Search Results (7,252)

Spinal cord injuries disrupt the motor, sensory, and autonomic functions routinely carried out by the spinal cord, with injury progressing from primary mechanical damage from the initial trauma to a secondary phase driven by inflammation and cellular cascades. This disruption significantly impacts the patient’s ability to perform basic physiological and voluntary functions seen in a normal spinal cord, which often results in long-term disability and dependence on supportive care. Stem cell therapies, including mesenchymal stem cells, neural stem cells, and induced pluripotent stem cells, have been investigated as potential regenerative approaches that may promote repair through neuroprotection, remyelination, and axonal regeneration. Preclinical studies have demonstrated encouraging results in motor and sensory recovery following injury; however, clinical evidence remains limited and variable. Some studies report improvements in motor and sensory function post-injury, with improvements in bladder and bowel management, tissue repair, and other functions. Overall, the outcomes vary based on cell type, delivery method, and the stage of spinal cord injury. The key challenges of stem cell therapy include safety concerns and the limited number of small-scale studies currently available. Additionally, understanding the variability in therapeutic outcomes and identifying optimal treatment conditions are critical steps toward advancing stem cell therapies in spinal cord injury repair. This review aims to characterize and summarize the stem cell approach to the treatment of spinal cord injuries, while also critically highlighting the limitations of current preclinical and clinical evidence, as well as the importance of continued investigation into the long-term and functional recovery processes and possibilities, as well as the patient’s quality of life following treatment with stem cells for spinal cord injury. Full article

TEA domain transcription factors are critical regulators of tissue development and regeneration in mammals, yet their roles in aquatic invertebrate regeneration remain poorly understood. Here, a full-length cDNA encoding a putative transcriptional enhanced associate domain protein 1 (TEAD1) ortholog in Apostichopus japonicus (AjTEAD1) was cloned and characterized. The open reading frame (ORF) of AjTEAD1 is 1344 bp, encoding a polypeptide of 447 amino acids with a conserved TEA domain (Asp⁴⁰–Leu¹¹¹) and a protein-binding domain (Gly²³¹–Asp⁴⁴⁶). Function analysis demonstrates that AjTEAD1 is essential for intestinal regeneration. AjTEAD1 expression was significantly upregulated during the regeneration process. Functional impairment of AjTEAD1 suppressed intestinal regeneration and attenuated cell proliferation. At the molecular level, we identified the cell cycle gene in A. japonicus (AjCyclin E), whose expression pattern coincided with that of AjTEAD1 and was downregulated following AjTEAD1 knockdown. Dual-luciferase reporter assays further confirmed that AjTEAD1 binds to specific sites in the AjCyclin E promoter and transcriptionally activates its expression. In summary, our study reveals that AjTEAD1 promotes cell proliferation and drives intestinal regeneration in A. japonicus by directly upregulating AjCyclin E transcription. These findings identify the TEAD–Cyclin E axis as a key regulator of echinoderm regeneration, shedding new light on the regenerative processes and cytological mechanisms in economically important species. Full article

Peripheral nerve injuries involving critical-sized gaps remain a major clinical challenge. Although autologous nerve grafting is considered the gold standard for peripheral nerve repair, its clinical application is limited by the availability of donor nerve tissue and the risk of donor-site morbidity, including sensory deficits and functional impairment. Therefore, nerve guidance conduits (NGCs) have emerged as a promising alternative when combined with bioactive modulation strategies. In this study, we evaluated bisvinyl sulfonemethyl (BVSM)-crosslinked gelatin conduits integrated with electrical stimulation (ES) at different frequencies (0, 2, 20, and 200 Hz) in a rat sciatic nerve defect model over a 4-week recovery period (n = 10 per group). Structural regeneration was assessed by morphometric analysis, electrophysiology, macrophage infiltration, CGRP immunoreactivity, retrograde Fluorogold tracing, quantitative PCR of growth factors and inflammatory cytokines, and behavioral testing. Among all stimulation paradigms, low-frequency ES at 2 Hz produced the most pronounced regenerative effects. The 2 Hz group demonstrated significantly greater axon number, axonal density, and regenerated nerve area compared with control and high-frequency groups (p < 0.05). Electrophysiological assessments revealed improved nerve conduction velocity, higher MAP amplitudes, and shorter latencies. Enhanced macrophage recruitment and elevated CGRP expression were observed, suggesting coordinated neuroimmune and neurochemical activation. Gene expression analysis indicated upregulation of neurotrophic factors and balanced inflammatory cytokine responses under low-frequency stimulation. In contrast, high-frequency stimulation (200 Hz) failed to enhance overall regeneration and showed reduced axonal metrics, suggesting possible overstimulation-associated suppression. Collectively, these findings demonstrate that BVSM-crosslinked conduits provide a stable and biocompatible regenerative scaffold, and that appropriately tuned low-frequency electrical stimulation (2 Hz) optimally enhances structural, molecular, and functional recovery. The integration of material engineering with bioelectrical modulation represents a promising strategy for next-generation bioelectronic interfaces in peripheral nerve repair. Full article

As natural nanoscale intercellular messengers, exosomes exhibit considerable potential in modulating inflammation, angiogenesis, immunoregulation, and tissue remodeling, making them attractive candidates for regenerative medicine. However, their clinical translation remains limited by rapid systemic clearance, nonspecific biodistribution, insufficient lesion retention, and functional attenuation in hostile pathological microenvironments. In this review, we propose that biomaterial engineering should evolve from providing passive exosome carriers to constructing active regulatory platforms capable of precise spatiotemporal control. We summarize engineering strategies along two complementary dimensions. In the temporal dimension, biomaterials can enable sustained, sequential, or microenvironment-responsive release to match the dynamic phases of tissue repair. In the spatial dimension, biomaterials can improve local retention, tissue anchoring, structural guidance, endogenous cell recruitment, and lesion-specific delivery. Using cutaneous wound healing, osteochondral regeneration, myocardial repair, and neural regeneration as representative examples, we further analyze these strategies through a “clinical challenge–engineering strategy–biological mechanism” framework, with particular attention to how engineered systems influence key signaling pathways such as PI3K/Akt, Wnt/β-catenin, NF-κB, and PTEN/PI3K/Akt/mTOR. We also discuss translational barriers, including exosome heterogeneity, safety concerns inherited from parental cells, large-scale GMP-compliant manufacturing, product standardization, storage stability, and regulatory classification of exosome–biomaterial hybrids. Finally, we highlight emerging directions, including multi-mechanism combinational systems, closed-loop responsive platforms, and artificial intelligence-assisted design for personalized exosome therapeutics. This review provides a design-oriented framework to accelerate the bench-to-bedside development of biomaterial-enabled precision exosome therapy. Full article

Background/Objectives: Zebrafish fin regeneration serves as a classic model for investigating vertebrate tissue regeneration, yet the core regulatory networks and their crosstalk with the immune microenvironment remain incompletely characterized. This study aimed to identify hub genes, and elucidate the underlying molecular mechanisms and immune microenvironment dynamics during zebrafish fin regeneration. Methods: We integrated multiple bulk RNA-seq datasets of zebrafish fin regeneration from the GEO database, followed by data standardization with batch effect removal. Hub genes were screened via differential expression analysis, weighted gene co-expression network analysis (WGCNA), and predictive models constructed with 13 classic machine learning algorithms. Functional enrichment, time-ordered gene co-expression network (TO-GCN) method, immune infiltration analyses and RT-qPCR validation were further performed. Results: We identified upregulated differentially expressed genes, regeneration-correlated gene modules and their overlapping genes, including 82 candidate genes and 10 hub genes enriched in cytoskeleton remodeling, extracellular matrix organization, and focal adhesion. Temporal analysis uncovered hierarchical gene regulation and functional switching during regeneration. Hub gene expression was significantly correlated with the infiltration of B cells, M1/M2 macrophages and CD8+ T cells, revealing a stage-specific immune microenvironment. RT-qPCR validation showed high consistency with the multi-omics data. Conclusions: This study provides potential gene targets for understanding zebrafish fin regeneration, and offers a valuable reference for investigating the crosstalk between regulatory networks and the immune microenvironment in vertebrate tissue regeneration. Full article

The manuscript details the influence of high-temperature and high-shear processing, as well as radiation sterilization, on properties of bioresorbable and osteoconductive, patient-tailored alloplastic scaffolds for guided bone regeneration. Functionalized poly(l-lactide-co-d,l-lactide) copolymer filled with hydroxyapatite was used to produce two personalized implants for upper and lower jaw reconstruction via 3D printing. Morphology analysis (SEM, µCT), gel permeation chromatography, and thermal analysis quantified the effects of melt processing and sterilization on chain structure. Physical properties of sterilized parts, such as hardness and density, proved suitable for bone implants. Removal of the upper jaw implant after 4 months and of the lower jaw substitute after 18 months enabled monitoring of bioresorption and tissue regrowth over time. Gradual overgrowth of the implants with human tissue, initiated by the osteoconductive filler, was observed, along with time-dependent polylactide degradation, showing up to 92% molar mass reduction. The medical procedures confirmed safety, nontoxicity, non-allergenicity, and, most importantly, the tissue-forming properties of the polylactide-based formulation. Full article

Premature ovarian insufficiency (POI) is a clinical condition characterized by loss of ovarian function indicated by amenorrhea or irregular menstrual cycles for at least 4 months and elevated gonadotrophins (FSH > 25 IU/L, measured on one occasion) and low estrogen serum levels in women under the age of 40. Premature ovarian insufficiency can be non-iatrogenic or spontaneous (idiopathic or due to genetic, autoimmune, or metabolic reasons, or infections) and iatrogenic (a consequence of oophorectomy, chemotherapy, radiotherapy, or uterine artery embolization). Women with POI are faced not only with estrogen deficiency but also with infertility and psychological implications. Hormonal replacement therapy is effective in treating the symptoms of premature ovarian insufficiency as well as in lowering the health risk of long-term consequences of premature ovarian insufficiency. Currently, oocyte donation is the standard treatment for patients with POI desiring pregnancy. Recently developed methods for the regeneration of ovarian tissue, such as stem cell therapy, platelet-reach plasma therapy and in vitro activation of ovarian tissue, are still under research and further adequate multicentric clinical studies are needed to develop standardized effective and safe protocols for the infertility treatment of patients with premature ovarian insufficiency. Full article

Wound-healing and skin regeneration are the focus of intensive research, driven by a rapidly expanding global market and the growing clinical demand for more effective interventions engineered to actively direct and enhance tissue regeneration. Recent advances in biomaterial engineering and 3D bioprinting have accelerated the development of highly customized, functional constructs mimicking native tissue. Together, these innovations are reshaping therapeutic strategies and expanding the translational potential of next-generation skin substitutes. This review presents an overview of the evolution of material printing technologies and the different categories of 3D bioprinting techniques and processing methods, followed by an evaluation of the properties of natural biomaterials as bioinks for skin wound-healing and their application in skin tissue engineering. Moreover, we provide a comprehensive global market analysis, with consideration of costs, benefits, and a SWOT analysis to identify the full potential of this technology for the development of novel skin wound-healing products. Recommendations and future perspectives are provided to guide researchers, clinicians, and industry partners on the current state and potential of adopting 3D bioprinting with natural biomaterials for effective wound-healing therapies. Full article

The utilization of immunomodulatory nanomaterials, i.e., leveraging their unique properties to enhance immune responses, represents a transformative approach for the treatment of various diseases. Recent advancements in nanotechnology have enabled the design of nanomaterials capable of delivering immunomodulatory agents in a targeted manner, such as cytokines, antibodies, and nucleic acids, to specific cells or tissues involved in immune regulation. These nanomaterials, including nanoparticles, liposomes, nanogels, nanoemulsions, dendrimers, MXenes and extracellular vesicles, have been increasingly tailored to modulate immune responses with precision and efficacy. This targeted approach not only enhances therapeutic outcomes but also reduces off-target effects, minimizing systemic toxicity. In this review, an overview of immunomodulatory nanomaterials and their biomedical applications are highlighted. Herein, we have discussed different types of nanomaterials and their design strategies, interactions with different immune system components (macrophages, dendritic cells (DCs), neutrophils, T lymphocytes (CD4⁺ helper T-cells, CD8⁺ cytotoxic T-cells, regulatory T-cells/Tregs, and memory T-cells), and B lymphocytes), and immunomodulation mechanisms. Furthermore, nanomaterial-based immunomodulation strategies to enhance cancer immunotherapy, wound healing, and bone regeneration and the treatment of infectious diseases, autoimmune diseases, and allergy and are discussed in detail. In addition to therapeutic applications, selected nanomaterial platforms demonstrate significant potential in pharmaceutical formulations by improving drug stability, controlled release, and bioavailability, as well as in cosmetology through skin-targeted delivery, anti-inflammatory activity, immune protection, and enhanced tissue regeneration. Finally, clinical trial updates, challenges and future prospects are outlined. Key findings indicate that lipid-based, polymeric, inorganic nanoparticles and dendrimers provide complementary advantages for immunomodulation, including efficient delivery, controlled release, multifunctionality, and precise immune targeting. Despite safety, regulatory, and scalability challenges, these systems show strong potential for advancing precision and personalized medicine. Taken together, these innovations hold great promise for personalized medicine approaches, wherein nanomaterials can be tailored to individual patient profiles for more effective and precise disease treatment and prevention strategies. This review focuses primarily on the mechanistic interactions between immunomodulatory nanomaterials and immune cells, including macrophages, dendritic cells, neutrophils, T lymphocytes, and B lymphocytes, rather than providing an exhaustive treatment of physicochemical optimization parameters such as particle size or surface modification chemistry, which fall outside the defined scope of this work. Full article

Nanotheranostic platforms integrating diagnostic and therapeutic functions within a single system have attracted significant attention in precision medicine. However, conventional nanotheranostics based on systemic administration often suffer from off-target accumulation, limited retention at disease sites, and dose-limiting toxicity. To address these limitations, hydrogel-integrated nanotheranostic systems have emerged as a promising strategy for achieving localized diagnosis and therapy with improved spatial control and safety. This review provides a comprehensive overview of recent advances in hydrogel–nanomaterial nanotheranostic platforms, focusing on their design principles, diagnostic capabilities, and therapeutic applications. We discuss the complementary roles of hydrogels and nanomaterials, where hydrogels function as localized reservoirs and tissue interfaces, and nanomaterials provide imaging and therapeutic functionalities. Key integration strategies including physical encapsulation, chemical conjugation, and in situ nanoparticle formation are systematically compared. We further summarize localized diagnostic modalities such as real-time imaging and therapy monitoring, and highlight research-driven applications in cancer treatment, inflammation and infection management, and tissue regeneration. Finally, major translational challenges and future perspectives toward personalized, image-guided local theranostics are discussed. Overall, hydrogel-based nanotheranostic platforms represent a versatile approach for next-generation localized precision medicine. Full article

Bone tissue plays a vital role in the human body and possesses intrinsic self-repair mechanisms; however, large defects or pathological fractures may exceed its natural healing capacity. Bone tissue engineering provides promising strategies to restore bone integrity through the use of scaffolds, growth factors, and stem cells. While calcium phosphate (CaP)-based ceramics, such as hydroxyapatite (HAp) and tricalcium phosphate (TCP), represent the current benchmark, their limitations, including slow degradation (HAp) and limited osteoinductivity (TCP), have driven the development of alternative biomaterials. In this context, magnesium phosphate (MgP)-based materials have gained increasing attention due to their tunable resorption rate, improved biodegradability, and ability to stimulate osteogenesis and angiogenesis through the release of magnesium (Mg²⁺) ions. This study reports on composite scaffolds based on electrospun poly(ε-caprolactone) (PCL) fibres coated with MgP layers doped with lithium (Li) and zinc (Zn), designed to mimic the nanofibrous architecture of the extracellular matrix. Lithium and zinc were selected due to their known ability to modulate cellular response, with lithium promoting osteogenic activity and zinc contributing to improved cell proliferation and antibacterial potential. The phosphate phases obtained by coprecipitation were deposited onto the PCL fibres using Matrix-Assisted Pulsed Laser Evaporation (MAPLE), enabling controlled surface functionalization. Following thermal treatment, the formation of the crystalline magnesium pyrophosphate (Mg₂P₂O₇) phase was confirmed by chemical and structural characterization. The combination of a slowly degrading PCL matrix, providing sustained structural support, and a bioactive MgP coating, enabling rapid and controlled ion release, results in improved scaffold performance in terms of biocompatibility, biodegradability, and bioactivity. While the slow degradation rate of PCL ensures mechanical stability over an extended period, the surface-deposited MgP phase allows immediate interaction with the biological environment, facilitating faster ion release and enhancing cell–material interactions. These findings highlight the potential of the developed composites as promising candidates for trabecular bone regeneration and as viable alternatives to conventional CaP-based scaffolds in regenerative medicine. Full article

Hair loss, particularly androgenetic alopecia (AGA) and alopecia areata (AA), is a prevalent condition with widespread psychosocial impact. Recently, low-level laser therapy (LLLT) has emerged as a promising non-invasive therapeutic alternative due to its bioregulatory effects and favorable safety profile compared to conventional pharmacological treatments. In this study, we employed fluorescence lifetime imaging microscopy (FLIM) to investigate the effects of red-light irradiation on hair follicle dynamics and the cutaneous microenvironment in a C57BL/6 mouse model. A hair regeneration model was established to evaluate the efficacy of 650 nm red-light irradiation (bandwidth ± 20 nm). Then, the skin tissue was stained with hematoxylin and eosin (H&E) and followed by FLIM analysis to provide a multidimensional assessment of tissue morphology and metabolic status. Results showed that red-light irradiation significantly increased hair follicle numbers and enhanced adenosine triphosphate (ATP) levels in the skin tissue. FLIM analysis further revealed prolonged fluorescence lifetime values across different epidermal and dermal layers in the irradiated group, indicating significant alterations in the skin metabolic microenvironment. Furthermore, phasor plot analysis enabled precise differentiation between hair follicles and their surrounding skin structures, highlighting FLIM’s high sensitivity and accuracy in evaluating hair growth. In conclusion, this study has provided novel imaging-based insights into the mechanisms of LLLT-induced hair regeneration, highlighting the potential of FLIM as a powerful tool for characterizing the cutaneous microenvironment and quantitatively evaluating phototherapeutic efficacy in future translational applications. Full article

Modern dentistry increasingly relies on light-curing units (LCUs) and lasers in essential clinical procedures such as composite resin polymerization, caries treatment, and periodontal therapy. This review aims to outline the evolution of light-emitting technologies and to assess their potential biological risks, with particular emphasis on effects on the visual system, oral tissues, and microbiome. The development of curing devices is presented chronologically, from the first-generation ultraviolet (UV-A) lamps introduced in the 1970s to current light-emitting diode (LED-LCU) systems and dental lasers (e.g., Er:YAG, Nd:YAG). The progressive increase in light intensity—now exceeding 3000 mW/cm²—has shortened curing times but simultaneously raised safety concerns. Major hazards include the so-called blue-light hazard, where exposure to high-energy visible (HEV) blue light may accelerate macular degeneration, and temperature elevations in the pulp chamber, which may damage the dentin–pulp complex. Laser radiation also exerts significant microbiological effects: Er:YAG and diode lasers demonstrate bactericidal activity against biofilms and oral pathogens (e.g., P. gingivalis), although therapeutic outcomes depend on wavelength, dose, and exposure time. Suboptimal parameters may lead to microbiome disturbances, whereas low-level laser therapy (LLLT; 600–1200 nm) supports tissue regeneration and helps restore microbial balance. The individualization of irradiation parameters, combined with thorough theoretical knowledge, operator expertise, and technical understanding of LCUs and lasers, is essential for maximizing clinical benefits while minimizing health risks and preserving oral microbiome homeostasis. Full article

Plant-derived exosomes (PDEs) are gaining attention owing to their key implications in cross-kingdom communication, facilitating bioactive entities among plants and animals. PDEs are tiny nanoscale vesicles generally comprised of RNAs, proteins, and secondary metabolites and are involved in the regulation of physiological processes (immune modulation, cell regeneration, and stress response). An important feature of PDEs is to enable cross-kingdom regulation in skin wound repair. This is because PDEs can modulate several signaling pathways (PI3K-Akt, TGF-β, and mitogen-activated protein kinase) that further direct inflammatory, cell migratory, angiogenic, and extracellular matrix remodeling. Key features of PDEs, including modest immunogenicity, easy crossing of biological barriers, and natural biocompatibility, make them novel alternatives to synthetic wound-healing agents. Therefore, this review disparagingly examines the biogenesis, molecular composition, and diversified biological functions of PDEs, particularly with reference to potential implications in wound healing and overall skin health. The current challenges pertaining to PDE isolation, scalability, and bioavailability and regulatory hurdles for their clinical translation were also explored. In addition, the epigenetic effects of PDEs on human skin cells and wound healing are explained in detail. Finally, this review presents a comprehensive investigation of PDEs in skin wound repair, identifies research gaps, and outlines future directions for dermatological applications. Full article

The increase in older adults and active lifestyles has made chondral and osteochondral lesions common in the population, making them one of the central challenges in orthopedics. Although hydrogel-based regenerative medicine offers an encouraging therapeutic option for these lesions, important obstacles still prevent these therapies from reaching the clinic. In view of these factors, we adopted a risk-based approach for this review, in line with the current legislative requirements in clinical translation and clinical trials. We identified the factors that could undermine patient safety or lead to poor outcomes. Then, we outlined solutions to remedy these problems that integrate hydrogel technology, clinical/pharmaceutical/surgical protocols, and post-operative follow-up. Upcoming studies should give priority to the development of hydrogel scaffolds modified to mimic cartilage’s mechanical and physicochemical properties, together with patient-specific features. Other crucial characteristics are host-tissue integration, long-lasting cartilage tissue regeneration, and a positive outcome. In parallel, to scale complex and costly innovations, efforts should focus on a harmonized, simplified legislative landscape, optimized standards, and established follow-up protocols. Getting through this “valley of death” between research and innovation is strategic for reaching the clinics and the largest number of patients. Full article