Nanoindentation and scratch tests showed that the hardness, the Young’s modulus of the nanotube layer, and the adhesion strength between the nanotubes and the titanium substrate were markedly improved compared to those of the undoped TNTs. These mechanical enhancements may be attributed to lattice densification due to Ta doping. In vitro cell assays further demonstrated that the Ta-TNTs promoted rat bone marrow mesenchymal stem cell adhesion, proliferation, and osteogenic differentiation. This was evidenced by increased alkaline phosphatase activity, enhanced mineralization, and upregulated gene expression levels. The results suggest that the Ta-doped TNTs offer a pathway for the development of mechanically robust and bioactive implant surfaces for dental and orthopedic applications. Full article

Lipid nanoparticles (LNPs) are now the go-to method for delivering genetic medicines, backed by real-world use in patients. Things like which fats they are made of, their shape at the molecular level, how ingredients mix, and how they are built, matter a lot. This review attempts to take a close look at how different components, such as ionizable lipids, auxiliary lipids (DSPC, DOPE), cholesterol, and PEG-based lipids, affect the bioavailability of LNPs. It also focuses on key functions of LNPs, including packaging genetic material, escaping cellular traps, spreading in the body, and remaining active in the blood. New data show that lipids with the right handedness and highly sensitive chiroptical quality control can sharpen delivery accuracy and boost transport rates, turning stereochemistry into a practical design knob. Rather than simply listing results, we examine real-world examples that are already used to regulate gene expression, enhance mRNA expression, splenic targeting, and show great potential for gene repair, protein replacement, and DNA base-editing applications. Also, recent advances in AI-based designs for LNPs that take molecular shape into account and help speed up modifications to lipid arrangements and mixture configurations are highlighted. In summary, this paper presents a practical and scientific blueprint to support smarter production of advanced LNPs used in genetic medicine, addressing existing obstacles, balanced with future opportunities. Full article

Small interfering RNAs (siRNAs) provide strong therapeutic potential due to their efficient gene-silencing properties; however, their instability limits clinical application. Nanoparticle carriers may overcome this problem; in particular, magnetic nanoparticles show great promise as they can be directed to the target sites by external magnetic fields, thus improving delivery efficiency and reducing off-target effects. In addition, magnetic nanoparticles offer a novel nanoplatform for theranostic applications, integrating siRNA delivery with magnetic resonance imaging and magnetic hyperthermia for synergistic diagnostic and therapeutic advantages. The present work reports the development of a novel platform based on biomimetic magnetic nanoparticles made of Fe(II)/Fe(III)-doped apatite (FeHA) nucleated and grown in the presence of cherry and pomegranate leaf extracts to enhance the colloidal stability and make it suitable for nucleic acid delivery under the guidance of magnetic fields. This approach allowed the obtention of FeHA suspension with increased negative zeta potential leading to very good stability. In addition, the functionalization with natural extracts conferred antioxidant properties also favoring the maintenance of the Fe(III)/Fe(II) ratio in the apatitic structure, inducing the superparamagnetic properties. To evaluate the delivery capability of the system, a model GAPDH-targeting siRNA molecule was employed. Its interaction with the nanoplatform was characterized by assessing loading capacity and release kinetics, which were further interpreted using mathematical modeling to elucidate the underlying release mechanisms. Full article

Background/Objectives: The design of scaffolds that mimic the extracellular matrix has gained increasing attention in regenerative medicine. This study aims to develop and characterize electrospun nanofibrous scaffolds based on pullulan blended with either gelatin or gliadin and doped with selenium nanoparticles (Se NPs), to assess the influence of protein type and Se NP doping on scaffold performance and regenerative potential. Methods: Se NPs were synthesized via redox reaction and stabilized using pullulan. Electrospun scaffolds were then prepared by blending pullulan-stabilized Se NPs with either gelatin or gliadin. The resulting fibers were characterized using a multidisciplinary approach, including physicochemical (morphology, fiber dimension, swelling capacity, surface zeta potential, mechanical properties) and preclinical properties (antioxidant properties, fibroblast adhesion and proliferation, collagen expression). Results: Protein type influenced fiber morphology and dimensions, as well as mechanical behavior, with gelatin-based scaffolds demonstrating smaller fiber diameters and higher mechanical properties. The doping with Se NPs enhanced scaffold antioxidant properties without affecting fiber formation. Moreover, all scaffolds supported fibroblast proliferation, but those containing Se NPs showed enhanced modulation of ECM gene expression. Conclusions: The results show that scaffolds doped with Se NPs exhibited superior performance compared to the undoped counterparts, offering promising platforms for chronic wound reparation. Full article

Erythropoietin (EPO) is a glycoprotein hormone essential for red blood cell production and a cornerstone therapy for anemia, particularly in chronic kidney disease. Beyond hematopoiesis, EPO exerts pleiotropic effects on metabolism, neuroprotection, and tissue regeneration. This review summarizes current insights into the molecular mechanisms, pharmacokinetics, and clinical applications of recombinant human EPO (rHuEPO) and its analogs, with emphasis on personalized therapeutic strategies. Emerging evidence highlights both therapeutic opportunities and risks, including resistance, cardiovascular complications, and misuse in sports doping. Advances in detection methods, pharmacogenomics, and the development of novel agents such as HIF-prolyl hydroxylase inhibitors are discussed, underscoring the expanding role of EPO in precision medicine. Full article

Small interfering RNAs (siRNAs) are particularly attractive among the frontier drugs due to their high specificity of action, activity on disease-inducing genes, and small molecular weight, thus being one of the most studied agents for gene therapy. However, siRNAs are prone to fast enzymatic degradation in the bloodstream, as well as other limitations that challenge their clinical translation. Nanoparticle (NP) delivery of siRNA has been proposed as a potential solution, overcoming their intrinsic limitations. In this regard, the siRNA delivery by magnetic nanoparticles is of particular interest because, being susceptible to external magnetic fields, it may be guided remotely, maximizing transfection efficiency and minimizing side effects. In addition, magnetic NPs would also allow a theranostic combination of drug delivery, magnetic resonance imaging, and hyperthermia. In this work we have studied the uptake of a model therapeutic siRNA by iron-doped hydroxyapatite nanoparticles (FeHA NPs), which are known to have excellent biocompatibility and magnetic susceptibility. We discovered that FeHA NPs stabilized by citrate (Cit-FeHA NPs) uptake siRNA by adsorption quickly and with high efficiency (ca. 90%) without altering nanoparticles physicochemical properties or colloidal stability. SiRNA-loaded Cit-FeHA NPs are able to slowly release their payload, with a sustained release of 45 days without siRNA degradation. Our work is therefore the preliminary validation of the suitability of FeHA NPs for magnetically guided delivery of therapeutic siRNAs. Full article

Cobalt is an essential trace element involved in key biological processes. It serves most notably as a component of vitamin B₁₂ (cobalamin) and a regulator of erythropoiesis. While cobalt deficiency can lead to disorders such as megaloblastic anemia, excess cobalt poses toxicological risks to the thyroid, cardiovascular, and hematopoietic systems. In recent years, cobalt ions (Co²⁺) have gained attention for their ability to mimic hypoxia and promote angiogenesis. This represents a crucial mechanism for tissue regeneration. Cobalt mediates this effect mainly by stabilizing hypoxia-inducible factor 1α (HIF-1α) under normoxic conditions, thereby upregulating angiogenic genes, including VEGF, FGF, and EPO. Experimental studies—from cell culture to animal models—have demonstrated cobalt-induced enhancement of endothelial proliferation, migration, and microvascular formation. Emerging evidence also indicates that Co²⁺-stimulated macrophages secrete integrin-β1-rich exosomes. These exosomes enhance endothelial motility and tubulogenesis independently of VEGF. Furthermore, cobalt-modified biomaterials have been developed to deliver cobalt ions in a controlled manner. Examples include cobalt-doped β-tricalcium phosphate or bioactive glasses. These materials support both angiogenesis and osteogenesis.This review summarizes current findings on cobalt’s role in angiogenesis. The emphasis is on its potential in cobalt-based biomaterials for tissue engineering and regenerative medicine. Full article

Background: In order to address complex scenarios in anti-doping science, especially in cases where an unintentional exposure of athletes to prohibited substances and a corresponding contamination of doping control samples at the collection event are argued, an understanding of tissue-specific drug metabolism is essential. Hence, in this study, the metabolic capacity of the seminal vesicle using in vitro assays was investigated. Methods: The aim was to assess whether selected doping-relevant substances—stanozolol, LGD-4033, GW1516, trimetazidine, and anastrozole—are metabolised in seminal vesicle cellular fractions (SV-S9) and how that metabolism compares to biotransformations induced by human liver S9 fractions (HL-S9). Liquid chromatography coupled to high-resolution/accurate mass spectrometry (LC HRAM MS) enabled the sensitive detection and identification of metabolites, revealing a limited metabolic activity of SV-S9. Results: For LGD-4033, GW1516, and trimetazidine, minor metabolic transformations were observed, whereas no metabolites of stanozolol or anastrozole were detected. Gene expression analysis using digital polymerase chain reaction (dPCR) confirmed transcripts of CYP2D6, CYP2E1, and CYP2C9 in SV-S9, though no enzymatic activity was detected. Gene expression and enzymatic activity in CYP3A4 and CYP1A2—major hepatic enzymes—were absent in SV-S9. Conclusions: Overall, these pilot study results suggest that the seminal vesicle has only a low capacity for xenobiotic metabolism, which translates into a limited role in the biotransformation of drugs and, hence, the metabolic pattern. Full article

In recent years, as gene therapy technology has rapidly developed, there has been growing concern that it could be misused by athletes as a means of doping. However, current testing methods for gene doping have a range of limitations and require further improvement. Furthermore, significant progress has been made in the fields of blood storage, next-generation sequencing (NGS), and LabDroid (experimental robots). Against this background, this study was implemented to develop a test method for gene doping using dried blood spot (DBS), NGS, and the LabDroid ”Maholo”. As a first step, recombinant adeno-associated virus containing the human erythropoietin gene (hEPO) was injected into mice to establish a gene doping model. Subsequently, DBS was created using whole blood. Maholo was used to extract DNA from the DBS and to create DNA libraries for NGS. NGS in combination with bioinformatic analysis clearly identified DNA fragments that provided definitive evidence of gene doping in the mouse model, which were absent in the control mouse. To the best of our knowledge, this is the first attempt to use a biological model of hEPO gene doping in conjunction with Maholo, NGS, and DBS. This method should facilitate the further development of gene doping tests. Full article

UV-cured methacrylated chitosan (MCHIT) hydrogels were achieved in the presence of silanised tellurium-doped silica bioactive glass (BG-Te-Sil) to produce an antimicrobial and osteoconductive scaffold for tissue engineering applications. Methacrylation of chitosan enabled efficient crosslinking, and the curing process was evaluated by means of Fourier-transform infrared spectroscopy (FTIR) and photorheology analyses. Compressive testing on crosslinked hydrogels showed that the silanised, bioactive, doped glass increased the hydrogel’s elastic modulus by up to 200% compared to unreinforced controls. Antibacterial assays against Staphylococcus aureus ATCC 43300 revealed a significant (p < 0.05) reduction in bacterial metabolic activity for hydrogels containing 50 wt% of the Te-doped bioactive glass. In vitro cytocompatibility with human bone-marrow mesenchymal stem cells demonstrated sustained viability and uniform distribution at 72 h (live/dead staining, AlamarBlue). Under H₂O₂-induced oxidative stress, reinforced hydrogels downregulated pro-inflammatory genes (TNF-α, IFN-γ, IL-1β, and PGES-2). These results suggest that the presence of the silanised bioactive glass can significantly enhance mechanical stability, antibacterial properties, and anti-inflammatory responses without affecting cytocompatibility, making these hydrogels promising for tissue engineering applications. Full article

Delayed or non-healing of bone defects in an aging, multi-morbid population is still a medical challenge. Current replacement materials, like autografts, are limited. Thus, artificial substitutes from biodegradable polymers and bioactive glasses (BGs) are promising alternatives. Here, novel cerium-doped mesoporous BG microparticles (Ce-MBGs) with different cerium content were included in photocrosslinkable, methacrylated gelatin (GelMA) for promoting cellular functions of human mesenchymal stem cells (hBMSCs). The composites were studied for intrinsic morphology and Ce-MBGs distribution by scanning electron microscopy (SEM) and energy-dispersive X-ray spectroscopy (EDX). They were gravimetrically analyzed for swelling and stability, compressive modulus via Microsquisher^® and bioactivity by Fluitest^® calcium assay and inductively coupled plasma-optical emission spectrometry (ICP-OES), also determining silicon and cerium ion release. Finally, seeding, proliferation, and differentiation of hBMSCs was investigated. Ce-MBGs were evenly distributed within composites. The latter displayed a concentration-dependent but cerium-independent decrease in swelling, while mechanical properties were comparable. A MBG type-dependent bioactivity was shown, while an enhanced osteogenic differentiation of hBMSCs was achieved for Ce-MBG-composites and related to different ion release profiles. These findings show their strong potential in promoting bone regeneration. Still, future work is required, e.g., analyzing the expression of osteogenic genes, providing further evidence for the composites’ osteogenic effect. Full article

Biological hydroxyapatite (BHA) has been extensively employed in alveolar socket preservation, yet its clinical application is often compromised by delayed bone healing triggered by macrophage-mediated pro-inflammatory responses. Building upon our previous work, in which we successfully incorporated fluorine into BHA to develop fluorinated biogenic hydroxyapatite (FBHA) with superior physicochemical and biological properties, this study systematically investigated the effects of fluorine doping on macrophage-mediated osteoimmunomodulation and socket bone healing. The synthesized FBHA was characterized using SEM, EDS, and fluoride ion release assays to confirm fluorine incorporation. In macrophage co-culture models, FBHA demonstrated significant advantages over BHA, effectively suppressing iNOS and TNFα gene expression, reducing NO release, and inhibiting phagocytic activity in M1 macrophages. RNAseq analysis revealed that the M1 phenotype suppression might be mediated through enhanced cellular antioxidant activity. Moreover, in macrophage-conditioned microenvironments, FBHA significantly upregulated osteogenic gene expression and ALP activity of pre-osteoblasts. In vivo experiments demonstrated FBHA’s superior performance in alveolar ridge preservation, especially in new bone formation and mineralization inside sockets. Fluorine doping significantly boosted socket bone healing via suppressing the inflammatory response of macrophages and enhancing osteogenic differentiation of pre-osteoblasts. These findings provide valuable insights into the development of next-generation biomaterials for alveolar socket preservation. Full article