Search Results (248)

Background: Corneal endothelial dysfunction continues to be a primary indication for corneal transplantation globally. Due to ongoing constraints in donor tissue availability and graft durability, artificial graft technologies are increasingly recognized as viable alternatives, particularly for eyes unsuitable for conventional allogeneic transplantation. Aim: This article examines the contemporary state of artificial corneal endothelial grafts, emphasizing technological advancements, incorporation into surgical procedures, and their developing function in meeting the unfulfilled requirements of endothelial keratoplasty. Methods: A comprehensive synthesis of recent preclinical and clinical literature was performed, concentrating on scaffold-based constructs, cell-seeded and acellular methodologies, biomaterial characteristics, and innovative surgical delivery techniques. The review highlights translational pathways and contrasts the initial outcomes of artificial and donor-derived endothelial grafts. Results: Advancements in regenerative biomaterials and cell culture systems have resulted in the development of functional endothelial substitutes. Engineered grafts, comprising decellularized stromal carriers, synthetic polymer matrices, and human cell-laden constructs, have demonstrated promising biocompatibility and functional results in preliminary trials. The integration of these constructs into methods akin to Descemet membrane endothelial keratoplasty (DMEK) has improved clinical viability, diminished immunologic risk, and shown potential for visual recovery. Conclusions: Artificial endothelial grafts signify a revolutionary advancement in corneal surgery, addressing donor shortages and expanding the applications of endothelial keratoplasty. Although additional clinical validation and regulatory processes are required, existing evidence indicates that these technologies may soon transform treatment protocols for corneal endothelial disease. Full article

Background/Objectives: Targeted cancer therapies increasingly rely on modulating specific cell death pathways and kinase signaling. Due to their structural versatility and potential to induce mechanistically distinct cytotoxic responses, benzoxazine–purine hybrids represent a promising scaffold for anticancer drug development. The objective of this study was to design and evaluate novel benzoxazine–purine derivatives for their antiproliferative activity and elucidate their underlying mechanisms of action. Methods: A series of benzoxazine–purine compounds was synthesized via a modular and efficient approach. The synthetic route involved a one-pot cyclization of substituted 2-aminophenols with epichlorohydrin, followed by tosylation and subsequent Mitsunobu coupling with halogenated purines. Their antiproliferative activity was assessed in MCF-7 (breast) and HCT-116 (colon) cancer cell lines using MTT assays. Selected compounds were evaluated further for kinase inhibition, effects on the cell cycle, membrane integrity (Annexin V/PI staining), ultrastructural changes (SEM), and caspase activation (Western blot). In silico ADMET profiling was also performed. Results: Compounds 9 and 12 exhibited the most potent antiproliferative activity, with low micromolar IC₅₀ values. Compound 12 showed dual HER2/JNK1 kinase inhibition and induced caspase-8-dependent pyroptosis-like cell death, characterized by membrane rupture and inflammatory features. In contrast, compound 8 lacked kinase inhibition and promoted S-phase arrest with apoptotic-like morphology. Both compounds demonstrated favorable physicochemical and ADMET profiles, including high intestinal absorption and an absence of mutagenicity. Conclusions: The rational design of benzoxazine–purine hybrids resulted in the discovery of compounds with distinct mechanisms of action. Compound 12 induces inflammatory cell death by modulating kinases, while compound 9 acts through a kinase-independent apoptotic pathway. These results underscore the therapeutic potential of scaffold-based diversification for developing targeted anticancer agents. Full article

Background: Periodontal regeneration has become a focal point in modern dental therapy, aiming to restore the form and function of lost periodontal structures. A literature search was conducted on the PubMed, Scopus, and Web of Science databases, focusing on studies published between 2000 and 2025 that addressed the clinical use of dental biomaterials in periodontal regeneration. Emphasis was placed on the use of bone grafts, guided tissue regeneration (GTR) membranes, enamel matrix derivatives, scaffolds, growth factors, and stem cell-based technologies. The review also outlines the limitations of current strategies, including unpredictable clinical responses, the rapid degradation of bioactive components, and variability in healing. Emerging directions, such as nanotechnology, gene-activated matrices, and 3D-printed scaffolds, are highlighted for their potential to improve predictability and personalization in periodontal therapy. This synthesis underscores both the progress and ongoing challenges in the field, emphasizing the need for continued research into material innovation and patient-specific solutions. Full article

Neurodegenerative diseases (NDDs) pose an immense global health burden, and developing effective treatments is hindered by the blood–brain barrier (BBB). Intrathecal (IT) administration of therapeutics directly into the cerebrospinal fluid (CSF) bypasses the BBB, offering a promising avenue for antisense oligonucleotides (ASOs), gene therapies, antibodies, and stem cells for these disorders. This review synthesizes the current landscape of IT therapies for Alzheimer’s disease, Parkinson’s disease, Huntington’s disease, and Amyotrophic Lateral Sclerosis based on the current literature and ClinicalTrials.gov. We highlight key trials and approaches, including the success of ASOs in spinal muscular atrophy and recent progress in other NDDs. However, the efficacy of these novel treatments is often constrained by the limitations of first-generation IT delivery systems, which struggle with uneven distribution, systemic leakage, and the demands of modern biologics. Drawing from recent analyses, we underscore the critical shortcomings of current devices and point out the innovations needed in shaping next-generation systems: subcutaneous access ports, CSF flow platforms, AI-driven adaptive dosing, nanoporous membranes, intrathecal pseudodelivery, and hydrogel scaffolds. We conclude by emphasizing the urgent need for these advanced IT drug delivery systems, alongside rigorous comparative assessments, cost–benefit analyses, and clear regulatory pathways to fully realize the potential of emerging CNS therapies and transform NDD management. Full article

Single-particle inductively coupled plasma mass spectrometry (spICP-MS) offers the unprecedented advantage of sensitive and selective detection of individual particles based on their constituent elements. It has been applied to the qualitative/quantitative evaluation of nonporous/mesoporous particles ranging from the nanoscale to the microscale and, recently, targeted proteins bound to particles. However, lipid membranes bound to particles have not been explored as potential targets for spICP-MS, despite its analytical potential. To address this, we investigated the applicability of spICP-MS for evaluating the binding states of two different types of lipid membranes (liposomes, i.e., phospholipid bilayer-based spherical vesicles, and nanodiscs comprising a disc-shaped phospholipid bilayer and membrane scaffold protein) to mesoporous silica microspheres (SBA24). The presence of bound liposomes and nanodiscs was confirmed using spICP-MS, which selectively monitored the derived P as a marker element. The presence of bound liposomes was confirmed by confocal laser Raman microscopy. Our findings demonstrate that spICP-MS can be used to qualitatively evaluate the binding states of lipid membranes to mesoporous SiO₂ microspheres. This method offers a new platform for evaluating the effectiveness of particles as carriers of biomolecules (lipid membranes) and provides valuable insights into biomedical research and quality control in related industries. Full article

Penicillin-binding proteins (PBPs) are essential enzymes involved in bacterial cell wall biosynthesis and represent the primary targets of β-lactam antibiotics. However, the efficacy of these agents is threatened by β-lactamase production and PBP alterations, prompting the search for alternative strategies. In this context, boronic acids, long established as potent inhibitors of serine β-lactamases (SBLs), have been proposed as scaffolds for PBP inhibition based on the shared structural and mechanistic features of these enzyme families. This perspective provides a literature-based survey with structural analysis to evaluate emerging evidence on the potential role of boronic acids as PBP-targeting agents, with a particular focus on peptidomimetic boronic acids, repurposed β-lactamase inhibitors, and novel scaffold architectures. While early work showed limited activity against low-molecular-mass PBPs, more recent compounds, particularly certain bicyclic boronates, have demonstrated potent binding and, in some cases, antibacterial activity. Structural analyses reveal diverse binding modes and underscore the role of conformational dynamics in modulating affinity. Despite these advances, significant challenges remain, including target selectivity, membrane permeability, and species-specific differences. Nevertheless, the direct inhibition of PBPs by boronic acids, while still in early development, may offer a viable complement or alternative to β-lactam therapy, warranting further exploration through structure-guided design and comprehensive biological evaluation. Here, we analyze the potential of boronic acid inhibitors (BAIs) to target PBP enzymes, considering their promise as non-β-lactam antimicrobial agents with possible clinical relevance. Full article

Background: The increasing prevalence of antibiotic-resistant bacterial strains highlights the urgent need for new membrane-targeting antimicrobial agents. Bisquaternary ammonium compounds (bisQACs) have attracted attention for their ability to disrupt bacterial membranes more effectively than monoquaternary analogs. Quinuclidine, known for its health-beneficial properties, has previously been explored for monoQAC derivatization, but studies using natural scaffolds to generate bisQACs remain limited. Methods: Here, we synthesized twelve novel quinuclidine-based bisQACs, systematically varying alkyl chain and linker lengths to investigate structure–activity relationships. Results: Several compounds, including 2(QC₁₆)₃, 2(QC₁₆)₄, 2(QC₁₄)₆, and 2(QC₁₆)₆, exhibited strong activity against Staphylococcus aureus (including MRSA), Listeria monocytogenes, and Escherichia coli, with 2(QC₁₆)₆ being the most potent (MICs 5–38 µM). While cytotoxicity was observed on human RPE1 and HEK293 cells, selectivity indices indicated a favorable therapeutic window relative to reference QACs. Conclusions: These compounds also inhibited biofilm formation and induced rapid bacterial killing through a membrane-disruptive mode of action. Molecular docking showed that alkyl chain and linker variations modulate binding to the QacR efflux regulator, revealing a lower potential for efflux-mediated resistance. Overall, quinuclidine-based bisQACs represent promising leads for potent, selectively active next-generation antimicrobials with a reduced likelihood of resistance development. Full article

Regenerative endodontics seeks to restore the vascularized pulp–dentin complex following conventional root canal therapy, yet reliable neovascularization within the constrained root canal remains a key challenge. This study investigates the development of an injectable, dual-curing hydrogel based on methacrylated decellularized amniotic membrane (dAM-MA) and compares its performance to a conventional gelatin methacryloyl (GelMA). The dAM-MA platform was designed for biphasic release, incorporating both free vascular endothelial growth factor (VEGF) for an initial burst and matrix-metalloproteinase-cleavable VEGF conjugates for sustained delivery. The dAM-MA hydrogel achieved shape-fidelity via thermal gelation at 37 °C and possessed tunable stiffness (0.5–7.8 kPa) after visible-light irradiation. While showing high cytocompatibility comparable to GelMA (>125% hDPSC viability), the dAM-MA platform markedly outperformed the control in promoting endothelial tube formation (up to 800 µm total length; 42 branch points at 96 h). The biphasic VEGF release from dAM-MA matched physiological injury kinetics, driving both early chemotaxis and late vessel maturation. These results demonstrate that dAM-MA hydrogels combine native extracellular matrix complexity with practical, dual-curing injectability and programmable VEGF kinetics, offering a promising scaffold for minimally invasive pulp–dentin regeneration. Full article

Valued for their nutritional content, eggs have recently gained attention as a versatile biomaterial owing to their biocompatibility, biodegradability, and unique structural and biochemical composition. This review highlights the biomedical potential of various egg components—eggshell, eggshell membrane, egg white, and egg yolk—and their applications in bone grafting, tissue engineering, wound healing, drug delivery, and biosensors. Eggshells serve as a natural, calcium-rich source for bone tissue engineering and regenerative medicine. The eggshell membrane, with its antimicrobial and structural properties, offers promise as a wound healing scaffold. Egg white, known for its gelation and film-forming capabilities, is utilized in hydrogel-based systems for drug delivery and biosensing. Egg yolk, rich in lipids and immunoglobulin Y (IgY) antibodies, is being explored for diagnostic and therapeutic applications. This review critically examines the advantages and limitations of each egg-derived component and outlines current research gaps, offering insights into future directions for the development of egg-based biomaterials in biomedical engineering. Full article

Background/Objectives: The clinical potential of antimicrobial peptides (AMPs) against dual threats like antimicrobial resistance (AMR) and cancer is often limited by their high host cell toxicity. Here, we focused on brevinin-2OS (B2OS), a novel peptide from the skin of Odorrana schmackeri with potent haemolytic activity. The objective was to study the structure–activity relationship and optimise the safety via targeted modifications. Methods: A dual-modification strategy involving C-terminal truncation and subsequent N-terminal D-amino acid substitution was employed. The bioactivities and safety profiles of the resulting analogues were evaluated using antimicrobial, haemolysis, and cytotoxicity assays. Result: Removal of the rana box in B2OS(1-22)-NH₂ substantially reduced haemolysis while maintaining bioactivities. Remarkably, the D-leucine substitution in [D-Leu²]B2OS(1-22)-NH₂ displayed a superior HC₅₀ value of 118.1 µM, representing a more than ten-fold improvement compared to its parent peptide (HC₅₀ of 10.44 µM). This optimised analogue also demonstrated faster bactericidal kinetics and enhanced membrane permeabilisation, leading to a greater than 22-fold improvement in its therapeutic index against Gram-positive bacteria. Conclusions: The C-terminal rana box is a primary determinant of toxicity rather than a requirement for activity in the B2OS scaffold. The engineered peptide [D-Leu²]B2OS(1-22)-NH₂ emerges as a promising lead compound, and this dual-modification strategy provides a powerful design principle for developing safer, more effective peptide-based therapeutics. Full article

Refractory full-thickness macular holes (rFTMHs) present a significant challenge in vitreoretinal surgery, with reported incidence rates of 4.2–11.2% following standard vitrectomy with internal limiting membrane (ILM) peeling and gas tamponade. Risk factors include large hole size (>400 µm), chronicity (>6 months), high myopia, incomplete ILM peeling, and post-operative noncompliance. Multiple surgical techniques exist, though comparative evidence remains limited. Current options include the inverted ILM flap technique, autologous ILM transplantation (free flap or plug), lens capsular flap transplantation (autologous or allogenic), preserved human amniotic membrane transplantation, macular subretinal fluid injection, macular fibrin plug with autologous platelet concentrates, and autologous retinal transplantation. Closure rates range from 57.1% to 100%, with selection depending on hole size, residual ILM, patient posturing ability, etc. For non-posturing patients, fibrin plugs are preferred. Residual ILM cases may benefit from extended peeling or flap techniques, while large holes often require scaffold-based (lens capsule, amniotic membrane) or fibrin plug approaches. Pseudophakic patients should avoid posterior capsular flaps due to lower success rates. Despite promising outcomes, the lack of randomized trials necessitates further research to establish evidence-based guidelines. Personalized surgical planning, considering anatomical and functional goals, remains crucial in optimizing visual recovery in rFTMHs. Full article

Electrospun nanofiber membranes (ESNFMs) are exceptional biomaterials for tissue engineering, closely mimicking the native extracellular matrix. However, their inherent fragility poses significant handling, processing, and integration challenges, limiting their widespread application in advanced 3D tissue models and biofabricated devices. This study introduces a novel and on-mat framing technique utilizing extrusion-based printing of a UV-curable biocompatible resin (Biotough D90 MF) to create rigid, integrated support structures directly on chitosan–polyethylene oxide (PEO) ESNFMs. We demonstrate fabrication of these circular frames via precise 3D printing and a simpler manual stamping method, achieving robust mechanical stabilization that enables routine laboratory manipulation without membrane damage. The resulting framed ESNFMs maintain structural integrity during subsequent processing and exhibit excellent biocompatibility in standardized extract assays (116.5 ± 12.2% normalized cellular response with optimized processing) and acceptable performance in direct contact evaluations (up to 78.2 ± 32.4% viability in the optimal configuration). Temporal assessment revealed characteristic cellular adaptation dynamics on nanofiber substrates, emphasizing the importance of extended evaluation periods for accurate biocompatibility determination of three-dimensional scaffolds. This innovative biofabrication approach overcomes critical limitations of previous handling methods, transforming delicate ESNFMs into robust, easy-to-use components for reliable integration into complex cell culture applications, barrier tissue models, and engineered systems. Full article

Background/Objectives: Truncating mutations in PALB2, a critical component of the BRCA1-PALB2-BRCA2 homologous recombination repair complex, are associated with increased risk and aggressiveness of breast cancer. The consequences of PALB2 truncation on the expression, localization, and functional dynamics of the scaffold protein IQGAP1 were investigated in this study based on two cases of truncated PALB2 human breast invasive ductal carcinoma (IDC), specifically, c.1240C>T (p.Arg414*) and c.2257C>T (p.Arg753*). Methods: Using confocal microscopy, we examined co-expression patterns of IQGAP1 with PALB2, PCNA, CK7, and β-tubulin in tumor tissues from both control cancer and PALB2-mutated cases. Results: In PALB2-truncated tumors, IQGAP1 exhibited enhanced peripheral and plasma membrane localization with elevated co-localization levels compared to controls, suggesting altered cytoskeletal organization. PALB2 truncation increased nuclear and cytoplasmic N-terminal PALB2 immunoreactivity, indicating the presence of truncated isoforms disrupting the homologous recombination repair system. Co-expression analyses with PCNA revealed an inverse expression pattern between IQGAP1 and proliferation markers, suggesting S-phase cell cycle-dependent heterogeneity. Furthermore, the loss of IQGAP1 dominance over CK7 and β-tubulin in mutant tumors, along with persistent intercellular spacing, implied a loss of cell–cell cohesion and the acquisition of invasive traits. Conclusions: These data support a model where PALB2 truncation triggers a reorganization of IQGAP1 that disrupts its canonical structural functions and facilitates tumor progression via enhanced motility and impaired cell–cell interaction. IQGAP1 thus serves as both a functional effector and potential biomarker in PALB2-mutated IDC, opening novel paths for diagnosis and targeted therapeutic intervention. Full article

The extracellular matrix (ECM) is a collagen-based scaffold that provides structural support and regulates nutrient transport and cell signaling. ECM homeostasis depends on a dynamic balance between synthesis and degradation, the latter being primarily mediated by matrix metalloproteinases (MMPs). These enzymes are secreted as pro-forms and require activation to degrade ECM components. Their activity is modulated by tissue inhibitors of metalloproteinases (TIMPs). Aging disrupts this balance, leading to the accumulation of oxidized, cross-linked, and denatured matrix proteins, thereby impairing ECM function. Bruch’s membrane, a penta-laminated ECM structure in the eye, plays a critical role in supporting photoreceptor and retinal pigment epithelium (RPE) health. Its age-related thickening and decreased permeability are associated with impaired nutrient delivery and waste removal, contributing to the pathogenesis of age-related macular degeneration (AMD). In AMD, MMP dysfunction is characterized by the reduced activation and sequestration of MMPs, which further limits matrix turnover. This narrative review explores the structural and functional changes in Bruch’s membrane with aging, the role of MMPs in ECM degradation, and the relevance of these processes to AMD pathophysiology, highlighting emerging regulatory mechanisms and potential therapeutic targets. Full article

Thiophene derivatives are particularly attractive for application in drug development for their versatile pharmacological properties. We synthesized a series of four compounds with thiophene carboxamide as a scaffold. The structures were established based on HR-MS and 1D- and 2D-NMR. The purity of the compounds was established to be greater than 92% by thin-layer chromatography and NMR. The cytotoxic effects of the newly synthesized compounds were evaluated against the normal HaCaT cell line and A375, HT-29, and MCF-7 cancer cell lines. The cytotoxic assessment revealed that two compounds exhibit a significant cytotoxic effect on all cancer cell lines. To investigate their potential underlying mechanisms of action, several tests were performed: immunofluorescence imaging, caspase-3/7 assay, mitochondrial membrane potential (JC-1) assay, and 2′,7′–dichlorofluorescein diacetate (DCFDA) assay. MB-D2 proved to be the most cytotoxic and effective in terms of caspase 3/7 activation, mitochondrial depolarization and decrease in ROS production; these effects did not occur in normal HaCaT cells, revealing that MB-D2 has a high selectivity against A375 cancer cells. Full article