Search Results (577)

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

Healing large bone defects remains challenging. Gelatin scaffolds are biocompatible and biodegradable, but lack osteoinductive activity. Plant-derived exosomes carry miRNAs, growth factors, and proteins that modulate osteogenesis, but free exosomes suffer from poor stability, limited targeting, and low bioavailability in vivo. We developed a 3D GelMA hydrogel loaded with Epimedium-derived exosomes (“GelMA@Exo”) to improve exosome retention, stability, and sustained release. Its effects on MC3T3-E1 preosteoblasts—including proliferation, osteogenic differentiation, migration, and senescence—were evaluated via in vitro assays. Angiogenic potential was assessed using HUVECs. Underlying mechanisms were examined at transcriptomic and protein levels to elucidate GelMA@Exo’s therapeutic osteogenesis actions. GelMA@Exo exhibited sustained exosome release, enhancing exosome retention and cellular uptake. In vitro, GelMA@Exo markedly boosted MC3T3-E1 proliferation, migration, and mineralized nodule formation, while reducing senescence markers and promoting angiogenesis in HUVECs. Mechanistically, GelMA@Exo upregulated key osteogenic markers (RUNX2, TGF-β1, Osterix, COL1A1, ALPL) and activated the PI3K/Akt pathway. Transcriptomic data confirmed global upregulation of osteogenesis-related genes and bone-regeneration pathways. This study presents a GelMA hydrogel functionalized with plant-derived exosomes, which synergistically provides osteoinductive stimuli and structural support. The GelMA@Exo platform offers a versatile strategy for localized delivery of natural bioactive molecules and a promising approach for bone tissue engineering. Our findings provide strong experimental evidence for the translational potential of plant-derived exosomes in regenerative medicine. Full article

Urban sustainability challenges demand integrated frameworks capable of addressing the dynamic, non-linear nature of cities. This study explores how the principles of the circular economy and complexity theory intersect to support systemic transformation in sustainable urban planning. Through a systematic literature review of 71 peer-reviewed articles published between 2015 and 2025, we analyze conceptual, methodological, and practical articulations across multiple thematic axes, including circular governance, urban metabolism, regenerative design, adaptive planning, digital integration, and environmental justice. Bibliometric and content analyses were conducted using Scopus metadata, VOSviewer for thematic clustering, and the StArt software (Version 3.4) to structure article selection. The findings reveal that circular economy provides practical tools for resource efficiency and regeneration, while complexity theory offers an adaptive framework to navigate uncertainty, emergent behaviors, and feedback dynamics. The synthesis suggests that their integration enables a more holistic and resilient approach to urban transformation. However, gaps remain in social inclusivity, long-term assessment, and the operationalization of complexity-informed planning. This study contributes to advancing a transdisciplinary agenda for circular and adaptive urban futures, offering insights for scholars, planners, and policymakers aiming to reconfigure cities within planetary boundaries. Full article

Ozone (O₃) occurs in nature as a chemical compound made of three oxygen atoms. It is an unstable, highly oxidative gas that rapidly decomposes into oxygen. The therapeutic use of O₃ dates back to the beginning of the 20th century and is currently based on the application of low doses, inducing a moderate oxidative stress that stimulates the antioxidant cellular defenses without causing cell damage. Low O₃ doses also induce anti-inflammatory and regenerative effects, and their anticancer potential is under investigation. In addition, the oxidative properties of O₃ make it an excellent antibacterial, antimycotic, and antiviral agent. Thanks to these properties, O₃ is currently widely used in several medical fields. However, its chemical instability represents an application limit, and ozonated oil is the only stabilized form of medical O₃. In recent years, novel O₃ formulations have been proposed for their sustained and more efficient administration, based on nanotechnology. This review offers an overview of the nanocarriers designed for the delivery of medical O₃, and of their therapeutic applications. The reviewed articles demonstrate that research is active and productive, though it is a rather new entry in the nanotechnological field. Liposomes, nanobubbles, nanoconstructed hydrogels, polymeric nanoparticles, and niosomes were designed to deliver O₃ and have been proven to exert antiseptic, anticancer, and pro-regenerative effects when administered in vitro and in vivo. Improving the therapeutic administration of O₃ through nanocarriers is a just-started challenge, and multiple prospects may be foreseen. Full article

The escalating climate crisis and global disruptions have prompted a critical re-evaluation of operations management within manufacturing and supply systems. This conceptual article addresses the theoretical and strategic gap in aligning resilience and sustainability by proposing an Integrated Sustainable Operational Strategy (ISOS) framework. Drawing on systems theory, circular economy principles, and sustainability science, the framework synthesizes multiple operational domains—circularity, localization, digital adaptation, and workforce flexibility—across macro (policy), meso (organizational), and micro (process) levels. This study constructs a conceptual model that explains the interdependencies and trade-offs among strategic operational responses in the Anthropocene era. Supported by multi-level logic and a synthesis of domain constructs, the model provides a foundation for empirical investigation and strategic planning. Key propositions for future research are developed, focusing on causal relationships and boundary conditions. The novelty of ISOS lies in its simultaneous integration of three strategic pillars—circularity, localization, and digital resilience—within a unified, multi-scalar architecture that bridges fragmented operational theories. The article advances theory by redefining operational excellence through regenerative logic and adaptive capacity, responding directly to SDG 9 (industry innovation), SDG 12 (responsible consumption and production), and SDG 13 (climate action). This integrative framework offers both theoretical insight and practical guidance for transforming operations into catalysts of sustainable transition. Full article

Moringa oleifera (MO), a nutritionally and pharmacologically potent species, is emerging as a sustainable candidate for applications across bioenergy, agriculture, textiles, pharmaceuticals, and biomedicine. This review explores recent advances in MO-based biotechnologies, highlighting novel extraction methods, green nanotechnology, and clinical trial findings. Although MO’s resilience offers promise for climate-smart agriculture and public health, challenges remain in standardizing cultivation and verifying therapeutic claims. This work underscores MO’s translational potential and the need for integrative, interdisciplinary research. MO is used in advanced materials, like electrospun fibers and biopolymers, showing filtration, antibacterial, anti-inflammatory, and antioxidant properties—important for the biomedical industry and environmental remediation. In textiles, it serves as an eco-friendly alternative for wastewater treatment and yarn sizing. Biotechnological advancements, such as genome sequencing and in vitro culture, enhance traits and metabolite production. MO supports green biotechnology through sustainable agriculture, nanomaterials, and biocomposites. MO shows potential for disease management, immune support, metabolic health, and dental care, but requires further clinical trials for validation. Its resilience is suitable for land restoration and food security in arid areas. AI and deep learning enhance Moringa breeding, allowing for faster, cost-effective development of improved varieties. MO’s diverse applications establish it as a key element for sustainable development in arid regions. Full article

Neuronal proteins synthesized locally in axons and dendrites contribute to growth, plasticity, survival, and retrograde signaling underlying these cellular processes. Advances in molecular tools to profile localized mRNAs, along with single-molecule detection approaches for RNAs and proteins, have significantly expanded our understanding of the diverse proteins produced in subcellular compartments. These investigations have also uncovered key molecular mechanisms that regulate mRNA transport, storage, stability, and translation within neurons. The long distances that axons extend render their processes vulnerable, especially when injury necessitates regeneration to restore connectivity. Localized mRNA translation in axons helps initiate and sustain axon regeneration in the peripheral nervous system and promotes axon growth in the central nervous system. Recent and ongoing studies suggest that axonal RNA transport, storage, and stability mechanisms represent promising targets for enhancing regenerative capacity. Here, we summarize critical post-transcriptional regulatory mechanisms, emphasizing translation in the axonal compartment and highlighting potential strategies for the development of new regeneration-promoting therapeutics. Full article

As the global population continues to age, the incidence of neurodegenerative diseases and neural injuries is increasing, presenting major challenges for healthcare systems. Due to the brain’s limited regenerative capacity, there is an urgent need for strategies that promote neuronal repair and functional integration. Brain-derived neurotrophic factor (BDNF) is a key regulator of synaptic plasticity and neuronal development. In this study, we investigated whether constitutive BDNF expression in human induced pluripotent stem cell (iPSC)-derived neural progenitor cells (NPCs) enhances their neurogenic and integrative potential in vitro. We found that NPCs engineered to overexpress BDNF produced neuronal cultures with increased numbers of mature and spontaneously active neurons, without altering the overall structure or organization of functional networks. Furthermore, BDNF-expressing neurons exhibited significantly greater axonal outgrowth, including directed axon extension in a compartmentalized microfluidic system, suggesting a chemoattractive effect of localized BDNF secretion. These effects were comparable to those observed with the early supplementation of recombinant BDNF. Our results demonstrate that sustained BDNF expression enhances neuronal maturation and axonal projection without disrupting network integrity. These findings support the use of BDNF not only as a therapeutic agent to improve cell therapy outcomes but also as a tool to accelerate the development of functional neural networks in vitro. Full article

Sustainable farmland management is vital for global food security and for mitigating environmental degradation and climate change. While individual practices such as crop rotation and no-tillage are well-documented, this review synthesizes current evidence to illuminate the critical synergistic effects of integrating four key strategies: crop rotation, conservation tillage, organic amendments, and soil microbiome management. Crop rotation enhances nutrient cycling and disrupts pest cycles, while conservation tillage preserves soil structure, reduces erosion, and promotes carbon sequestration. Organic amendments replenish soil organic matter and stimulate biological activity, and a healthy soil microbiome boosts plant resilience to stress and enhances nutrient acquisition through key functional groups like arbuscular mycorrhizal fungi (AMFs). Critically, the integration of these practices yields amplified benefits that far exceed their individual contributions. Integrated management systems not only significantly increase crop yields (by up to 15–30%) and soil organic carbon but also deliver profound global ecosystem services, with a potential to sequester 2.17 billion tons of CO₂ and reduce soil erosion by 2.41 billion tons annually. Despite challenges such as initial yield variability, leveraging these synergies through precision agriculture represents the future direction for the field. This review concludes that a holistic, systems-level approach is essential for building regenerative and climate-resilient agroecosystems. Full article

In response to growing environmental pressures and material constraints, circular economy principles are gaining traction across manufacturing sectors. However, most existing frameworks emphasize design and supply chain considerations, with limited focus on how circularity can be operationalized within internal manufacturing systems. This paper proposes a conceptual model that embeds circular operations at the core of production strategy. Grounded in circular economy theory, operations management, and socio-technical systems thinking, the model identifies four key operational pillars: circular input management, looping process and waste valorization, product-life extension, and reverse logistics. These are supported by enabling factors—digital infrastructure, organizational culture, and leadership—and mediated by operational flexibility, which facilitates adaptive, closed-loop performance. The model aims to align internal processes with long-term sustainability outcomes, specifically resource efficiency and operational resilience. Practical implications are outlined for resource-intensive industries such as automotive, electronics, and FMCG, along with a readiness assessment framework for guiding implementation. This study offers a pathway for future empirical research and policy development by integrating circular logic into the structural and behavioral dimensions of operations. The model contributes to advancing the Sustainable Development Goals (SDGs), particularly SDG 9 and SDG 12, by positioning circularity as a regenerative operational strategy rather than a peripheral initiative. Full article

This paper presents a high-fidelity multi-physics dynamic model for electric vehicles, serving as a fundamental building block for intelligent vehicle-to-grid (V2G) integration systems. The model accurately captures complex vehicle dynamics of the powertrain, battery, and regenerative braking, enabling precise energy consumption evaluation, including in AI-driven V2G scenarios. Validated using real-world data from a Citroën Ami operating on urban routes in Naples, Italy, it achieved exceptional accuracy with a root mean square error (RMSE) of 1.28% for dynamic state of charge prediction. This robust framework provides an essential foundation for AI-driven digital twin technologies in V2G applications, significantly advancing sustainable transportation and smart grid integration through predictive simulation. Its versatility supports diverse fleet applications, from residential energy management and coordinated charging optimization to commercial car sharing operations, leveraging backup power during peak demand or grid outages, so to maximize distributed battery storage utilization. Full article

Marine biomass represents a valuable yet underexploited resource for the development of high-value biomaterials. Recent advances have highlighted the significant potential of marine-derived polysaccharides, proteins, and peptides in biomedical applications, most notably in drug delivery and wound healing. This review provides a comprehensive synthesis of current research on the extraction, processing and pharmaceutical valorization of these biopolymers, with a focus on their structural and functional properties that allow these materials to be engineered into nanocarriers, hydrogels, scaffolds, and smart composites. Key fabrication strategies such as ionic gelation, desolvation, and 3D bioprinting are critically examined for their role in drug encapsulation, release modulation, and scaffold design for regenerative therapies. The review also covers preclinical validation, scale-up challenges, and relevant regulatory frameworks, offering a practical roadmap from sustainable sourcing to clinical application. Special attention is given to emerging technologies, including stimuli-responsive biomaterials and biosensor-integrated wound dressings, as well as to the ethical and environmental implications of marine biopolymer sourcing. By integrating materials science, pharmaceutical technology and regulatory insight, this review aims to provide a multidisciplinary perspective for researchers and industrial stakeholders seeking sustainable and multifunctional pharmaceutical platforms for precision medicine and regenerative therapeutics. Full article

Background and Objective: Intervertebral disc degeneration (IVDD) is a leading cause of lower back pain with limited regenerative treatments. Among emerging regenerative approaches, growth factor-based therapies, such as recombinant human transforming growth factor-beta (Rh-TGF-β), have shown potential for disc regeneration but are hindered by rapid degradation and uncontrolled release by direct administration. Additionally, mechanical stress elevates heat shock protein 90 (HSP-90), impairing cell function and extracellular matrix (ECM) production. This study aimed to investigate a dual self-cross-linked alginate di-aldehyde (ADA) hydrogel system for the sustained delivery of Rh-TGF-β and epigallocatechin gallate (EGCG) to enhance protein stability, regulate release, and promote disc regeneration by targeting both regenerative and stress-response pathways. Methods: ELISA and UV-Vis spectrophotometry assessed Rh-TGF-β and EGCG release profiles. A rat tail IVDD model was established with an Ilizarov-type external fixator for loading, followed by hydrogel treatment with or without bioactive agents. Disc height, tissue structure, and protein expression were evaluated via radiography, histological staining, immunohistochemistry, and Western blotting. Results: The hydrogel demonstrated a biphasic release profile with 100% Rh-TGF-β released over 60 days and complete EGCG release achieved within 15 days. Treated groups showed improved disc height, structural integrity, and proteoglycan retention revealed by histological analysis and elevated HSP-90 expression by immunohistochemistry. In contrast, Western blot analysis confirmed that EGCG effectively downregulated HSP-90 expression, suggesting a reduction in mechanical stress-induced degeneration. Conclusions: ADA hydrogel effectively delivers therapeutic agents, offering a promising strategy for IVDD treatment. Full article

This study examines the role of public–private partnerships in promoting the sustainable development of travel destinations through a comparative analysis of two emblematic heritage-based hospitality projects: Dar Tantora in Al Ula, Saudi Arabia, and Sextantio Le Grotte della Civita in Matera, Italy. These case studies were analysed through both architectural–urban and economic–legal perspectives to highlight how public–private partnership models can support heritage conservation, community engagement, and responsible tourism development. A mixed-methods approach was employed, combining quantitative indicators—such as projected profitability, tourist volume, and employment—with qualitative insights from interviews with key stakeholders. The analysis reveals that while both models prioritise cultural authenticity and adaptive reuse, they differ significantly in funding structures, legal frameworks, and governance dynamics. Dar Tantora exemplifies a top-down, publicly funded model integrated into Saudi Arabia’s Vision 2030 strategy, whereas Sextantio reflects a bottom-up, private initiative rooted in social enterprise. The findings offer insights into how different public–private partnership configurations can foster sustainable tourism development, depending on local context, institutional frameworks, and strategic goals. The study contributes to the broader discourse on regenerative tourism, architectural conservation, and policy-driven heritage reuse. Full article

Plant-derived vesicle-like nanoparticles (PDVLNs) are bioactive nanovesicles secreted by plant cells, emerging as a novel therapeutic tool for tissue repair and regeneration due to their low immunogenicity, intrinsic bioactivity, and potential as drug delivery carriers. This review examines PDVLNs’ biogenesis mechanisms, isolation techniques, and compositional diversity, emphasizing their roles in promoting essential regenerative processes—cell proliferation, differentiation, migration, immune modulation, and angiogenesis. We explore their therapeutic applications across multiple tissue types, including skin, bone, neural, liver, gastrointestinal, cardiovascular, and dental tissues, using both natural and engineered PDVLNs in various disease models. Compared to mammalian exosomes, PDVLNs offer advantages such as reduced immune rejection and ethical concerns, enhancing their sustainability and appeal for regenerative medicine. However, challenges in clinical translation, including scalability, standardization, and safety remain. This paper consolidates current knowledge on PDVLNs, highlighting their versatility and providing insights into engineering strategies to optimize efficacy, ultimately outlining future research directions to advance their clinical potential. Plant vesicle-like nanoparticles (PDVLNs) may become a new avenue for the treatment of tissue injury, promoting tissue repair and regeneration through their intrinsic bioactivity or as drug delivery carriers. In addition, PDVLNs can be engineered and modified to achieve better results. Full article