Search Results (1,151)

Background: Synthetic vascular scaffolds often exhibit limited mechanical performance and low hydrophilicity, which compromise early vascular integration and increase susceptibility to bacterial colonization. This study developed 3D-printed scaffolds based on poly(L-co-D,L-lactide)–poly(trimethylene carbonate) (PLDLA–TMC) with polyethylene glycol 400 (PEG) to modulate mechanical and interfacial properties and coated with poly(hexamethylene biguanide) (PHMB) to confer antibacterial activity. Methods: PLDLA–TMC scaffolds modified with PEG 400 and coated with PHMB were prepared and systematically characterized to assess their structural, thermal, mechanical, and antimicrobial properties. PHMB coatings (3%, 6%, and 12% w/w in hydroxypropyl methylcellulose, HPMC) were applied and evaluated for drug release, cytotoxicity, and activity against Staphylococcus aureus. Biocompatibility was tested in an endothelial cell and myoblast co-culture. Results: Incorporation of 2% PEG increased the tensile strength from 0.14 ± 0.10 MPa for scaffolds containing 0.5% PEG to 0.79 ± 0.12 MPa and promotes a more elastic scaffold behavior. PHMB at 12% caused cytotoxicity (7.70 ± 0.37% cell viability). The 3% PHMB coating produced a 12.5 ± 0.1 mm inhibition zone but exhibited burst release within 1 h, whereas the 6% coating maintained cell viability (72.95 ± 1.10%), produced a 13.1 ± 0.2 mm inhibition zone, and provided sustained antimicrobial release over 7 days. Scaffolds supported organized adhesion and proliferation of endothelial cells and myoblasts. Conclusions: 3D-printed PLDLA–TMC scaffolds containing 2% PEG and coated with 6% PHMB combined improved mechanical performance, sustained antimicrobial release, antibacterial activity, and biocompatibility in an in vitro vascular model. Full article

Polymer-based bioactive composites are one of the most rapidly advancing areas in contemporary regenerative medicine. This review aims to identify major trends and knowledge gaps in the development of bioactive polymer composites and examine their translational relevance from a materials design perspective, with a specific focus on synthetic thermoplastic polymer matrices suitable for load-bearing bone scaffold applications and filament-based additive manufacturing. A total of 546 publications spanning 2016–2025 were screened, with 106 selected according to predefined relevance criteria. Bibliometric and content analyses were performed to delineate the primary research trajectories of bioactive composite materials. The results revealed that the majority of studies focused on composites comprising synthetic aliphatic polyesters, primarily polylactic acid (PLA) or polycaprolactone (PCL), reinforced with hydroxyapatite (HA) or bioactive glass (BG), which confer osteoconductivity but rarely achieve multifunctionality. Antimicrobial agents, ion-releasing components, and naturally derived bioactive molecules—associated with biointeractive functionalities and reported effects related to osteogenesis, angiogenesis, and immune modulation—are significantly underrepresented. Fewer than 20% of the investigated studies include in vivo validation, underscoring considerable scope for further preclinical and translational research. This work consolidates current trends in synthetic bioactive polymer composite design and identifies critical directions for future research. The findings of this review provide a structured framework to support the selection of composite fabrication and modification strategies, functional additives, and targeted biological functionalities for next-generation, load-bearing bone tissue engineering materials. Full article

Phorbazoles are bioactive marine alkaloids whose development is hampered by limited supply. We report a concise synthesis of the deschloro-phorbazole core via an optimized iodine-catalyzed oxazole annulation (56% yield). This route enabled efficient access to the scaffold and the preparation of analog B1. B1 showed nanomolar cytotoxicity (IC₅₀ = 0.04 µM) against MV4-11 leukemia cells by inducing G0/G1 arrest (via cyclin D1/CDK6 downregulation) and apoptosis. As a multi-kinase inhibitor, B1 also potently inhibited endothelial network formation and migration, demonstrating anti-angiogenic activity. This work provides an efficient synthetic strategy and identifies B1 as a promising dual-function anticancer lead compound. Full article

Quinolines are key heterocyclic motifs with broad utility in pharmaceuticals, agrochemicals, and materials science. The development of efficient and sustainable synthetic routes to access structurally diverse quinolines remains an important goal in organic chemistry. This review focuses on the recent advances in palladium-catalyzed strategies for quinoline synthesis, emphasizing oxidative and tandem annulation methods. Reactions are categorized by substitution patterns on the quinoline scaffold—namely 2-aryl, 4-substituted, 2,3-, 2,4- and 3,4-disubstituted, 2,3,4-trisubstituted, and annulated derivatives—to facilitate mechanistic comparisons and highlight structural scope. Together, the reviewed strategies showcase the range of mechanistic possibilities available for constructing quinoline scaffolds via palladium catalysis. Overall, these Pd-catalyzed approaches offer powerful and versatile tools for the synthesis of complex quinoline frameworks, providing valuable alternatives to classical heterocycle forming reactions. Full article

Emerging from millions of years of evolutionary optimization, Natural products (NPs) remain unique, unparalleled sources of bioactive scaffolds. Unlike synthetic molecules engineered around single therapeutic targets, NPs often exhibit multi-target, system-level bioactivity, aligned with the principles of network pharmacology, which modulates pathways in a coordinated, non-disruptive manner. This approach reduces resistance, buffers compensatory feedback loops, and enhances therapeutic resilience. Fungal endophytes represent one of the most chemically diverse and biologically sophisticated NP reservoirs known, producing polyketides, alkaloids, terpenoids, and peptides with intricate three-dimensional architectures and emergent bioactivity patterns that remain exceptionally difficult to design de novo. Advances in artificial intelligence (AI), machine learning, deep learning, and multi-omics integration have redefined the discovery landscape, transforming previously intractable fungal metabolomes and cryptic biosynthetic gene clusters (BGCs) into tractable, predictable, and engineerable systems. AI accelerates genome mining, metabolomic annotation, BGC-metabolite linking, structure prediction, and activation of silent pathways. Generative AI and diffusion models now enable de novo design of NP-inspired scaffolds while preserving biosynthetic feasibility, opening new opportunities for direct evolution, pathway refactoring, and precision biomanufacturing. This review synthesizes the chemical and biosynthetic diversity of major NP classes from fungal endophytes and maps them onto the rapidly expanding ecosystem of AI-driven tools. We outline how AI transforms NP discovery from empirical screening into a predictive, hypothesis-driven discipline with direct industrial implications for drug discovery and synthetic biology. By coupling evolutionarily refined chemistry with modern computational intelligence, the field is poised for a new era in which natural-product leads are not only rediscovered but systematically expanded, engineered, and industrialized to address urgent biomedical and sustainability challenges. Full article

Temporomandibular joint (TMJ) disorders represent chronic degenerative musculoskeletal conditions with a high prevalence in the general population and limited regenerative treatment options. Owing to the insufficient efficacy of current conservative and surgical therapies, there is a growing clinical need for biologically based regenerative approaches. Tissue engineering (TE), particularly scaffold-based strategies, has emerged as a promising avenue for TMJ regeneration. This systematic review analyzed preclinical in vivo studies investigating scaffold-based interventions for TMJ disc and osteochondral repair. A structured literature search of PubMed and Scopus databases identified 39 eligible studies. Extracted data included scaffold composition, use of cellular and bioactive components, animal models, and reported histological, radiological, and functional outcomes. Natural scaffolds, such as decellularized extracellular matrix and collagen-based hydrogels, demonstrated favorable biocompatibility and support for fibrocartilaginous regeneration, whereas synthetic materials including polycaprolactone, poly (lactic-co-glycolic acid), and polyvinyl alcohol provided superior mechanical stability and structural tunability. Cells were used in 17/39 studies (43%); quantitative improvements were variably reported across these studies. Bioactive molecule delivery, including transforming growth factor-β, histatin-1, and platelet-rich plasma, further enhanced tissue regeneration, while emerging drug- and gene-delivery approaches showed potential for modulating local inflammation. Despite encouraging results, the reviewed studies exhibited substantial heterogeneity in experimental design, outcome measures, and animal models, limiting direct comparison and translational interpretation. Scaffold-based approaches show preclinical promise but heterogeneity in design and incomplete quantitative reporting limit definitive conclusions. Future research should emphasize standardized methodologies, long-term functional evaluation, and the use of clinically relevant large-animal models to facilitate translation toward clinical application. However, functional and biomechanical outcomes were inconsistently reported and rarely standardized, preventing robust conclusions regarding the relationship between structural regeneration and restoration of TMJ function. Full article

Reliable vascular access remains a major clinical challenge for hemodialysis patients, as expanded polytetrafluoroethylene (PTFE) grafts exhibit poor patency and frequent complications driven by thrombosis and neointimal hyperplasia. Tissue-engineered vascular grafts offer a regenerative alternative but often lack the mechanical resilience required for high-flow arteriovenous (AV) environments. Here, we developed a reinforced, biofunctionalized coaxial electrospun graft comprising a poly(ε-caprolactone) mechanical core and a norbornene-functionalized poly(ethylene glycol) sheath incorporating pro-endothelialization cues. Circumferential PTFE rings were added to improve kink resistance. Grafts were implanted in a porcine AV configuration that recapitulates clinical hemodynamic conditions. Mechanical characterization included compliance, burst pressure, and kink resistance; host remodeling was assessed using histology, immunofluorescence, and multiphoton imaging at 4 weeks. Ring-reinforced electrospun grafts demonstrated a kink radius of 0.187 cm, compliance of 1.04 ± 0.29%/100 mmHg, and burst pressure of 1505 ± 565 mmHg, values all comparable to Gore-Tex PTFE and within industrial performance standards. In vivo, the electrospun grafts showed extensive host cell infiltration, collagen deposition, and formation of smooth muscle-like tissue, whereas PTFE controls remained largely acellular. Immunofluorescence confirmed intramural α-SMA⁺ and CD31⁺ cell populations, and multiphoton microscopy revealed significantly greater collagen and elastin content compared with PTFE (p < 0.05). Collectively, these findings demonstrate that the reinforced electrospun graft maintains mechanical integrity under physiological AV loading while supporting in situ endothelialization and extracellular matrix remodeling in a clinically relevant, large animal model. This work provides one of the first demonstrations of functional tissue regeneration within a fully synthetic, acellular scaffold in a porcine hemodialysis model and advances the translational development of durable, regenerative vascular access grafts that couple mechanical resilience with bioactive healing capacity. Full article

This research investigates the effects of corona plasma treatment on the mechanical properties of jute/epoxy-reinforced composites, particularly within biomedical application contexts. Plant Fibre Composites (PFCs) are attractive for medical devices and scaffolds due to their environmental friendliness, renewability, cost-effectiveness, low density, and high specific strength. However, their applications are often constrained by inferior mechanical performance arising from poor bonding between the plant fibre used as the reinforcement and the synthetic resin or polymer serving as the matrix. This study addresses the challenge of improving the weak interfacial bonding between plant fibre and synthetic resin in a 2/2 twill-weave-woven jute/epoxy composite material. The surface of the jute fibre is modified for better adhesion with the epoxy resin through plasma treatment, which exposes the jute fibre to controlled plasma energy and utilises dry air (plasma only), argon (Ar) (argon gas with plasma), and nitrogen (N₂) (nitrogen gas with plasma) at two different distances (25 mm and 35 mm) between the plasma nozzle and the fibre surface. In this context, “equilibrium” refers to the optimal combination of plasma power, treatment distance, and gas environment that collectively determines the degree of fibre surface modification. The results indicate that all plasma treatments improve the interlaminar shear strength in comparison to untreated samples, with treatments at 35 mm using N₂ gas showing a 35.4% increase in shear strength. Conversely, plasma treatment using dry air at 25 mm yields an 18.3% increase in tensile strength and a 35.7% increase in Young’s modulus. These findings highlight the importance of achieving an appropriate equilibrium among plasma intensity, treatment distance, and fibre–plasma interaction conditions to maximise the effectiveness of plasma treatment for jute/epoxy composites. This research advances sustainable innovation in biomedical materials, underscoring the potential for improved mechanical properties in environmentally friendly fibre-reinforced composites. Full article

Hydrogels are 3D networks of hydrophilic crosslinked polymers, which are synthesized from synthetic or natural sources such as chitosan and alginic acid derived from shrimp shell and brown seaweed, respectively. These materials exhibit biodegradability, biocompatibility, and non-cytotoxic properties to be used as scaffolds for tissue engineering applications. In this study, four types of alginic acid hydrogels were chemically synthesized using spermidine as a crosslinking agent with concentrations ranging from 5% (w/w) to 100% (w/w). The results of scanning electron microscopy (SEM) revealed a small average pore size (≤5 μm), while electrospray ionization mass spectrometry (ESI-MASS) and Fourier transform infrared spectroscopy (FT-IR) showed the characteristic vibrations and formed bonds between alginic acid and spermidine, respectively. Finally, the alginic acid hydrogels demonstrated potential ability for tissue regeneration treatments. Full article

The recent development in polymer science has gone beyond the traditional linear and randomly functionalizable macromolecules to the architected polymer systems, which integrate modular synthesis and dynamic responsiveness. Although the literature related to polymer synthesis and stimuli-responsive materials and applications is widely discussed, it is common to review the aspects independently, restricting a complete picture of how architectural modularity controls adaptive performance. This gap is filled in this review with an integrated framework of relating modular polymer synthesis, stimuli-responsive design, and application-oriented functionality in a single coherent design philosophy. The scientific novelty of this review is that the focus on modular polymers is not only on synthetic constructs, but is a programmable functional scaffold where the structural precision is the direct determinant of responsiveness, multifunctionality, and performance. Controlled polymerization and post-polymerization modification regimes are mentioned to be tools that allow precise positioning of functional modules, and this allows polymers to respond in predictable ways to environmental stimuli like pH, temperature, light, redox conditions, etc. In addition, the review identifies the role of a synergistic combination of various responsive modules in the emergence of behaviours that would not be reached in conventional polymer systems. This review offers a coherent viewpoint on the future of functional polymers of the next generation by bringing together synthetic approaches to nano-responsive behaviour and real-world technologies, such as drug delivery, self-healing surfaces, adaptive surfaces, and biosensing surfaces. The framework in the present paper provides a logical route towards the development of environmentally friendly, multifunctional, and adjustable polymer structures. Full article

This study explores crude oil as a chemically and structurally heterogeneous system with potential pharmaceutical relevance beyond its established roles as an energy and feedstock resource. Recent advances in analytical technologies have enabled the detailed characterization of crude oil constituents at the molecular level, thereby linking structural features to physicochemical properties and possible biological activities. The presented analysis outlines the rationale, methodological considerations, and future research directions for integrating crude oil molecular motifs into the pharmaceutical chemical space. Beyond its conventional role as an industrial and energy resource, crude oil may also hold promise for drug discovery. This study seeks to provide a conceptual framework for reconsidering crude oil as a reservoir of pharmacologically relevant scaffolds and to outline methodological approaches for their systematic assessment. Its rigid sp³-rich frameworks, together with sterane/hopane biomarkers, porphyrins, and functional aromatics, structurally overlap with established therapeutic classes and are naturally present in crude oil in suitable abundance, offering opportunities to reduce synthetic effort and expand the chemical space accessible to drug discovery. Advances in petroleomics and in silico methodologies now enable petroleum-derived constituents to be characterized in terms of drug-likeness, bioactivity, and toxicity, providing a framework to reconsider crude oil as an unconventional but analytically and computationally tractable resource for pharmaceutical research. Full article

The indole scaffold represents a privileged structural motif in medicinal chemistry, celebrated for its remarkable chemical versatility, biological ubiquity, and clinical relevance. This review provides a comprehensive analysis of the recent research on the indole nucleus, emphasizing its physicochemical properties, reactivity patterns, and capacity to interact with a wide array of biological targets. Found in key endogenous compounds such as serotonin and melatonin, indole serves as a cornerstone in neurochemical signaling, circadian regulation, and chrono-metabolic homeostasis. Beyond its physiological roles, synthetic indole derivatives have shown extensive therapeutic potential across diverse domains, including oncology, infectious diseases, neurodegenerative disorders, immunomodulation, and metabolic syndromes. The review explores structure–activity relationships (SAR), pharmacokinetics, and the molecular mechanisms by which indole-based compounds exert their tremendous effects, that are ranging from enzyme inhibition to receptor modulation. Special focus is given to current clinical applications and emerging strategies for enhancing drug specificity, bioavailability, and safety through indolic frameworks. Additionally, we highlight the translational potential of indole-containing molecules in personalized medicine, underscoring opportunities for future drug discovery. By integrating insights from medicinal chemistry, biochemistry, pharmacology, and clinical science, this review affirms the indole ring’s enduring value as a central scaffold in therapeutic innovation. Full article

The balance of alveolar macrophage (AM) polarization is severely disrupted in chronic inflammatory diseases like bronchiectasis, where a persistent pro-inflammatory (M1) phenotype perpetuates inflammation. To address this, we developed a high-throughput platform using a series of synthetic glycoligands (L1-L5) on a polyethyleneimine (PEI) scaffold. These ligands, which have varying affinities for macrophage lectin-like receptors, were used for phenotypic “fingerprinting” of AM subpopulations from pediatric bronchiectasis patients and a healthy control. Analysis of bronchoalveolar lavage fluid (BALF) revealed a pathogenic, M1-dominant profile (55% M1) in patients, confirming a state of chronic inflammation, which starkly contrasted with the quiescent, M0-dominant profile in the healthy control. We then leveraged this platform for targeted immunomodulation, using a drug-ligand conjugate to steer the dysregulated macrophage population toward a healthy state. The most potent conjugate, Dox-L5, dramatically suppressed the pathogenic M1 population (from 55% to 16%). This M1 suppression was accompanied by a significant shift toward the M2a (tissue-repair) phenotype and the emergence of a quiescent M0-like population, effectively remodeling the AM profile. This work validates a glycan-based platform for both diagnosing and correcting pathological macrophage imbalances. Our targeted approach offers a precise strategy to resolve chronic inflammation in bronchiectasis by suppressing M1 macrophages and promoting a pro-resolving M0/M2 phenotype, thereby restoring lung homeostasis. Full article

A series of novel granatane–triazole hybrid molecules was designed, synthesized, and evaluated as dual acetylcholinesterase (AChE) and β-secretase 1 (BACE1) inhibitors. The compounds were obtained through a convergent synthetic route involving azide formation, triazole construction via dipolar cycloaddition, and final coupling with a granatane scaffold to give a pseudopelletierine (3-granatanone) analogue. In vitro assays demonstrated that all target compounds inhibited both AChE and BACE1. Molecular docking and molecular dynamics simulations revealed stable interactions with key catalytic residues, suggesting distinct binding modes compared to reference ligands. QSAR-based pharmacokinetic predictions indicated favorable blood–brain barrier permeability and compliance with key drug-likeness filters. These findings identify granatane–triazole hybrids as promising multi-target directed ligand (MTDL) candidates with potential for further optimization in the search for new anti-Alzheimer therapeutics. Full article

Boron-dipyrromethene (BODIPY) dyes belong to a class of organoboron compounds that have become ubiquitous for researchers in areas of fluorescence imaging, photodynamic therapy, and optoelectronics. The intrinsic qualities of BODIPY dyes and their meso-modified structural analogs, Aza-BODIPY dyes, have propelled their recent increase in use in biomedical applications. The two scaffolds have high quantum yields, narrow absorption, and emission bandwidths with large Stokes’ shifts, and high photostability and thermal stability. Because their properties are independent of solvent polarity and dye functionality, they can be tuned to promote novel analytical methods, resulting in the adaptation of the physicochemical and spectral properties of the dyes. In this review of BODIPY and Aza-BODIPY scaffolds, we will summarize their spectral properties, synthetic methods of preparation, and applications reported between 2014 and 2025. This review aims to summarize the advances in chemosensing, especially pH sensor development, and the advances in NIR-II window bioimaging probes. We hope that this succinct overview of Aza-BODIPY scaffolds will highlight their untapped potential, elucidating insights that may catalyze novel ideas in the physical organic realm of BODIPY. Full article