Temporomandibular joint (TMJ) disorders represent chronic degenerative musculoskeletal conditions with a high prevalence in the general population and limited regenerative treatment options. Owing to the insufficient efficacy of current conservative and surgical therapies, there is a growing clinical need for biologically based regenerative approaches. Tissue engineering (TE), particularly scaffold-based strategies, has emerged as a promising avenue for TMJ regeneration. This systematic review analyzed preclinical in vivo studies investigating scaffold-based interventions for TMJ disc and osteochondral repair. A structured literature search of PubMed and Scopus databases identified 39 eligible studies. Extracted data included scaffold composition, use of cellular and bioactive components, animal models, and reported histological, radiological, and functional outcomes. Natural scaffolds, such as decellularized extracellular matrix and collagen-based hydrogels, demonstrated favorable biocompatibility and support for fibrocartilaginous regeneration, whereas synthetic materials including polycaprolactone, poly (lactic-co-glycolic acid), and polyvinyl alcohol provided superior mechanical stability and structural tunability. Cells were used in 17/39 studies (43%); quantitative improvements were variably reported across these studies. Bioactive molecule delivery, including transforming growth factor-β, histatin-1, and platelet-rich plasma, further enhanced tissue regeneration, while emerging drug- and gene-delivery approaches showed potential for modulating local inflammation. Despite encouraging results, the reviewed studies exhibited substantial heterogeneity in experimental design, outcome measures, and animal models, limiting direct comparison and translational interpretation. Scaffold-based approaches show preclinical promise but heterogeneity in design and incomplete quantitative reporting limit definitive conclusions. Future research should emphasize standardized methodologies, long-term functional evaluation, and the use of clinically relevant large-animal models to facilitate translation toward clinical application. However, functional and biomechanical outcomes were inconsistently reported and rarely standardized, preventing robust conclusions regarding the relationship between structural regeneration and restoration of TMJ function.

Nanoparticles have become an essential platform for next-generation drug delivery and therapeutic development, yet clinical translation remains limited by an incomplete understanding of their interactions within human biological systems. Organ-on-a-chip technology offers a powerful approach to evaluate efficacy and safety of nanomedicine under physiologically relevant conditions in human cells by recreating fluid flow, mechanical stress, barrier function, immune interactions and inter-organ communications. These advanced in vitro systems allow quantitative assessments of nanoparticle transport, distribution, and safety with improved human relevance compared to conventional cell culture and animal models. The integration of sensors within organ-on-a-chip platforms enables real-time monitoring of tissue responses and nanoparticle kinetics. Advances in automation and robotic liquid handling support scalable and reproducible testing across multiple tissue models. Artificial intelligence and active learning tools facilitate automated data analysis and experimental optimization, paving the way towards self-driving nanomedicine evaluation platforms that accelerate discovery and clinical translation.

Onychomadesis, characterized by proximal detachment of the nail plate due to temporary arrest of matrix proliferation, has been increasingly recognized as a complication following viral infections. Enterovirus-associated hand-foot-and-mouth disease (HFMD) is the most frequently reported cause. Recent studies demonstrate that some enteroviruses, including Coxsackievirus A10, utilize the host receptor KREMEN1 (KRM1) to impair Wnt/β-catenin signaling and suppress nail stem cell differentiation, thereby providing a molecular basis for infection-induced nail shedding. Additionally, cases of onychomadesis linked to other viral infections, including KRM1-independent enteroviruses, influenza virus, SARS-CoV-2, varicella-zoster virus, and co-infections involving HIV and mpox, have also been documented. Despite growing recognition of the virus-induced onychomadesis, in most cases the exact pathogeneses are yet elusive, thereof lack of approved treatments. Understanding the molecular mechanisms of onychomadesis and other sequelae can enhance diagnostics and therapies, guiding future drug development for virus-induced nail disorders and related complications. A comprehensive literature search was conducted using PubMed up to Dec 2025, including the search terms: onychomadesis, Beau's line, infection or virus, and follow-up. This review aims to explore the molecular pathophysiology of virus-induced onychomadesis and to examine the underlying molecular mechanisms, including the roles of viral receptors and signaling pathways in nail stem cell differentiation. It scrutinizes the currently available literatures of link between viral infections, particularly HFMD, and onychomadesis, focusing on the molecular mechanisms involved, and explores potential therapeutic insights.

Background Cell-based therapies are revolutionizing medicine by offering regenerative and immunomodulatory capabilities beyond traditional treatments. These therapies hold promise for diseases such as cancer, autoimmune disorders, and diabetes. However, clinical translation is challenged by immune rejection, reduced cell viability, and poor control over therapeutic delivery. Summary Biomaterials can provide innovative solutions to these barriers by creating supportive environments, enhancing cell survival, and enabling targeted, sustained delivery. This review highlights advances in biomaterial strategies-including lipid and polymeric nanoparticles, hydrogels, fibrous scaffolds, and layer-by-layer assemblies-and their application across T-cell, macrophage, stem cells, and islet cell therapies. Each material class offers unique physicochemical and/or mechanical properties that can be tuned to meet the specific needs of different cell types and therapeutic contexts. Key Messages Biomaterials provide critical tools for enhancing the efficacy and precision of cell-based therapies. Despite substantial progress, challenges remain with selecting the appropriate biomaterial for specific applications and retaining biocompatibility long term. The ongoing development of patient-specific and adaptable biomaterials holds promise for further breakthroughs in regenerative medicine. This review underscores the potential of biomaterials to drive forward the field of cell therapy, opening new avenues for treating a wide range of diseases.

With each replication cycle, telomeres shorten. Telomerase can slow or reverse the rate of telomere shortening. In the era of cancer immunotherapy, telomerase is a promising tumor-associated antigen due to its widespread and specific expression in cancer cells and its strong immunogenicity. Interestingly, telomerase-based vaccines eradicate telomerase-expressing cancer cells by increasing antigen-specific T-cell responses rather than by directly inhibiting telomerase enzymatic activity as telomerase inhibitors function. To support this, telomerase-based vaccines, including DNA, mRNA, peptide-, and cell-based vaccines, have been evaluated in clinical settings to elucidate their molecular mechanisms of action. The aim of this review is to present the clinical effectiveness of telomerase vaccines alone or in combination with immunotherapy. In particular, the therapeutic effectiveness of telomerase vaccines is influenced by the tumor microenvironment and can be substantially increased by combining them with immune checkpoint inhibitors. To further optimize telomerase-based vaccines, we discuss translational challenges and highlight the need for further optimization.

Acute myeloid leukemia (AML) continues to pose significant therapeutic challenges, with high relapse rates driven largely by leukemic stem cells (LSCs), a rare, therapy-resistant population with self-renewal capacity, niche adaptation, and the ability to re-initiate disease. In this state-of-the-art review, we synthesize recent advances in LSC biology, addressing (i) how LSCs differ functionally and phenotypically from normal hematopoietic stem cells (HSCs), (ii) practical approaches for LSC quantification using multiparameter flow cytometry and LSC-enriched marker panels, (iii) the dysregulated signaling, metabolic and epigenetic programs that enable LSC persistence under chemotherapy and contribute to measurable residual disease, and (iv) current therapeutic strategies targeting LSC eradication, including antibody-based therapies, apoptosis and metabolic inhibitors, and emerging epigenetic agents. We also examine the key translational barriers, particularly antigen overlap with normal progenitors, microenvironmental protection, and the need for assay harmonization, while proposing a practical framework for integrating LSC assessment into risk stratification and therapeutic development.

Cancer remains one of the most prominent global health concerns, posing a substantial threat to public health. Millions of people die from cancer each year, and many cancer types remain incurable at present. Conventional cancer treatments, including surgery, chemotherapy, radiotherapy, and immunotherapy, often fail to achieve optimal clinical outcomes and are frequently associated with severe trauma and adverse effects. Consequently, there is an urgent need to develop novel therapeutic strategies to address these limitations. Hydrogels have been widely utilised as platforms for loading drugs, proteins, DNA, and stem cells in biomedical tissue repair and cancer therapy. Through modification of their physicochemical properties and functions, hydrogels can be endowed with responsiveness to multiple stimuli. In recent years, stimuli-responsive hydrogels (also known as smart-responsive hydrogels), as novel drug delivery systems, have demonstrated remarkable efficacy in cancer treatment. Stimuli-responsive hydrogels are capable of altering their mechanical properties, swelling behaviour, hydrophilicity, bioactivity, and molecular permeability in response to endogenous stimuli (including pH, ROS, and temperature) and exogenous stimuli (including light, ultrasound, and magnetic fields). This review highlights recent advances and applications of responsive hydrogels triggered by endogenous stimuli (including pH, ROS, and temperature) and exogenous stimuli (including light, ultrasound, and magnetic force) in cancer drug delivery and treatment. Finally, the current application limitations and future prospects of smart-responsive hydrogels are summarised.

Autoimmune ocular surface diseases represent a complex group of disorders in which systemic immune dysregulation triggers chronic inflammation, epithelial dysfunction, and progressive tissue fibrosis. Systemic lupus erythematosus, primary Sjögren's syndrome, and ocular cicatricial pemphigoid are the principal entities linking systemic autoimmunity to ocular surface pathology. These conditions share convergent mechanisms-including dysregulated cytokine signaling (IFN-I, IL-6, and IL-17), complement activation, and epithelial-mesenchymal transition-culminating in tear film instability and visual impairment. Recent advances in molecular immunology and omics profiling have elucidated disease-specific pathways and identified actionable therapeutic targets. Conventional immunosuppressants such as corticosteroids and cyclosporine remain fundamental, yet emerging biologics targeting BAFF, IFNAR, and JAK/STAT signaling-alongside regenerative strategies employing mesenchymal and induced pluripotent stem cells-are transforming disease management. Parallel innovations in amniotic membrane transplantation, keratoprosthesis, and bioengineered corneal scaffolds integrate structural reconstruction with immune modulation. Furthermore, the convergence of multi-omics analytics, artificial intelligence-assisted diagnostics, and microbiome-based immunomodulation heralds a new era of precision ophthalmology. This review synthesizes current molecular insights, clinical observations, and translational advances that collectively redefine autoimmune ocular surface diseases-from chronic inflammatory disorders into a targetable, regenerative, and potentially reversible spectrum of conditions.

Neural stem cells (NSCs) are self-renewing, multipotent cells of the central nervous system (CNS) that can differentiate into a range of specialized cell types, including neurons, astrocytes, and oligodendrocytes (OLs). Due to their remarkable ability to self-renew and differentiate, NSCs hold immense potential for the treatment of neurodegenerative diseases (NDDs). However, clinical translation remains hindered by challenges such as expansion difficulties and phenotypic drift. This review synthesizes evidence on the divergent effects of microgravity on NSC biology. While real spaceflight has been shown to enhance NSC proliferation, it paradoxically reduces neurosphere volume. Microgravity simulations yield contrasting results: rotating wall vessel (RWV) systems promote neuron and astrocyte generation, whereas rotating cell culture systems (RCCSs) inhibit differentiation despite the use of pro-differentiation media. These phenotypic variations critically depend on experimental conditions, cell sources, and observation time. Future research should focus on elucidating cross-pathway interactions and optimizing culture parameters to enable clinical-scale NSC applications.

Glioblastoma (GBM) remains one of the most lethal brain tumors, largely due to the resilience and plasticity of glioblastoma stem cells (GSCs), which drive tumor growth, recurrence, and resistance to conventional therapies. A key mechanism underlying their aggressiveness is transdifferentiation, whereby GSCs acquire endothelial- and pericyte-like phenotypes, promoting neovascularization and remodeling the tumor microenvironment to sustain malignancy. Conventional treatments often fail to eliminate these resilient populations, highlighting the need for innovative targeted strategies. Chimeric antigen receptor (CAR)-based immunotherapies offer a targeted strategy to specifically eliminate GSCs and interfere with their role in promoting tumor vascularization and suppressing immune responses. This review aims to provide a comprehensive overview of the molecular mechanisms driving GSC transdifferentiation and to summarize the current landscape of CAR-T therapies developed to target these cells. By integrating knowledge of GSC biology with advances in CAR-T-based interventions, this work highlights the potential of next-generation immunotherapies to overcome therapeutic resistance, limit tumor recurrence, and improve clinical outcomes in GBM.

Targeting the Warburg effect (aerobic glycolysis) in tumor cells represents a promising metabolic therapeutic strategy in cancer research. This review analyzes the regulatory mechanisms and therapeutic potential of key glycolysis pathway components, including glucose transporters (GLUTs) and glycolytic enzymes such as hexokinase 2 (HK2), phosphofructokinase (PFK), glyceraldehyde-3-phosphate dehydrogenase (GAPDH), pyruvate kinase M2 (PKM2), and lactate dehydrogenase A (LDHA). We evaluate the molecular mechanisms of various inhibitors and the current clinical development landscape, noting that limitations of monotherapy stem not only from tumor metabolic plasticity but also largely from the unacceptable toxicity of many inhibitors due to the essential role of glycolysis in normal cell metabolism. Furthermore, we explore the molecular basis of synergistic interactions between glycolysis inhibitors and chemotherapy, radiotherapy, immunotherapy, photothermal therapy, and targeted therapy, proposing that rational combination strategies may help overcome resistance and improve therapeutic efficacy. Finally, the review outlines future challenges and directions, emphasizing that the primary obstacle in metabolic treatments is achieving selective inhibition of glycolytic enzymes in cancer cells while sparing normal cells. To address this challenge, the development of high-selectivity agents, cancer-specific nanodelivery systems, precise biomarker identification, and innovative combination regimens based on metabolic-immune regulation is crucial for advancing glycolysis-targeted therapy toward clinical translation.

Acute myeloid leukemia (AML) is a biologically heterogeneous and clinically aggressive hematologic malignancy defined by the clonal expansion of immature myeloid progenitors, resulting in progressive bone marrow (BM) failure, peripheral cytopenias, and fatal infectious or hemorrhagic sequelae. The adverse clinical outcomes associated with AML arise from the combined effects of disrupted physiological hematopoiesis, persistence of therapy-refractory leukemic stem cells (LSCs), and extensive inter- and intratumoral genetic and epigenetic heterogeneity that underlies rapid disease progression and relapse. AML constitutes a prototypical disorder of hematopoietic dysregulation, wherein aberrant self-renewal capacity and arrested differentiation programs drive malignant transformation through the integrated influence of recurrent genomic lesions, epigenetic reprogramming, metabolic alterations, dysregulated signaling cascades, and reciprocal interactions with the BM microenvironment. These processes collectively reconfigure transcriptional landscapes and cellular hierarchies within the leukemic compartment. The objectives of this review are to provide an integrated framework for understanding AML pathobiology encompassing chromosomal abnormalities, transcriptional and epigenetic regulatory networks, and microenvironmental cues and to emphasize emerging analytical paradigms, including integrative multi-omics, single-cell and spatial technologies, and system-level approaches, which are reshaping conceptual models of malignant hematopoiesis and accelerating the development of mechanism-based therapeutic strategies.

The long-lasting, varied, and complicated nature of immune system issues in autoimmune disorders continues to make treatment difficult. Although standard immunosuppressive and biologic therapies have enhanced disease management, they infrequently provide enduring remission and often result in cumulative damage. Due to this, stem cell treatment has emerged as a potential alternative that aims to restore immunological homeostasis rather than maintain long-term immune suppression. This editorial review provides a comprehensive overview of the current evidence, unmet requirements, and future directions in the field, summarizing the primary contributions of the Special Issue "Stem Cell Therapy for Autoimmune Diseases". We examine the conceptual distinction between immune reset, as demonstrated by hematopoietic stem cell transplantation, and immune modulation, which is facilitated by mesenchymal stromal cells and their secretome. Systemic sclerosis, neuroimmunological disorders, inflammatory bowel disease, and type 1 diabetes exhibit disease-specific clinical experiences that underscore both context-dependent limitations and therapeutic potential. Meanwhile, an urgent need to address persistent issues such as incomplete immune reconstitution, autoreactive memory cell-driven relapse, a lack of predictive biomarkers, safety concerns, and complex ethical and regulatory problems is addressed. This review concludes by offering perspectives on the future development of this approach, highlighting standardization, biomarker-driven patient selection, and next-generation techniques, including extracellular vesicles and genetically modified cells. This overview marks stem cell therapy as a crucial area of research for the treatment of autoimmune disorders.

The achievements of regenerative medicine are based on methods of controlling stem cell division and differentiation. Electromagnetic fields stimulate cell differentiation by means of affecting calcium channels and cellular signaling. However, only a small part of the mechanisms underlying electromagnetic field effect on cells has been studied. The prospect of their use in tissue engineering as an addition or alternative to biochemical effects becomes clear in the course of numerous experiments. Electromagnetic stimulation enhances the effect of biochemical differentiation inducers and can cause the secretion of exosomes of special properties, which may serve as a therapeutic tool. For example, it has been shown that EMFs at 15 Hz and 2 mT increased the expression of chondrogenic differentiation markers SOX9 and COL2 in human bone-marrow MSCs by up to 3-fold (based on Parate et al.). Optimizing EMF parameters (e.g., 15-50 Hz, 1-2 mT) for specific cells and pathologies remains a key challenge of the studies in the field of tissue engineering. This review describes the electromagnetic field effect on the chondrogenic and osteogenic differentiation of MSCs of various origins, which is important for the musculoskeletal tissue recovery, as well as on inflammatory diseases in model animals.

The Hippo pathway plays a critical role in maintaining tissue homeostasis, regulating organ size, and controlling cellular processes. YAP1/TAZ activation drives oncogenesis, metastasis, and resistance to chemotherapy by promoting key cellular behaviors such as immune evasion and tumor cell survival.

Osteochondral tissue comprises two structurally and functionally distinct regions: An avascular, low-cellularity cartilage layer with poor self-healing capacity, and a vascularized, mineralized subchondral bone. This pronounced heterogeneity complicates the repair of defects that span both regions. Conventional clinical treatments, such as microfracture and autologous chondrocyte implantation, often fail to restore the native biphasic architecture, leading to disorganized fibrocartilage and poor tissue integration. Tissue engineering has emerged as a promising strategy by integrating mesenchymal stem cells (MSCs) with engineered biomaterial scaffolds. However, spatially directing MSCs toward chondrogenic and osteogenic lineages remains challenging. Beyond biochemical cues, biophysical cues play pivotal roles in modulating MSC fate via integrin-mediated mechanotransduction, cytoskeletal remodeling, and mechanosignaling pathways, including TRPV4, Piezo1, and YAP/TAZ. When appropriately encoded within scaffolds, these biophysical cues provide sustained, spatially defined guidance to MSCs. This review summarizes recent advances in scaffold design that leverage mechanobiology to construct biomimetic microenvironments, thereby manipulating lineage-specific MSC differentiation and facilitating layered, stratified osteochondral regeneration.

Rheumatoid arthritis (RA) is a chronic autoimmune disorder that is pathologically defined by persistent synovitis and systemic inflammation. Currently, the clinical diagnosis and management of RA remain challenging, particularly with respect to early detection, the treatment of refractory cases, and ensuring long-term medication safety. Therefore, it is imperative to deepen our understanding of RA pathogenesis, identify specific biomarkers, and develop innovative therapeutic strategies. This review summarizes the roles and recent advances concerning extracellular vesicles (EVs) in RA progression, diagnosis, and therapeutic development. Research indicates that during RA development, joint-resident cells, immune cells, and relevant body fluids form a complex network in which EV-mediated signaling amplifies inflammatory responses and exacerbates tissue damage. Moreover, studies have shown that EVs isolated from synovial fluid and the circulation of RA patients exhibit significantly altered expression profiles, morphology, or subtype composition. These alterations are closely associated with disease activity, underscoring their potential as diagnostic biomarkers and tools for monitoring disease severity. Regarding therapy, EVs derived from diverse cellular sources have demonstrated promising therapeutic potential in RA. They not only carry bioactive molecules that can modulate RA-associated cells, but also serve as engineered delivery vehicles for targeted therapeutic interventions. In summary, EVs play multifaceted roles in the progression, diagnosis, and treatment of RA. Future research should focus on translating EV-related discoveries into clinical applications, thereby supporting the development of novel strategies for the precise diagnosis and management of RA.

The process of wound healing is intricate and, once disrupted, results in scar formation. Scar formation has negative physiological and psychological impacts on patients in addition to impeding the restoration of skin integrity and function. Increasing evidence indicates that factors such as angiogenesis, ECM deposition, and inflammation are all associated with scar formation. Given their excellent immunomodulatory and regenerative properties, mesenchymal stem cell-derived exosomes (MSCs-Exos) are increasingly favored in inhibiting scar formation during wound healing. This review begins with a summary of the key mechanisms of wound healing and scar formation, followed by the application of MSCs-Exos in attenuating the pathological process of scar formation, as well as its potential mechanisms of action. In addition, the current status and development prospects of engineered exosomes and hydrogel-combined exosomes in scar inhibition are further discussed. Finally, we evaluate the current challenges of using exosomes for scarless wound healing, including manufacturing standardization, dosing, delivery systems, and the lack of large-scale clinical data, which hold the potential to bridge the gap between the laboratory and the clinical.

Chronic kidney disease (CKD) and renal fibrosis remain major global health burdens, with limited options for early diagnosis and effective therapy. Conventional approaches, such as kidney biopsy and imaging, are invasive or insensitive to early-stage changes. Microfluidic technology has emerged as a transformative platform that enables precise modeling of renal microenvironments, sensitive biomarker detection, and physiologically relevant drug testing. This review evaluates recent advances in microfluidics for CKD and fibrosis, with emphasis on mechanistic insights, diagnostic innovations, and therapeutic strategies.

Cell-based therapy is a promising approach for ischemic stroke treatment. This systematic review and meta-analysis aimed to consolidate clinical evidence on the use of neuroimaging to evaluate stem cell therapy across all stages of stroke recovery.