Search Results (3,140)

Ultrasound-responsive antibacterial therapies represent a cutting-edge approach to combating implant-associated infections, particularly advantageous because of ultrasound’s non-invasive nature, deep penetration, and ability to target infected areas. However, most previous studies have been devoted to ultrasound-responsive nanomaterials, hydrogels, and polymer systems. Research on ultrasound-responsive surfaces on titanium remains in its early stages and is extremely limited. This review primarily focuses on the design principles and construction strategies for ultrasound-responsive antibacterial surfaces on titanium-based implants, key factors affecting acoustic energy conversion efficiency, and the approaches to enhance antibacterial efficiencies. Based on acoustic energy conversion mechanisms and the primary factors responsible for bacterial killing, this review classifies antibacterial surfaces into sonothermal surfaces, sonodynamic surfaces, and multimodal combined surfaces. Moreover, this review discusses perspectives and challenges regarding biocompatibility, long-term antibacterial activity after implantation, and future clinical translation. Full article

Resveratrol (RSV) is a naturally occurring polyphenol with well-documented antioxidant, anti-inflammatory, antimicrobial, photoprotective, wound-healing, depigmenting, and anticancer properties, making it an attractive candidate for dermocosmetic and dermatological applications. However, its clinical translation into effective topical products remains limited by poor aqueous solubility, chemical instability, photoisomerization, rapid cutaneous metabolism, and restricted skin penetration, all of which compromise local bioavailability and therapeutic efficacy. This narrative review critically examines the molecular mechanisms underlying the cutaneous effects of RSV and discusses how its physicochemical and pharmacokinetic characteristics influence topical performance. Particular emphasis is placed on advanced delivery strategies developed to overcome these limitations, including lipid-based nanocarriers, polymeric nanoparticles (NPs), nanofibers, inorganic nanocarriers, microneedles, hydrogels, and other emerging delivery platforms. The mechanisms by which these systems improve RSV solubility, stability, controlled release, skin retention, and dermal penetration are critically evaluated together with their reported therapeutic outcomes. Although advanced delivery systems have consistently improved the topical performance of RSV in preclinical studies, clinical evidence remains limited. To date, only one published placebo-controlled clinical trial has specifically evaluated topical RSV as the active ingredient, and none of the advanced RSV-nanocarrier platforms discussed in this review has undergone clinical evaluation. Bridging this substantial translational gap will require not only further optimization of formulation design but also scalable manufacturing, rigorous clinical validation, and regulatory pathways capable of supporting the development of safe, effective and evidence-based next-generation dermocosmetic and dermatological products. Full article

Background and Objectives: The main neurodegenerative diseases (NDs)—Alzheimer’s disease (AD), Parkinson’s disease (PD), multiple sclerosis (MS), and amyotrophic lateral sclerosis (ALS)—represent a growing global health burden with no available disease-modifying therapies. Curcumin, a polyphenol from Curcuma longa, is a promising candidate owing to its pleiotropic antioxidant, anti-inflammatory, and neuroprotective profile observed mainly in preclinical models, but the poor oral bioavailability (<1%) and negligible BBB penetration (<0.1%) have substantially limited curcumin’s clinical translation. The objective of this work was to critically examine the therapeutic potential of curcumin in NDs, focusing on advanced drug delivery systems (DDSs) designed to overcome its pharmacokinetic barriers. Methods: This is a narrative, non-systematic review of PubMed/MEDLINE, Scopus, and Web of Science. The review is organized around five complementary thematic areas selected to span the full translational pipeline of curcumin in neurodegeneration, from mechanistic rationale to clinical applicability: (1) molecular mechanisms, addressing the pleiotropic activities that justify therapeutic interest; (2) pharmacokinetic barriers, the principal obstacle to clinical translation; (3) the evolution of drug delivery systems (DDSs), documenting the technological strategies developed to overcome these barriers; (4) disease-specific applications, evaluating the available evidence across the four main NDs; and (5) translational limitations, identifying the methodological and regulatory gaps that must be closed to enable clinical implementation. Results: Curcumin exhibits neuroprotective activity in preclinical models of the four NDs analysed, acting on six interconnected mechanisms and the gut–brain axis. Four generations of DDSs have been developed, from phytosomes and clinically used lipid dispersions (Meriva^®, BCM-95^®, Longvida^®, and Theracurmin^®) to fourth-generation systems (biomimetic nanoparticles, MOFs, microneedles, 3D scaffolds, hydrogels, and carbon dots) that substantially increase the bioavailability in preclinical studies. Combination strategies, such as curcumin with resveratrol and dutasteride, show preliminary clinical signals in ALS. However, clinical translation remains limited: over 80% of positive animal findings have not been replicated in humans, formulation characterization is frequently incomplete, and most trials lack CNS-exposure biomarkers. Importantly, most of the reported bioavailability claims are based on total curcumin measurements (parent aglycone plus its inactive Phase II conjugates) rather than the active aglycone alone, a methodological limitation that should be considered when interpreting the magnitude of the bioavailability improvements reported for novel formulations. Conclusions: Curcumin exhibits pleiotropic neuroprotective activity in preclinical models of AD, PD, MS, and ALS, mediated by interconnected antioxidant, anti-inflammatory, anti-amyloidogenic, mitochondrial, and gut–brain axis mechanisms. However, its poor systemic bioavailability (<1%), minimal blood–brain barrier penetration, and extensive first-pass metabolism have limited clinical translation. Advanced drug delivery systems (including lipid-based carriers (liposomes, solid lipid nanoparticles, and nanostructured lipid carriers), polymeric nanoparticles (PLGA and chitosan), and bioinspired vesicles (exosomes)) are essential in order to overcome these barriers. Nevertheless, the formulation heterogeneity, limited long-term safety data, and reliance on preclinical models remain major obstacles; a definitive clinical translation will therefore require well-characterized formulations validated in phase II/III trials with cerebrospinal fluid exposure biomarkers, the pharmacokinetic monitoring of active aglycone (rather than total curcumin including inactive conjugates), and adaptive trial designs in neurological populations. Full article

Cutaneous wound healing is governed by dynamically interacting mechanical, redox, and bioelectrical signals that regulate cell migration, inflammation, angiogenesis, extracellular-matrix remodeling, and tissue regeneration. Hydrogels are increasingly engineered to modulate these cues; however, most systems are still described through independently measured properties such as stiffness, antioxidant activity, and conductivity, without demonstrating functional coupling among them. This review examines regenerative hydrogels from a cross-domain perspective, integrating the biological basis of mechanotransduction, redox signaling, endogenous bioelectricity, and their molecular convergence with the network-level mechanisms that control hydrogel behavior. Particular emphasis is placed on dynamic crosslinking, viscoelastic relaxation, hydration, redox-active chemistry, ionic and electronic transport, conductive and piezoelectric phases, and degradation-dependent evolution of material function. A conceptual hierarchy is proposed to distinguish property coexistence, structural integration, directional transduction, and adaptive feedback, together with experimental criteria and quantitative approaches for evaluating coupling. Current evidence indicates that mechanoelectrical coupling is the most mature, whereas mechanoredox and redox–electrical interactions remain less systematically quantified. Moving beyond descriptive multifunctionality toward controllable cross-domain transduction may enable hydrogels to function as adaptive soft interfaces capable of responding to the evolving physicochemical conditions of cutaneous regeneration. Full article

The global proliferation of multidrug-resistant Pseudomonas aeruginosa stimulates the search for alternatives to conventional therapy. This study developed human serum albumin (HSA)-based hydrogels for the delivery of bacteriophage PA57. Matrices were fabricated via combined thermal- and ethanol-induced gelation. The release kinetic was dependent on protein concentration: 20% (w/v) HSA provided sustained release over 48 h, whereas 10–15% (w/v) HSA exhibited burst release effects. Combined systems effectively suppressed P. aeruginosa growth in vitro during the early and middle stages of incubation, maintaining low culture optical density for up to 28 h. Although late-stage bacterial regrowth was observed, the final bacterial load remained significantly lower than in the control. Furthermore, cytocompatibility assays with HaCaT keratinocytes and MRC-5 fibroblasts demonstrated high cell viability, confirming the safety of the hydrogel matrix for wound healing applications. These results demonstrate the promise of HSA-based hydrogels as a platform for localized phage therapy of infected wounds. Full article

Bacterial infection, biofilm formation, and the associated oxidative stress and persistent inflammation represent major obstacles to wound healing, tissue engineering, and implantable medical devices. Owing to their highly hydrated three-dimensional networks, favorable tissue compatibility, and versatile capacity for functional loading, hydrogels have been widely investigated for the treatment of infected wounds. This review systematically summarizes the major antibacterial mechanisms of hydrogels, including cationic contact-killing, chemical antibacterial activity mediated by metal ions and reactive halogen species, nanozyme-catalyzed reactions and bidirectional regulation of reactive oxygen species, as well as photothermal synergistic antibacterial therapy. Key design strategies are also discussed, including natural polymer-based matrices, multiple dynamic crosslinking, stimuli-responsive controlled release, three-dimensional printing, and spatial compartmentalization. In addition, recent advances in infection-microenvironment regulation, wet-interface adaptation, temporally coordinated tissue repair, and integrated diagnosis and therapy are highlighted. The field is currently shifting from single-mode bacterial eradication toward multistage tissue repair and intelligent theranostics. However, major challenges remain, including balancing antibacterial efficacy with biosafety, achieving reproducible manufacturing and sterilization-compatible formulations, maintaining functional stability during storage, and improving the clinical relevance and standardization of preclinical evaluation. In addition, most smart systems still lack quantitative coupling among pathological signals, therapeutic dosage, and treatment outcomes. Future studies should therefore integrate mechanistic design with manufacturing reproducibility, clinically relevant validation, and quantitative feedback regulation, thereby advancing antibacterial hydrogels from multifunctional proof-of-concept systems toward precise, controllable, and clinically translatable therapeutic platforms. Full article

Intrauterine adhesion (IUA) is a fibrotic disorder resulting from aberrant repair following injury to the endometrial basal layer, leading to menstrual abnormalities, infertility, recurrent miscarriage, and pregnancy complications. Although hysteroscopic adhesiolysis remains the primary clinical treatment, the rate of postoperative re–adhesion is still high, especially in patients with moderate–to–severe IUA. Moreover, mechanical separation alone is often insufficient to restore intact endometrial architecture and reproductive function. Hydrogels, with their hydrated three–dimensional networks, extracellular matrix (ECM)–mimicking properties, injectability, biodegradability, tissue adhesion, and tunable delivery capacity, have evolved from passive barrier materials into multifunctional therapeutic platforms capable of regulating the pathological microenvironment and promoting tissue regeneration. Recent advances in responsive, self–healing, adhesive, antioxidant, and bioactive cargo–loaded hydrogels have expanded their applications from preventing adhesion formation toward functional endometrial reconstruction. In this review, we summarize recent progress in hydrogel–based IUA therapy, focusing on material composition, structural design, functional modification, therapeutic mechanisms, and translational considerations. Particular emphasis is placed on disease–informed hydrogel engineering strategies that integrate the unique anatomical characteristics of the uterine cavity, injury–associated microenvironment, and dynamic stages of endometrial repair. This perspective provides insights into the development of next–generation hydrogel systems for preventing re–adhesion and restoring reproductive function. Full article

Methotrexate (MTX) remains central to the treatment of rheumatoid arthritis and several malignancies, yet its use is complicated by dose-dependent toxicity, variable oral exposure, photolability, and pH-dependent solubility. Cyclodextrins (CDs) can alter the molecular environment of MTX, but the literature often conflates true inclusion complexes with formulations in which CD merely forms part of a larger carrier. This review critically distinguishes direct MTX–CD complexes, dosage forms built from a preformed complex, CD-containing carriers without direct evidence of cavity occupancy, and covalent MTX–CD conjugates. Particular attention is given to binding stoichiometry, apparent association constants, guest orientation, preparation methods, and the evidence needed to establish inclusion. Both solution-state host–guest association and isolated solid products are considered; however, solid-state changes are treated as supportive evidence rather than as stand-alone proof of cyclodextrin cavity occupancy. Among the limited head-to-head comparisons of native cyclodextrins, β-CD generally showed more favorable MTX recognition than α- or γ-CD, although the magnitude of this difference is method- and condition-dependent. Complexation can improve dissolution, photostability, and oral or local delivery; however, greater solubilization does not necessarily enhance membrane transport. In carrageenan hydrogels, β-CD increased MTX loading and release while reducing membrane permeation, illustrating the importance of the equilibrium between complexed and freely permeating drug. The most promising systems remain preclinical. Progress toward translation will require clearer nomenclature, orthogonal structural characterization, mechanism-resolving controls, and standardized pharmacokinetic and safety studies. Full article

Background: The fibrous tumor extracellular matrix (ECM), driven by cancer-associated fibroblasts (CAFs), forms a physical barrier against drugs and immune cells, yet direct CAF elimination risks promoting metastasis. Methods: In this study, we developed a locally injectable hydrogel based on synergistic dynamic covalent crosslinking (imine and boronate ester bonds), enabling instant gelation, shear thinning, and dual-pH/ROS-responsive degradation. Two types of drug-loaded nanoparticles (NPs), coated with homotypic cell membranes, were incorporated into this hydrogel. In the acidic, reactive oxygen species (ROS)-rich tumor microenvironment (TME), the system responsively releases the antifibrotic drug SIS3 to reprogram CAFs while simultaneously delivering doxorubicin (DOX) specifically to tumor cells. Biological effects were evaluated in vitro using cell cultures and in vivo in mouse models. Results: This dynamic hydrogel-based co-delivery system effectively reprograms CAFs, reduces tumor mechanical stress, breaks the fibrotic barrier, and promotes the deep infiltration of chemotherapeutics and immune cells, thereby enhancing the efficacy of chemotherapy. Conclusions: This injectable pH/ROS-responsive dynamic covalent hydrogel, loaded with CAF- and cancer cell-targeting NPs, remodels the TME, enhances drug and immune cell penetration, and offers a promising biomaterial-based strategy for cervical cancer treatment. Full article

Background: Postpartum hypogalactia is a prevalent obstetric complication worldwide, closely associated with excessive oxidative stress and impaired antioxidant defense in mammary tissue. Current hormone-based therapies carry endocrine disruption risks, while natural antioxidant bioactive agents such as extracellular vesicles (EVs) are largely limited by rapid in vivo clearance and poor tissue retention. Methods: We constructed an injectable gelatin methacryloyl (GelMA) hydrogel system to encapsulate chemically induced mammary epithelial cell-derived EVs (CiMECs-EVs) and systematically evaluated their antioxidant and lactogenic activities via multi-omics analysis, cellular functional assays and a bromocriptine-induced murine hypogalactia model. Results: CiMECs-EVs induced a functional mammary epithelial-like phenotype in fibroblasts in a dose-dependent manner with functional cargo enriched in glutathione metabolism and redox-regulatory miRNAs. The GelMA matrix protected EV integrity and enabled sustained release, and the composite system significantly ameliorated mammary duct structure and lactation function in vivo with specific mammary tropism and no systemic toxicity, outperforming free EV treatment. Conclusions: This study presents a safe protein biomacromolecule-based antioxidant delivery platform that effectively restores mammary redox balance and antioxidant defenses, providing a promising non-hormonal therapeutic strategy for postpartum hypogalactia. Full article

Nanomaterials are increasingly expected to do more than transport a payload, yet added complexity is useful only when it resolves a rate-limiting diagnostic, transport, release, or monitoring problem. This review develops a function-first framework for precision diagnostics and drug delivery in which formation and processing are linked to nanoscale structure, material properties, demonstrated function, route-specific evidence, and translational value. The scope includes AI-assisted plasmonic and terahertz biosensing; biopolymer nanoparticles and hydrogel depots; barrier-directed nose-to-brain and systemic delivery; graphene and carbon nanotube interfaces; lipid nanoparticles for nucleic acid packaging and endosomal escape; nanoporous, magnetic, and plasmonic carriers; and closed-loop theranostic systems. A platform is treated as genuinely multifunctional only when at least two deliberately engineered functions are experimentally supported and either act on distinct rate-limiting steps or close a sensing–intervention–monitoring loop. This review therefore distinguishes total loading from bioavailable payload, cellular uptake from productive delivery, imaging labels from intact carrier fate, and nominal stimulus responsiveness from controlled release in response to a physiologically realistic trigger. Recent independent studies are used to broaden comparisons across material classes and to separate proof-of-concept performance from translational evidence. Artificial intelligence is considered in three distinct roles—sensor interpretation, formulation/material optimization, and prediction of in vivo behavior—with external validation and, where a model is intended to guide decisions, prospective testing treated as essential. The resulting framework emphasizes biological identity, route-specific safety, carrier-versus-payload tracking, critical quality attributes, manufacturing reproducibility, and a minimum-evidence roadmap from concept to product. Full article

In this study, beeswax (BW) and gelatin, soapwort root powder (SRP) were employed to create oleogel and hydrogel for bigel development, respectively. The study aimed to determine the potential utilization of SRP in the bigel system to create a novel fat replacer (bigel-based foamed emulsion) for mousse production. Bigels with 2% SRP showed a bicontinuous emulsion structure. The FTIR spectra of all the bigels exhibited no new peaks. Bigels had solid-like properties, given that no crossover point was present and G′ values were uniformly greater than G″ values. Hardness, gumminess, and chewiness were improved by increasing the bigel’s gelatin and SRP concentrations. A rise in the SRP ratio and gelatin content resulted in a higher overrun of bigel-based foamed emulsions. An increment in the SRP ratio resulted in enhanced thermal stability, with the exception of 9% G-2. The G′ values surpassed the G″ values, indicating that the mousse samples exhibited solid-like characteristics. From the prepared samples, 6% G-2 M was determined to be the closest to the control mousse in terms of hardness, springiness, cohesiveness, and gumminess values when comparing the bigel mousse samples with the control mousse sample (p > 0.05). The 6% G-2 M sample showed the lowest ΔE* value and was the closest sample to CM. Full article

Silk fibroin (SF)- and silk sericin (SS)-based antibacterial hydrogels are increasingly engineered as local antimicrobial platforms, yet cross-study interpretation is limited by inconsistent material reporting and by conflation of bacterial inhibition with tissue repair. We performed a structured evidence-mapping and critical synthesis of a frozen 2020–July 2026 corpus of 94 references. The original 46-record core map was re-audited at the original-article level: 43 full-text-verified, non-retracted primary studies were retained for detailed evidence grading, 2 records available only at abstract/database level were retained descriptively but not graded, and 1 subsequently retracted study was excluded from quantitative synthesis. Among the 43 graded studies, metal-ion/nanozyme/catalytic systems were most common (12/43, 27.9%), followed by release-mediated (11/43, 25.6%), multimodal (9/43, 20.9%), contact-active/anti-adhesive (6/43, 14.0%), and light-responsive systems (5/43, 11.6%). Sixteen studies (37.2%) used deliberately infected animal models, whereas only 4 (9.3%) reached a biofilm or adherent-bacteria-level endpoint in the graded map. Biological claim ceilings (C0–C5) are assessed independently from translation gates spanning material identity, reproducibility, mechanism, host safety, sterilization/storage, resistance, long-term fate, and deployment. Across mechanisms, SF and SS most often function as structural, interfacial, or transport-regulating matrices; direct silk-dependent bactericidal causality remains uncommon. The central translational deficit is failure to quantitatively link silk molecular identity and network architecture to antimicrobial exposure, bacterial killing, host selectivity, and long-term material fate. Full article

The sequential phases of tissue healing—inflammation, proliferation, and remodeling—demand distinct pharmacokinetic profiles that conventional drug delivery systems fail to provide, creating a “chronotherapy gap” that contributes to chronic wound pathologies. Hydrogels, with their highly tunable network structures, offer a unique platform to program release kinetics in synchrony with these healing timelines. This review systematically examines design strategies for phase-synchronized hydrogel systems, categorized into three hierarchical paradigms: intrinsic network control (crosslinking density, degradation kinetics, and architectural engineering) that pre-programs release profiles; extrinsic/responsive control (endogenous pH/ROS/MMP/glucose and exogenous NIR/ultrasound/electro/magnetic triggers) that enables on-demand phase-shifting; and integrated systems that combine passive spatial compartmentalization with active responsiveness. We survey representative applications across cutaneous wounds, bone defects, cartilage, tendon, myocardial, and neural tissues, highlighting both common design principles and tissue-specific adaptations. Key translational bottlenecks—including in vivo–in vitro discrepancies, cargo stability, sterilization challenges, and regulatory complexity—are critically examined, alongside emerging frontiers such as closed-loop biosensing, artificial intelligence-driven design, and four-dimensional printing. We conclude that the field is evolving from passive drug depots toward active therapeutic synchronizers, where material programming is set to the body’s biological clock, offering a transformative paradigm for regenerative medicine. Full article

Bioadhesive hydrogels combine tissue-adhesive properties with therapeutic multifunctionality, offering promising solutions for regenerative medicine. This comprehensive review examines the design strategies, fundamental adhesion mechanisms, and clinical applications of these biomaterials. We systematically discuss four primary adhesion mechanisms: physical interactions, chemical adhesion, topological mechanical interlocking, and bioinspired adhesion. Key design parameters, including wet-environment adhesion strength, self-healing capability, injectability, and controlled biodegradability, are analyzed and benchmarked against commercial products. Major material platforms, encompassing catechol-based systems, chitosan derivatives, gelatin/GelMA variants, Polyethylene glycol (PEG)-based adhesives, and multi-network hybrid systems, are evaluated for their adhesive performance and functional integration. Tissue-specific applications spanning wound healing, bone/cartilage repair, soft tissue sealing, vascular repair, and neural regeneration are critically assessed, emphasizing in vivo outcomes and clinical translation barriers. Finally, we discuss emerging frontiers, including artificial intelligence-guided material design, on-demand detachable adhesives, and regulatory pathways. Synthesizing over 140 peer-reviewed references from the past two decades, this review provides a systematic roadmap from fundamental adhesion science toward the clinical implementation of next-generation bioadhesive hydrogels. Full article