Search Results (2,336)

Plant-derived extracellular vesicles (PDEVs) have emerged as promising natural nanocarriers for biomedical applications owing to their distinctive ability to facilitate intercellular communication and transport bioactive molecules. In this review, we employ bibliometric analysis to identify research hotspots and trends, providing a comprehensive overview of these core themes. The bibliometric results reveal a sustained increase in annual publications in this field, with keyword analysis identifying drug delivery, cross-kingdom regulation, immunomodulation, engineering modification, and gut microbiota as five major research themes. The focus of research has evolved from early basic biological characteristics into engineered smart delivery platforms, with the application areas expanding from intestinal inflammation to neurological, metabolic, dermatological, and oncological diseases. This review systematically examines the core directions in this field. It compares the strengths and limitations of mainstream isolation methods and highlights the value of multi-omics integration, covering the molecular mechanisms of ferroptosis and gut microbiota regulation by PDEVs along with engineering strategies such as drug loading, surface modification, and membrane fusion. It also discusses the latest progress in frontier therapeutic applications of PDEVs, including cancer, inflammatory diseases, tissue regeneration and aesthetics, and neurological disorders. Finally, this review summarizes the key challenges confronting the field, including the lack of standardized protocols, production bottlenecks, and engineering obstacles. It also delineates future directions, including establishing international standardization definitions, advancing multi-omics and AI-driven mechanistic elucidation, developing scalable and efficient purification technologies, and executing systematic preclinical safety and pharmacokinetic evaluations to facilitate clinical translation. Full article

The tooth is a complex biological organ composed of multiple tissues, including enamel, dentine, cementum and pulp. However, dental disease and tooth loss due to periodontitis, caries, or trauma adversely affect most adults at some time in their lives. Tooth regeneration represents a shift in the dental paradigm from removal to repair to regeneration. Tooth regeneration is an extension of the broader field of regenerative medicine, aiming to restore a tissue defect to its original form and function by using biological substitutes to replace lost teeth or tooth tissue, providing a viable alternative to currently available clinical treatments. A full array of cell sources has been trialled for endodontic regeneration, following the basic premise of tissue engineering, including cells–scaffold–bioactive molecules. Several reports have documented dental pulp-like tissue regeneration, either in vitro or following the transplantation of stem cells. Tooth regeneration follows two unique approaches: cell transplantation and cell homing. Cell transplantation has been the predominant approach, whereas cell homing aims to achieve tissue repair and regeneration of the injury site through the chemotaxis of host endogenous cells. This narrative review explores therapeutically viable tooth regeneration approaches by contrasting cell transplantation and cell-to-scaffold methodologies focussing on the cell–scaffold–bioactive molecule triad. Full article

Chronic wounds constitute a major clinical and socioeconomic burden owing to prolonged inflammation, persistent bacterial infection, impaired angiogenesis, and defective extracellular matrix remodeling. Advanced wound dressings have traditionally been developed to promote tissue regeneration, control bacterial infection, and restore the wound microenvironment. Recent advances have focused on multifunctional biomaterials integrating regenerative, antibacterial, anti-inflammatory, antioxidant, and controlled drug-delivery properties. Within this context, antiviral biointerface engineering has emerged as a promising, although still exploratory, materials-engineering perspective rather than an established function of wound dressings. Hydrogel–metal–organic framework (MOF) hybrid polymer composites have emerged as versatile platforms for multifunctional wound dressings. Hydrogels provide hydrated three-dimensional matrices with tunable porosity, swelling behavior, mechanical compliance, and biocompatibility, whereas MOFs contribute high surface area, adjustable pore architectures, chemically tailorable active sites, and controlled ion release. Their integration generates synergistic systems whose performance is governed by structure–function relationships involving polymer crosslinking density, MOF dispersion, pore hierarchy, interfacial adhesion, swelling dynamics, and surface functionalization. Collectively, these parameters regulate mass transport, mechanical stability, therapeutic delivery, and cytocompatibility while potentially influencing virus–material interactions through engineered biointerfaces. Current evidence indicates that direct experimental demonstrations of antiviral performance in hydrogel–MOF wound dressing systems remain limited. Accordingly, antiviral biointerface functions should be regarded as emerging engineering opportunities requiring further experimental validation before clinical translation. This review critically analyzes the structure–function engineering principles governing hydrogel–MOF hybrid systems and examines how established regenerative functions may be integrated with emerging antiviral biointerface concepts. Unlike previous reviews focused primarily on drug delivery, antibacterial activity, or tissue engineering, this review emphasizes the relationships between polymer architecture, MOF chemistry, interfacial design, and transport phenomena while explicitly distinguishing experimentally supported evidence from prospective mechanistic concepts. Particular attention is given to current limitations, translational challenges, and future directions for the rational design of next-generation multifunctional hydrogel–MOF wound dressings. Full article

Fascia serves as both a mechanical scaffold and a progenitor cell reservoir critical for wound healing and tissue regeneration. This study developed an In Situ Induced Fascial Analogue (iFA) via low-growth-factor Matrigel injection into mouse subcutaneous fascia, using silicone as a control. At 14 days, histological and ultrastructural analyses showed that the iFA possessed an organized collagen architecture comparable to native fascia, distinct from the dense fibrous capsules in controls. qPCR and immunofluorescence revealed a pro-reparative macrophage-associated microenvironment characterized by increased CD206 expression and demonstrated the enrichment of CD34⁺/PDGFRα⁺ co-expressing telocytes (TCs) within the iFA, consistent with their characteristic molecular and ultrastructural features. Ex vivo assays demonstrated cell migratory activity, and in vivo wound healing assays showed that iFA-derived cells significantly accelerated wound closure and re-epithelialization. This study established a structurally biomimetic fascial analogue enriched with CD34⁺/PDGFRα⁺ TCs that avoids pathological fibrosis, providing a novel in situ engineering strategy for generating fascia-like tissues and a platform for future regenerative research. Full article

Myocardial infarction remains a leading cause of heart failure owing to the limited regenerative capacity of adult cardiac tissue, underscoring the need for biomimetic therapeutic platforms that combine structural support with biological functionality. Accordingly, this study aimed to develop a multifunctional electrospun cardiac patch by integrating decellularized neonatal porcine myocardial extracellular matrix (dECM), gelatin, and microbiota-derived postbiotics for cardiac tissue engineering. The fabricated patches were comprehensively characterized in terms of their morphology, mechanical properties, biodegradation behavior, antibacterial activity, antioxidant capacity, and in vitro biocompatibility. Postbiotics derived from Lactiplantibacillus plantarum EIR/IF-1 exhibited potent antimicrobial activity against methicillin-resistant Staphylococcus aureus, strong antioxidant capacity, and significant anti-inflammatory activity through the suppression of pro-inflammatory mediators and upregulation of IL-10 expression. Moreover, they protected H9c2 cardiomyoblasts from oxidative stress, promoted COL1A1 expression, and supported ECM remodeling. The fabricated electrospun cardiac patches exhibited a homogeneous nanofibrous architecture, mechanically suitable properties (Young’s modulus ~4 MPa), controlled biodegradation over 7 days, favorable cell viability, and maintained the biological functionality of the incorporated postbiotics. Overall, the synergistic integration of tissue-specific dECM and microbiota-derived postbiotics yielded a multifunctional biohybrid cardiac patch with favorable structural and biological properties, supporting its potential as a promising platform for myocardial regeneration and next-generation cardiac tissue engineering. Full article

Periodontal diseases are highly prevalent conditions characterized by chronic inflammation, which leads to progressive destruction of tooth-supporting tissues. Conventional therapies, including scaling and root planing, grafting, and surgical procedures, are effective in controlling infection but show limited regenerative capacity. In this context, hydrogels—three-dimensional, highly hydrated polymeric biomaterials that mimic the extracellular matrix—have emerged as promising tools in periodontal regeneration. These materials can be engineered to modulate mechanical properties, porosity, and the delivery of bioactive molecules. Hydrogels can function as barrier membranes for guided tissue regeneration, scaffolds for stem cell support, and carriers for antimicrobial, anti-inflammatory, and osteogenic agents, enabling sustained and localized drug release. Recent studies have demonstrated their potential to inhibit bacterial biofilms, enhance osteogenic differentiation, and reduce inflammation in preclinical models. However, challenges remain regarding mechanical stability in the oral environment, controlled and sequential release of therapeutic agents, biocompatibility, and cost-effectiveness. Overall, hydrogels represent a promising adjunct in regenerative periodontal therapy, although further research is required to support their translation into routine clinical practice. Full article

Restoration of the osteochondral unit remains a major challenge in regenerative orthopaedics, largely due to the limited intrinsic healing capacity of articular cartilage and the complex, multilayered nature of the cartilage–bone interface. Osteochondral regeneration must accommodate differences in cellular composition, vascularization, metabolic demand, and mechanical properties between cartilage and bone, while simultaneously recreating a stable, functional interface. While exogenous mesenchymal stem cell (MSC) therapies have dominated the field, their clinical translation has been hindered by donor variability, phenotypic instability, logistical complexity, and inconsistent long-term outcomes. Resident stem cells from sources such as articular cartilage, bone marrow, periosteum, synovium, synovial fluid, and adipose tissue (infrapatellar fat pad) can act as potential targets for in situ osteochondral regenerative therapies. Joint-resident MSCs are adapted to the biomechanical and biochemical environment of the joint and may therefore represent a promising cell source for osteochondral regeneration; however, much of the supporting evidence remains preclinical. Effective osteochondral repair depends on the precise orchestration of stem cell recruitment, maintenance of chondrogenic phenotypes, induction of osteogenic differentiation in the subchondral compartment, and modulation of local immune responses. Patient-specific factors, including age, inflammatory status, and the severity of osteoarthritis, can significantly influence the regenerative potential of resident MSC populations and should therefore guide biomaterial design strategies. The proposed niche-by-design framework integrates stem cell biology with advanced biomaterial engineering, offering a rational roadmap for developing next-generation therapies that promote endogenous osteochondral regeneration through targeted activation of joint-resident progenitor cells. Full article

Wound dressings play a crucial role in promoting tissue regeneration while protecting damaged tissue from microbial infections. The aim of this study is to produce antimicrobial PVA-chitosan membranes for wound dressing applications using Stevia rebaudiana Bertoni leaf extract (stevia) as a natural bioactive agent. Although widely recognized as a natural sweetener, stevia contains a high concentration of diterpene glycosides, particularly stevioside and rebaudioside A, together with phenolic compounds that contribute to its biological activities. Therefore, stevia was first evaluated against selected microorganisms and demonstrated effective antimicrobial activity. PVA-chitosan (P/Ch) membranes were prepared by solvent casting method by incorporating different amounts of stevia (P/Ch, P/Ch@20, P/Ch@40, and P/Ch@60). The antimicrobial activity of stevia was also successfully maintained in P/Ch membranes. Good antibacterial activity was observed against Bacillus subtilis and Escherichia coli, whereas the antifungal activity against Candida albicans was comparatively modest. Contact surface analysis showed complete bactericidal activity in Gram-negative and spore-forming bacteria. The cytocompatibility of the membranes was investigated by MTT assay. All formulations maintained a high cell viability (>80%) while the P/Ch@40 membrane increased the metabolic activity to above 100% at higher extract concentrations. In conclusion, stevia-incorporated membranes exhibited high antimicrobial activity, acceptable characteristic properties, and good cytocompatibility, suggesting that they are promising alternative biomaterials for tissue engineering applications. Full article

Massive segmental bone defects present significant challenges in orthopaedic and maxillofacial reconstruction. As defect size increases, the disparity between tissue volume and diffusion-limited biological processes becomes more pronounced. This narrative review analyses distinctions between centimetre-scale defects and conventional fractures and evaluates current tissue-engineering strategies in relation to vascularisation, osteogenesis, mechanical stability, immune response, neural integration, and manufacturability. This review synthesises evidence from scaffold design, cell-based approaches, growth factor delivery, type-H vessel biology, NGF–TrkA signalling, large-animal models, and early clinical translation. Current findings indicate that no single scaffold, cell source, or growth factor can reliably reproduce the coordinated biological and mechanical environment required for durable regeneration of human long bones. The strongest preclinical evidence is derived from ovine tibial models employing medical-grade polycaprolactone/β-tricalcium phosphate composites or mechanobiologically optimised titanium lattices. Human data remain limited to case reports and small early clinical series, including hybrid vascularised flap–scaffold reconstructions. Successful clinical translation will require patient-specific constructs that integrate rapid vascularisation, appropriate load sharing, immune-compatible degradation, infection control, and scalable manufacturing. Until robust comparative clinical evidence emerges, established reconstructive methods will remain the standard of care. Hybrid vascularised scaffold-guided strategies should be regarded as promising translational approaches rather than definitive solutions. Full article

Osteochondral defects, involving both articular cartilage and subchondral bone, can lead to joint degeneration and osteoarthritis. Recent advances in 3D-printed biphasic scaffolds offer promising opportunities to recreate physiological microenvironments for tissue regeneration. In tissue engineering, these scaffolds can be mechanically stimulated to promote targeted cartilage and bone formation. While computational models have been widely used to study mechanically induced cellular responses in monophasic scaffolds, time-dependent modelling of biphasic osteochondral systems remains relatively scarce. In this study, a fluid–structure interaction (FSI) framework coupled with a mechanoregulatory algorithm was developed to predict mechanically induced early-stage mesenchymal stem cell (MSC) differentiation in biphasic open-porous osteochondral scaffolds comprising chondral and bone layers designed for direct ink writing (DIW). In a second model, an interfacial barrier layer representing the native osteochondral interface was integrated. Dynamic compressive loading (1 Hz, $2.5\%$ strain) was applied. The simulations predicted region-specific differentiation patterns in both the chondral and subchondral bone regions. In the scaffold without a barrier layer, approximately $68.9\%$ of MSCs in the chondral layer and $93.4\%$ of MSCs in the bone layer underwent chondrogenic and osteogenic differentiation, respectively. Incorporation of the barrier layer caused only minor changes, reducing predicted cartilage and bone differentiation by approximately $1.5\%$ and $3.9\%$, respectively. Overall, this study highlights the capability of computational modelling to predict mechanobiological responses in complex osteochondral systems and support scaffold design and effective mechanical stimulation protocols. Full article

Plant tissue culture is a crucial part of biotechnology that supports crop improvement, plant conservation, and other related fields. Although tissue culture has been successfully used in many plants, low regeneration and transformation rates still exist in some species. Agrobacterium-mediated transformation is commonly used in genetic engineering, but its effectiveness depends heavily on establishing a reliable in vitro regeneration system through organogenesis or somatic embryogenesis. Over the past decade, substantial progress has been made in understanding the molecular basis of regeneration; however, most reviews have focused on individual aspects such as hormone regulation or transcription factor networks in isolation. In contrast, this review provides a comprehensive and integrated framework that systematically links four critical layers—wound signaling, hormonal regulation, developmental regulators, and epigenetic modifications—into a unified regulatory network governing plant regeneration. Furthermore, we highlight recent cutting-edge advances, including artificial intelligence-assisted prediction, single-cell and spatial transcriptomics, epigenome editing, and CRISPR-based activation systems, and we discuss their transformative potential in overcoming genotype-dependent recalcitrance. By synthesizing classical regulatory mechanisms with emerging technologies, this review offers a forward-looking perspective that distinguishes it from earlier publications and provides both theoretical foundations and practical strategies for improving plant regeneration and genetic transformation. Full article

Vascularization remains a fundamental bottleneck in tissue engineering, as the absence of functional vascular networks limits oxygen and nutrient delivery, resulting in necrotic cores and poor host integration. While structural scaffold design and cell sourcing have advanced considerably, emerging evidence indicates that paracrine signaling, rather than direct cell contact or scaffold architecture alone, is the primary driver of angiogenesis and vasculogenesis within engineered constructs. Key cell types, including endothelial cells (ECs) and mesenchymal stem cells (MSCs), engage in bidirectional paracrine crosstalk through the secretion of vascular endothelial growth factor (VEGF), angiopoietins, hepatocyte growth factor, and platelet-derived growth factor, among other mediators. While researchers have long focused on improving scaffold structure and cell selection, growing evidence shows that the chemical messages cells send to one another play a far more important role in driving blood vessel formation than previously appreciated. This review explores how cells embedded within engineered scaffolds communicate through secreted signals to coordinate the growth of new blood vessels. Two cell types, MSCs and ECs, are central to this process: cells that line blood vessels and bone marrow-derived stem cells. These cells exchange a variety of chemical messages that instruct neighboring cells to multiply, move, and organize into vessel-like structures. Importantly, the material properties of the scaffold itself, including its stiffness, surface texture, and degradation over time, influence the signals cells produce and how those signals spread through the tissue. Strategies to amplify paracrine signaling include growth factor-loaded delivery systems, hypoxic and genetic preconditioning of MSCs, and perfusion bioreactor culture. In vitro and in vivo evidence consistently demonstrates that coculture systems leveraging paracrine interactions produce superior vascular outcomes compared to single-cell or acellular constructs. Despite this progress, challenges related to signaling complexity, reproducibility, and clinical translation persist. Integration of transcriptomic and proteomic profiling, computational modeling, and machine learning approaches offers a path toward rationally designed scaffolds that recapitulate the spatiotemporal dynamics of native vascular signaling and ultimately support functional tissue regeneration. Full article

Neurological disorders, including stroke, traumatic brain injury, and spinal cord injury, constitute one of the most important causes of mortality and morbidity worldwide for which current treatment options focus on resolving neuroinflammation rather than on tissue and neuronal regeneration. Mesenchymal stem cells (MSCs) could be a potential therapeutic option due to their immunomodulatory, neuroprotective, and paracrine secretion of extracellular vesicles and trophic factors which modulate microglial activation, preserve blood–brain barrier (BBB) integrity, and neuroplasticity, but with limitations due by poor survival, retention, and phenotypic instability following direct transplantation. The purpose of this narrative review is to present mechanotransduction signaling pathways (integrin–FAK, PI3K/Akt, Rho/ROCK, and YAP/TAZ) through which MSC-based biomaterial scaffolds, especialy hyaluronic acid (HA) hydrogels, make the transition from reparative to regenerative medicine in central nervous system (CNS) injury. Even if most of the evidence from preclinical studies suggests that dynamically tunable MSC-scaffold systems represent promising platforms for neural tissue engineering and regenerative medicine, further translational studies and well-designed clinical investigations are required to establish their therapeutic efficacy and clinical applicability. Full article

The meniscus is a fibrocartilaginous tissue essential for load transmission, shock absorption, joint stability, and cartilage protection in the knee. However, its intrinsic healing capacity is severely limited, particularly in the avascular region and in complex defects, often resulting in persistent symptoms, functional impairment, and progressive joint degeneration. Although current clinical interventions, including meniscal repair, partial meniscectomy, allograft transplantation, and scaffold-assisted meniscal substitution, can provide symptomatic and functional improvement in selected patients, durable structural and functional restoration remains difficult to achieve. Meniscus tissue engineering has therefore emerged as a potential strategy for tissue preservation and functional reconstruction. This review synthesizes recent advances in meniscus tissue-engineered scaffolds, focusing on biomaterial systems, biofabrication strategies, and translational progress. Natural polymers, decellularized extracellular matrix, synthetic polymers, and composite materials are discussed according to their respective roles in biological regulation, mechanical support, structural organization, and clinical feasibility. Emerging biofabrication strategies are further analyzed with respect to geometric reconstruction, zonal organization, fibrous anisotropy, and their implications for scaffold evaluation. Finally, current in vitro, preclinical, and clinical evidence is critically examined to identify the key barriers that still limit long-term regeneration and clinical translation. Full article

Thermoplastic polyurethane (TPU) is an important polymer widely used in biomedical applications owing to its flexibility, strength, low toxicity, and biocompatibility. The TPU structure is classified into two types—soft and hard segments—which can be easily modified to achieve the desired mechanical and biological properties, making TPU an ideal material for wound healing and smart healthcare systems. Unlike conventional thermoset polyurethanes, TPU has a segmented architecture with soft and hard domains that undergo microphase separation. This unique structure provides an excellent balance of elasticity, toughness, flexibility, and processability, allowing TPU to better mimic the mechanical behavior of soft biological tissues, making it suitable for wound healing and smart healthcare applications. TPU-based dressings provide a moist environment, allow oxygen to pass through, and protect wounds from bacterial infection. Compared with traditional materials, TPU offers greater elasticity, durability, and patient comfort. In addition, TPU plays a key role in wearable sensors, electronics, and real-time monitoring devices. TPU-based smart materials can detect pH, temperature, and moisture levels to monitor wound conditions and overall patient health. This review highlights the potential of TPU as a promising material for wound healing and numerous smart healthcare applications. Full article