Search Results (204)

Sepsis is a life-threatening syndrome characterized by severe immune dysregulation, frequently culminating in acute respiratory distress syndrome (ARDS) and acute kidney injury (AKI). Current supportive therapies fail to reverse the underlying pathophysiological damage. However, mesenchymal stromal cells (MSCs) have emerged as a promising therapeutic frontier due to their robust immunomodulatory, anti-inflammatory, and tissue-regenerative properties. Despite compelling preclinical evidence, translating these benefits into consistent clinical efficacy remains a major challenge. This review critically examines the biological and anatomical barriers limiting the efficacy of MSCs, particularly the pulmonary first-pass effect, which restricts the systemic delivery of viable cells to distant organs such as the kidneys. To overcome these physical limitations, we highlight the recent paradigm shift toward nanoscale, cell-free therapies, specifically MSC-derived extracellular vesicles (MSC-EVs). EVs effectively bypass pulmonary sequestration and thromboembolic risks, exerting their potent therapeutic effects through the horizontal transfer of bioactive cargo, notably microRNAs, to reprogram cellular fate and restore immune homeostasis. We also discuss the critical need for rigorous clinical trial designs, scalable good manufacturing practice protocols, and the integration of a precision medicine approach. Ultimately, incorporating validated biomarkers for targeted patient stratification will be the decisive step in unlocking the full therapeutic potential of MSCs and their derivatives in critical care. Full article

Three-dimensional (3D) bioprinting has emerged as a versatile biofabrication strategy that enables the precise, spatiotemporally controlled co-deposition of living cells, biomaterials, and bioactive agents, including growth factors, cytokines, and extracellular matrix (ECM) components, into geometrically defined 3D constructs. By translating digital design models derived from computed tomography (CT), magnetic resonance imaging (MRI), or computational modeling directly into physical tissue architectures, 3D bioprinting facilitates the assembly of hierarchically organized constructs that closely recapitulate the structural, mechanical, and functional characteristics of native tissues. The principal 3D bioprinting strategies are broadly classified into scaffold-based and scaffold-free approaches. Engineered bioinks, whether formulated as cell-laden natural, synthetic, or composite polymer hydrogels, tissue-derived decellularized ECM (dECM) components, or pure cellular spheroids and organoids, constitute the cornerstone of these biofabrication platforms. Scaffold-based 3D bioprinting comprises extrusion-based, droplet-based (inkjet and drop-on-demand), light-based vat photopolymerization (stereolithography and digital light processing), and laser-assisted bioprinting based on laser-induced forward transfer (LIFT). Each of these modalities imposes distinct constraints on bioink rheology, crosslinking mechanisms, spatial resolution, throughput, and post-printing cell viability; consequently, a specific 3D bioprinting strategy is selected according to the specific requirements of the target tissue application. Scaffold-free 3D bioprinting and bioassembly techniques, including the Kenzan method, aspiration-assisted bioprinting, magnetic bioprinting, and other field-directed tissue assembly approaches, enable the fabrication of spheroid- and organoid-based constructs without the necessity for exogenous biomaterial scaffolds. Because native tissues exhibit diversity in cellular composition, ECM architecture, mechanical properties, and physiological function, no individual bioprinting platform or bioink formulation serves as a universal 3D bioprinting solution. The engineering of biomimetic tissue constructs, therefore, requires the selection of application-tailored fabrication approaches. Under this biofabrication paradigm, 3D bioprinting has been applied across a wide range of tissue engineering targets, including skin, bone, cartilage, osteochondral interfaces, cardiac and vascular tissue, neural structures, ocular, dental, and adipose tissue. This review discusses recent advances in scaffold-based and scaffold-free 3D bioprinting applications for tissue engineering and regenerative medicine across diverse tissue systems. Full article

The effect of light spectrum conversion using photoconversion covers (PCCs) containing CdSe/CdS-ZnS quantum dots (PCC-QDs) on the growth and photosynthesis of tomato plants was studied. Luminophore-free covers and covers containing rhodamine B as a luminophore (PCC-RB) were used as reference covers. The obtained covers had a luminescence maximum in the red region (618 nm for PCC-QDs and 615 nm for PCC-RBs). It was shown that both types of PCC promoted plant growth, with PCC-QDs increasing leaf number by 28% and chlorophyll content by 6%, while PCC-RB enhanced stem length (17%) and leaf number (23%), with no effect on chlorophyll content after a reduction in the thermal dissipation of absorbed light energy and intensifying electron transfer in the photosynthetic electron transport chain, which was accompanied by a 40–50% increase in the hydrogen peroxide content in plant tissues and a 2–3-fold increase in ascorbate peroxidase activity. Light-induced activation of transpiration in PCC plants was found to occur within 1–2 min, while control plants exhibited greater stomatal inertia with a 4–5 min delay in response to light. It is assumed that changes in the light spectrum induced by PCCs led to the optimization of electron transport in chloroplasts, triggering H₂O₂-mediated activation of gas exchange in leaves. Full article

Volumetric muscle loss (VML) constitutes a significant clinical challenge, defined by the irreversible loss of skeletal muscle tissue and resulting in persistent functional deficits due to fibrosis, chronic inflammation, and insufficient endogenous regeneration. Existing clinical interventions, such as autologous grafting and free functional muscle transfer, are constrained by donor-site morbidity including infection, pain, suboptimal vascularization, and limited functional integration. Although tissue engineering has advanced considerably, no FDA-approved regenerative therapies currently exist for VML, underscoring a substantial translational gap. This review provides a systems-level synthesis of skeletal muscle repair through integrating fundamental biological processes, such as inflammation, satellite-cell activation, myogenesis, angiogenesis, and neuromuscular junction formation, with recent advances in biomaterials, scaffold engineering, and biofabrication technologies. The analysis addresses how critical scaffold design parameters, including alignment, porosity, stiffness, degradation kinetics, and bioactivity, influence cellular responses and tissue integration. Additionally, emerging strategies such as 3D bioprinting, nanofiber-based architectures, stem cell and exosome therapies, and bio-functional stimulation are evaluated inside a unified mechanobiological framework. This analysis is further extended to the regulatory setting, with emphasis on how scaffold composition, mechanism of action, and degree of biological integration affect classification pathways governed by the U.S. Food and Drug Administration. Most advanced VML therapies are anticipated to be regulated as combination products, which will require rigorous preclinical validation, standardized manufacturing processes, and carefully designed clinical studies. By integrating biological principles, engineering design, and regulatory considerations, this review highlights key opportunities, remaining challenges, and future priorities for the clinical translation of next-generation regenerative strategies for VML. Full article

Vital pulp therapy aims to preserve pulp vitality by stimulating reparative processes. However, conventional approaches often result in incomplete tissue regeneration. Extracellular vesicles (EVs) have emerged as promising cell-free therapeutic agents because of their ability to regulate angiogenesis, odontogenesis, and immune responses through the transfer of bioactive molecules. Despite their significant regenerative potential, the clinical application of EVs remains limited by rapid clearance, insufficient local retention, and uncontrolled release following administration. To address these challenges, various extracellular matrix (ECM)-based and ECM-bioinspired scaffolds have been developed as delivery platforms. These scaffolds can provide structural support and enable controlled, localized release of EVs. This narrative review critically evaluates the current evidence regarding scaffold systems as EV delivery platforms for dental pulp regeneration, comparing their biological performance, methodological quality, and translational potential. Across the available studies, scaffold-assisted EV delivery consistently enhanced angiogenesis, odontogenic differentiation, mineralization, and immunomodulation; however, the evidence remains preclinical and is characterized by substantial heterogeneity regarding EV source, isolation and characterization methods, scaffold composition, experimental models, and outcome assessment. Current findings support the feasibility of scaffold-assisted EV delivery for regenerative endodontics, but important challenges remain, including standardization of EV production and characterization, scalable manufacturing, regulatory approval, and demonstration of long-term safety and functional pulp–dentin complex regeneration. Further well-designed translational and clinical studies will be essential before routine clinical implementation can be considered. Full article

Scaffolds designed for mechanically demanding soft tissue engineering applications should integrate mechanical support, efficient mass transfer, and good cellular compatibility. This work presents a one-pot method based on “radical-free click chemistry + carbodiimide coupling” to produce a double-network (DN) PEG–alginate cryogel. The PEG network is formed by a Michael addition reaction between thiol-based crosslinker and 8-arm PEG-acrylate. The second network is covalently crosslinked through EDC/NHS-mediated coupling of carboxyl groups in alginate and adipic acid dihydrazide (AAD). The subsequent freezing and gelation of the gel precursor at sub-zero temperatures results in an ice templated cryogel with an interconnected macroporous network. These cryogels demonstrate high elasticity, compressive modulus and rapid swelling equilibrium in aqueous environments, as well as controlled degradation under physiological conditions. Compared to the classical Ca²⁺ ion crosslinking systems, the covalent linking of the alginate in the double-network cryogel shows advantages in mechanical and structural stability. In addition, it is cell-compatible and allows culture of mesenchymal stem cells (MSCs) with homogeneous infiltration. Furthermore, the double-network cryogels supports chondrogenic differentiation of MSCs upon treatment with chondrogenic media or macrophage-conditioned media for a short period of time. These results indicate that crosslinking chemistry and polymer composition can be used to modulate the balance between mechanical performance and degradation behavior, while maintaining cytocompatibility and an interconnected macroporous network, thereby providing a scaffold design strategy for applications that require coordinated mechanical support and mass transfer, such as cartilage-related tissue engineering. Full article

Quadriceps muscle and tendon injuries are a significant cause of impairment of the knee extensor mechanism, ranging from minor muscle strains to complete tendon ruptures and extensive defects following oncologic resections. This narrative review provides a comprehensive analysis of contemporary concepts in anatomy, biomechanics, diagnosis, surgical management, and rehabilitation, with a particular focus on reconstructive techniques and functional outcomes. While most muscle injuries respond well to conservative management, complete quadriceps tendon ruptures typically require surgical repair to restore extensor continuity. Both transosseous suture techniques and suture anchor fixation demonstrate reliable outcomes, with no clear superiority in clinical results. Chronic ruptures present additional challenges due to tendon retraction and poor tissue quality, often necessitating advanced reconstruction methods such as V–Y tendon lengthening and augmentation with autografts, allografts, or synthetic materials. In cases of large defects, especially following soft-tissue sarcoma resection, free functional muscle transfer (FFMT) has emerged as a key reconstructive strategy. Common donor muscles include the latissimus dorsi, gracilis, rectus abdominis, and vastus lateralis, each offering specific biomechanical advantages. Functional recovery is strongly influenced by the extent of quadriceps preservation, with better outcomes observed when at least two muscle heads remain functional. Rehabilitation protocols vary depending on the surgical approach. Early controlled mobilisation is generally recommended after tendon repair, whereas FFMT requires a more cautious and prolonged rehabilitation process to allow for flap integration and reinnervation. Overall, optimal outcomes depend on a multidisciplinary approach combining appropriate surgical technique, individualized rehabilitation, and careful patient selection. Full article

Background: Maize is a vital crop, supporting 19.5% of global calorie intake. However, maize is vulnerable to even brief periods of drought which substantially reduces seed set and therefore yield. Methods: To identify proteins involved in responses of maize to drought, soluble proteins were extracted from leaf and silk tissues of Zea mays and protein abundance and phosphorylation status were quantified relative to well-watered controls. Label-free quantification and phosphopeptide enrichment were applied to the same biological samples and over 300 proteins were identified with significantly different changes. Results: Proteins known to be involved in drought responses were identified, such as the abscisic acid pathway and transcription factors. Of particular interest is a group of dehydrins quantified at both total protein and phosphopeptide levels, permitting insight into stoichiometry. The biological function of dehydrins in the model plant Arabidopsis thaliana is known to be regulated by phosphorylation. Conclusions: Translation of protein function from model plant to crops remains highly challenging because genome duplication has created complex sets of orthologous and homologous proteins. By focusing on proteomic changes during crop stress responses, this work enables the identification of known and novel proteins, substantially aiding the transfer of knowledge from model plants to crops. Full article

Reconstruction in head and neck surgery requires restoration of complex functions, including speech, swallowing, and breathing, while preserving as much facial form and patient identity as possible. Over the past decade, advances in preoperative digital planning, intraoperative technologies, and robotic platforms have reshaped reconstructive strategies, giving rise to the concept of hybrid reconstruction. Hybrid approaches integrate free tissue transfer with computer-aided design and manufacturing (CAD/CAM), virtual surgical planning, intraoperative navigation, and robot-assisted microsurgery to enhance precision, reproducibility, and functional outcomes. This narrative review examines the principles and applications of hybrid reconstruction in head and neck surgery with particular emphasis on osseous reconstruction of the mandible, maxilla, and midface. The roles of intraoperative navigation and robotic assistance as enabling tools are discussed, along with their potential benefits and current limitations. Functional and morphologic outcomes, patient-reported quality of life, and challenges related to cost, access, training, and evidence heterogeneity are critically reviewed. Hybrid reconstruction represents an advancement toward outcomes-driven, patient-centered care; however, thoughtful integration of emerging technologies and continued emphasis on rigorous outcome assessment are essential to guide responsible adoption in contemporary head and neck reconstructive surgery. Full article

Open-source bioprinting can broaden access to biofabrication, enabling existing systems to perform high-resolution tissue manufacturing. However, most of these focus on low cost, easy assembly, or specific biomaterial ink rather than making a robust standardized and modularized multifunction platform. In this study, we present CrystalCells, a user-friendly modular open-source bioprinting system centered on the TridentExtruder, a high-performance syringe extruder with extrusion/retraction capability and tool-free automated syringe coupling. The system enables the automated exchange of syringe, temperature-controlling, microscope, and pipette modules. Repeated syringe return-and-pickup cycles showed repositioning errors within ±20 μm, while the extruder generated pressures above 950 kPa and exhibited lower elastic deformation than the Replistruder 4 under the same pressure conditions. CrystalCells supported the extrusion of pre-crosslinked alginate, FRESH printing, and dual-biomaterial inks printing with automated exchange. A microscope module resolved stained HeLa cells and enabled layer-by-layer imaging for defect detection during printing. A thermoelectric module maintained the syringe barrel below 6 °C during the printing of an alginate–collagen biomaterial ink at 23 °C (room temperature), and a pipette module transferred 2–10 μL volumes with errors within ±0.5 μL. These results show that CrystalCells is an open-source modular biofabrication platform integrating printing, imaging, temperature control, and liquid handling within a single workflow. Full article

The walnut cultivar ‘Yunxin No. 14’ is an early fruiting, high-yielding, and widely adaptable fruit tree with compact growth and superior nuts. Establishing a successful tissue culture system for this cultivar is crucial for its rapid clonal propagation and as a foundation for future genetic transformation. Using young fruits as explants, 3% NaClO sterilization for 20 min effectively controlled contamination and browning. Somatic embryos induced from zygotic embryos cultured on DKW medium with 30 g·L⁻¹ sucrose showed high proliferation and minimal browning. After a 4-day dehydration treatment using saturated NH₄NO₃, mature somatic embryos germinated rapidly on differentiation medium (DKW containing 1 mg·L⁻¹ 6-BA and 0.1 mg·L⁻¹ IBA), reaching 90.0% germination. Optimal shoot multiplication was achieved on DKW medium supplemented with 2 mg·L⁻¹ 6-BA and 0.3 mg·L⁻¹ IBA, yielding a proliferation rate of 91.1% and a proliferation index of 3.1. For rooting, shoots (~3 cm) treated with Clonex^® rooting gel were transferred to a low-cost, sugar-free vermiculite medium with gaseous CO₂ as the sole carbon source. Root initiation occurred within two weeks at a rate of 54.2%, significantly shortening the rooting phase. Rooted plantlets were acclimatized in a peat:perlite:vermiculite (2:2:1, v/v/v) mixture under high humidity for two weeks before outdoor transfer, achieving an 88.6% survival rate. This study provides a reliable protocol for the micropropagation of ‘Yunxin No. 14’ and a valuable reference for other difficult-to-root woody species. Full article

Halide double perovskites with near-infrared (NIR) emission are promising for optoelectronic applications. NIR-II (1000–1700 nm) emission, in particular, is attractive due to its strong tissue penetration, high spatial resolution, and low biological light damage risk. However, materials capable of NIR-II emission often require additional sensitizers and suffer from issues such as narrow emission bandwidth and low photoluminescence efficiency. In this work, we report a Re⁴⁺ doping strategy using Cs₂WCl₆, a vacancy–ordered double perovskite, to achieve efficient NIR-II emission. Spectroscopic and dynamic measurements reveal energy transfer between the Cs₂WCl₆ matrix and the Re⁴⁺ centers, resulting in efficient broadband NIR-II emission centered at 1345 nm (FWHM ≈ 87 nm), along with broad excitation ranging from 250 to 850 nm. The optimal NIR-II emission occurs at 1345 nm with a photoluminescence quantum yield (PLQY) of 29.83% when the Re⁴⁺ doping concentration is 1%. This work demonstrates an efficient, sensitizer-free method for achieving broadband NIR-II emission and provides a new material strategy for high–performance double perovskites NIR light sources. Full article

Reconstruction of the ear and temporal region presents unique challenges due to the complex anatomy of the lateral skull base and the need to restore both structural integrity and auditory function. Historically managed as separate entities, auricular reconstruction and hearing rehabilitation are increasingly approached in an integrated manner, supported by advances in microsurgical techniques and implantable hearing technologies. This narrative review synthesizes contemporary evidence on microsurgical reconstruction of the ear and temporal region in conjunction with hearing rehabilitation, analyzing a wide range of existing surgical techniques in an integrative manner. Reconstructive techniques discussed include local and regional flaps, free tissue transfer, auricular framework reconstruction using autologous cartilage or alloplastic materials, external auditory canal reconstruction, and subtotal petrosectomy. Hearing rehabilitation options reviewed encompass bone-anchored hearing systems, active and passive transcutaneous devices, middle ear implants, and cochlear implantation. Simultaneous reconstruction and implantation may reduce surgical burden and enable earlier hearing restoration in carefully selected patients, while staged approaches remain advantageous in complex or high-risk scenarios, particularly in the presence of chronic infection or extensive temporal bone surgery. Multidisciplinary collaboration, meticulous preoperative planning, and long-term follow-up are essential to optimize outcomes. Full article

Organochlorine pesticides (OCPs), a broad class of highly stable and lipophilic chemicals, have been widely used to control pests and disease vectors in agriculture, households, and the public health sector. Due to their lipophilic nature and resistance to degradation, OCPs accumulate in the fatty tissues of fish and shellfish, positioning these foods as critical vectors for human exposure. This review synthesizes current global research on the presence of OCPs in fish and shellfish, with an emphasis on geographical variation, species-specific accumulation patterns, and temporal trends. This study discusses the sources and pathways which bring OCPs to the aquatic environment to highlight regional disparities in pollutant levels, influenced by industrial activities, agricultural practices, and waste management systems. It also explores the mechanisms of bioaccumulation and biomagnification that contribute to the elevated levels of OCPs in fish and shellfish, underscoring the complexities of food chain dynamics in contaminant transfer. This paper also highlights the diverse adverse effects of OCPs on consumer health, including chronic and carcinogenic diseases such as endocrine and respiratory malfunctions, neurotoxicity, kidney and liver damage, reproductive disorders, and skin or eye injuries, while suggesting mitigation strategies to promote an OCP-free and healthy aquatic environment. Full article

Background/Objectives: Locally advanced midface malignant tumors require extensive resection, resulting in complex defects involving bone and multiple soft tissue structures. Reconstructing these substantial defects presents a significant challenge to restore both function and aesthetics. This study aims to compare the functional and aesthetic outcomes of chimeric free flaps versus single free flaps in midface microvascular reconstructions. Methods: This retrospective analysis included fifty consecutive patients with Type III Cordeiro defects who underwent midface reconstruction with free tissue transfer between 2020 and 2024. The cohort included fourteen patients who received prefabricated chimeric flaps and thirty-six patients who received single free flaps. Outcomes were assessed six months postoperatively using a modified University of Washington Quality of Life Questionnaire (UW-QOL), analyzing domains including speech, chewing, sensation, appearance, pain, and social activity. Statistical analysis was performed using the Mann–Whitney U test. Results: In the chimeric flap group, no major flap necrosis or complications were observed. In unadjusted comparisons, the chimeric flap group showed higher transformed UW-QOL scores in several domains. Statistically significant between-group differences were observed for opening and speech (p = 0.004), change in appearance (p = 0.022), sensation (p = 0.011), and social activity (p = 0.006). Aesthetic outcomes, assessed via patient rating of appearance, were also significantly higher in unadjusted comparisons with the chimeric flap approach. Furthermore, in Type IIIa defects, titanium mesh successfully provided reliable orbital support. Conclusions: Chimeric free flaps represent a feasible reconstructive option in selected cases of complex maxillary and midface reconstruction. Their main advantages—providing the proper amount of specific, well-vascularized tissue and offering greater mobility of components— may be associated with more favorable functional, aesthetic, and social outcomes in unadjusted comparisons compared to reconstruction using single free flaps. Full article