Most eukaryotic cells secrete extracellular vesicles called exosomes, which are involved in intercellular communication. Exosomes play a role in tumor development and metastasis by transporting bioactive chemicals from cancerous cells to other cells in local and distant microenvironments. However, the potential of exosomes can be used by engineering them and considering different therapeutic approaches to overcome tumors. Exosomes are a promising drug delivery approach that can help decrease side effects from traditional treatments like radiation and chemotherapy by acting as targeted agents at the tumor site. The present review provides an overview of exosomes and various aspects of the role of exosomes in cancer development, which include these items: exosomes in cancer diagnosis, exosomes and drug delivery, exosomes and drug resistance, exosomal microRNAs and exosomes in tumor microenvironment, etc. Cancer stem cells release exosomes that nurture tumors, promoting unwanted growth and regeneration, and these types of exosomes should be inhibited. Ironically, exosomes from other cells, such as hepatocytes or mesenchymal stem cells (MSCs), are vital for healing organs like the liver and repairing gastric ulcers. Without proper treatment, this healing process can backfire, potentially leading to disease progression or even cancer. What can be found from various studies about the role of exosomes in the field of cancer is that exosomes act like a double-edged sword; on the other hand, natural exosomes in the body may play an important role in the process and progression of cancer, but by engineering exosomes, they can be directed towards target therapy and targeted delivery of drugs to tumor cells. By examining the role and application of exosomes in various mechanisms of cancer, it is possible to help treat this disease more efficiently and quickly in preclinical and clinical research.

Extracellular vesicles (EVs) are widely explored as vehicles for delivering therapeutic or experimental cargo to cardiomyocytes. Efforts to improve EV bioavailability in the heart, and reduce their off-target actions, require screening methods that can replicate the physiological and anatomical barriers present in the myocardium. Additionally, discovery pipelines must exercise control over EV dosage and timing, and provide a means of assessing cargo incorporation into cardiomyocytes specifically. These criteria are not generally met by experiments on cultured cells or animals. Here, we present a Langendorff-heart discovery pipeline that combines the strengths of in vivo and in vitro approaches. Langendorff-mode perfusion enables controlled exposure of beating hearts to re-circulated EVs. Following perfusion, cardiomyocytes can be isolated enzymatically for analysis, such as imaging. We tested this discovery pipeline by functionalizing EVs with beta-blockers (atenolol, metoprolol) using click-chemistry and incorporating the fluorescent protein NeonGreen2 to track the fate of EV cargo. Fluorescence in cardiomyocytes, including their nuclear regions, increased after Langendorff-treatment with beta-blocker decorated EVs, but only if these contained NeonGreen2, implicating the fluorescent cargo as the source of signal. Superior binding efficacy of beta-blockers was confirmed by referencing to the substantially lower signals obtained using wild-type EVs or EVs presenting myomaker or myomixer proteins, motifs that modestly enrich cardiac EV uptake in mice. Our findings demonstrate successful cardiomyocyte targeting using EVs decorated with beta-receptor binders. We propose the Langendorff-perfused heart as an intermediate step, nested between in vitro characterisation and animal testing, in discovery pipelines for seeking improved EV designs for the heart.

Acute kidney injury (AKI) has a high morbidity and mortality rate but can only be treated with supportive therapy in most cases. The diagnosis of AKI is mainly based on serum creatinine level and urine volume, which cannot detect kidney injury sensitive and timely. Therefore, new diagnostic and therapeutic molecules of AKI are being actively explored. Extracellular vesicles (EVs), secreted by almost all cells, can originate from different parts of the kidney and mediate intercellular communication between various cell types of nephrons. At present, numerous successful EV-based biomarker discoveries and treatments for AKI have been made, such as the confirmed diagnostic role of urine-derived EVs in AKI and the established therapeutic role of mesenchymal stem cell-derived EVs in AKI have been confirmed; however, these related studies lack a full discussion. In this review, we summarize the latest progression in the profound understanding of the functional role of EVs in AKI caused by various etiologies in recent years and provide new insights into EVs as viable biomarkers and therapeutic molecules for AKI patients. Furthermore, the current challenges and prospects of this research area are briefly discussed, presenting a comprehensive overview of the growing foregrounds of EVs in AKI.

Lung cancer poses a significant global burden with rising morbidity and mortality. Coal tar pitch-induced lung cancer is an occupational disease where early detection is crucial but challenging due to unclear pathogenesis. We established a malignant transformation model using BEAS-2B cells treated with coal tar pitch extract (CTPE). Macro- and micro-observations showed CTPE-induced alterations, including changes in cell morphology, enhanced proliferation and migration abilities, upregulated EGFR expression, modified levels of CYP1A1 and GSTM1 metabolizing enzymes, and a transition towards a mesenchymal phenotype. These findings strongly suggest that the cells have undergone malignant transformation. Metabolomics analysis revealed changes in 1120 metabolites, with 31 co-expressed, mainly in energy and amino acid metabolism. Small extracellular vesicles (SEVs) concentrations and EGFR levels were significantly altered. Correlation analysis identified a relationship between these biomarkers, implying their potential significance as early events in the initiation and progression of lung cancer. These findings provide valuable insights and a rationale for lung cancer screening and mechanistic investigations, thereby contributing to a deeper understanding of the disease.

Extracellular vesicles (EVs), which are secreted by various cell types, hold significant potential for cancer therapy. However, there are several challenges and difficulties that limit their application in clinical settings. This review, which integrates the work of our team and recent advancements in this research field, discusses EV-based cancer treatment strategies to guide their clinical application. The following treatment strategies are discussed: 1) leveraging the inherent properties of EVs for the development of cancer treatments; 2) modifying EVs using EV engineering methods to improve drug loading and delivery; 3) targeting key molecules in tumor-derived EV (TDE) synthesis to inhibit their production; and 4) clearing TDEs from the tumor microenvironment. Additionally, on the basis of research into EV-based vaccines and bispecific antibodies, this review elaborates on strategies to enhance antitumor immunity via EVs and discusses engineering modifications that can improve EV targeting ability and stability and the research progress of AI technology in targeted delivery of EV drugs. Although there are limited strategies for enhancing EV targeting abilities, this review provides an in-depth discussion of prior studies. Finally, this review summarizes the clinical progress on the use of EVs in cancer therapy and highlights challenges that need to be addressed.

Stroke is a challenging neurological condition caused by interrupted blood flow to the brain and presents substantial global health concerns due to its prevalence and limited treatment options. Exosomes, tiny vesicles released by cells, are gaining attention for their potential in targeted drug delivery and as diagnostic and therapeutic biomarkers for stroke. This article outlines recent advances in exosome-based drug delivery systems and examines their application in managing stroke. Stroke presents with diverse symptoms depending on the brain region affected, and current treatments primarily aim to restore blood flow and manage risk factors. Exosomes exhibit a unique structure and composition and contain bioactive molecules. Their ability to cross the blood-brain barrier and target specific cells makes them promising candidates for precise drug delivery in stroke therapy. Exosomes contribute extensively to stroke pathophysiology and present considerable therapeutic promise by promoting neuroprotection and assisting in brain repair mechanisms. They can be engineered to carry various therapeutic substances, such as small molecules, enabling highly specific targeted delivery. Furthermore, the molecular compositions of exosomes reflect the pathological changes observed in stroke, indicating their potential use as biomarkers for early diagnosis, monitoring of disease progression, and creating individualized treatment strategies. Despite promising developments, challenges remain in optimizing exosome production, purification, and cargo loading. Further investigations into their biological mechanisms and clinical validation are crucial for translating their potential into tangible benefits for patients. This article highlights recent advances and future prospects in exosome research, underscoring their application as novel diagnostic and therapeutic tools in stroke management.

Exosomes are nanoscale extracellular vesicles released by diverse cell types, serving essential functions in intercellular communication and physiological processes. These vesicles have garnered considerable interest in recent years for their potential as drug delivery systems, attributed to their natural origin, minimal immunogenicity, high biocompatibility, and capacity to traverse biological barriers, including the blood-brain barrier. Exosomes can be obtained from diverse biological fluids, rendering them accessible and versatile vehicles for therapeutic medicines. This study emphasizes the burgeoning significance of exosomes in drug administration, concentrating on their benefits, including improved stability, target selectivity, and the capacity to encapsulate various biomolecules, such as proteins, nucleic acids, and small molecules. Notwithstanding their potential applications, other problems remain, including as effective drug loading, industrial scalability, and the standardization of isolation methodologies. Overcoming these hurdles via new research is essential for fully harnessing the promise of exosomes in therapeutic applications, especially in the treatment of intricate diseases like cancer and neurological disorders.

Alzheimer's disease and other neurodegenerative disorders are characterized by the accumulation of misfolded proteins, such as amyloid-beta, tau, and α-synuclein, which disrupt neuronal function and contribute to cognitive decline. Heparan sulfate proteoglycans, particularly syndecans, play a pivotal role in the seeding, aggregation, and spreading of toxic protein aggregates through endocytic pathways. Among these, syndecan-3 is particularly critical in regulating the internalization of misfolded proteins, facilitating their propagation in a prion-like manner. This review examines the mechanisms by which syndecans, especially SDC3, contribute to the seeding and spreading of pathological protein aggregates in neurodegenerative diseases. Understanding these endocytic pathways provides valuable insights into the potential of syndecans as biomarkers and therapeutic targets for early intervention in Alzheimer's disease and other related neurodegenerative disorders.

Vaccine formulations are a successful strategy against pathogen transmission because vaccine candidates induce effective and long-lasting memory immune responses (B and CD4+ T cells) at systemic and mucosal sites. Extracellular vesicles of lipoproteins, bioactive compounds from plants and invertebrates (sponges) encapsulated in liposomes, and glycoproteins can target these sites. The vaccine candidates developed can mimic microbial pathogens in a way that successfully links the innate and adaptive immune responses. In addition, vaccines plus adjuvants promote and maintain an inflammatory response. In this review, we aimed to identify the host-pathogen interface as a rich source of candidate targets for vaccine-induced protective and long-lasting memory immune responses.

Exosomes are microscopic vesicles released by cells that transport various biological materials and play a vital role in intercellular communication. When they are engineered, they serve as efficient delivery systems for therapeutic agents, making it possible to precisely deliver active pharmaceutical ingredients to organs, tissues, and cells. Exosomes' pharmacokinetics, or how they are transported and metabolized inside the body, is affected by several factors, including their source of origination and the proteins in their cell membranes. The pharmacokinetics and mobility of both native and modified exosomes are being observed in living organisms using advanced imaging modalities such as in vitro-in vivo simulation, magnetic resonance imaging, and positron emission tomography. Establishing comprehensive criteria for the investigation of exosomal pharmacokinetic is essential, given its increasing significance in both therapy and diagnostics. To obtain a thorough understanding of exosome intake, distribution, metabolism, and excretion, molecular imaging methods are crucial. The development of industrial processes and therapeutic applications depends on the precise measurement of exosome concentration in biological samples. To ensure a seamless incorporation of exosomes into clinical practice, as their role in therapeutics grows, it is imperative to conduct a complete assessment of their pharmacokinetics. This review provides a brief on how exosome-based research is evolving and the need for pharmacokinetic consideration to realize the full potential of these promising new therapeutic approaches.

Photothermal and photodynamic therapies represent effective modalities for combatting bacteria and tumor cells. However, therapeutic outcomes are constrained by limitations related to the heat and reactive oxygen species (ROS) transfer distance from photosensitizers to targets. To address this issue, we have devised and developed exosome-decorated bio-heterojunctions (E-bioHJ) consisted of MXene (Ti3C2), liquid metal (LM) and exosomes sourced from CT26 cells to enhance the phototherapeutic consequences. Engineering E-bioHJ enhances phototherapeutic effect in antibacterial and anti-tumor treatment, which is ascribed to reducing transfer distance of the heat and ROS. When adorned with exosomes, E-bioHJ is targetedly delivered into the cytoplasm of tumor cells to generate amount heat and ROS under 808 nm near-infrared radiation, which further induces mitochondrial dysfunction and apoptosis/necroptosis. As envisaged, this study presents a novel tactic to enhance the antibacterial and anti-tumor efficacy of biomaterials through reducing the heat and ROS delivery travel distance.

Premature ovarian insufficiency (POI) presents a multifaceted challenge with limited treatment options. This study explored the therapeutic potential of exosome-based interventions for chemotherapy-induced POI.

Adapted exosomes were engineered from umbilical cord mesenchymal stem cells (UC-MSCs) under a specific co-culture system and used for treating in vitro and in vivo models of chemotherapy-induced premature ovarian insufficiency.

In vitro models revealed the significant impact of adapted exosomes, which promoted granulosa cell proliferation, decrease apoptosis, and enhanced ovarian functional markers. The findings in an in vivo chemotherapy-induced POI mouse model indicated the restoration of ovarian morphology, follicle numbers, and fertility in both the naïve and adapted exosome-treated groups. Notably, the adapted exosome group demonstrated a heightened pregnancy rate, increased numbers of primary follicles, and a significant reduction in ovarian apoptosis. MiRNA profiling revealed distinctive cargo in the adapted exosomes, among which miR-20b-5p played a pivotal role in regulating apoptosis and inflammation; this finding is especially important given that apoptosis is one of the primary complications of chemotherapy-induced POI. Furthermore, cells treated with adapted exosomes demonstrated significant overexpression of miR-20b-5p, resulting in decreased PTEN expression and the activation of the PI3K-AKT pathway-a crucial mechanism in mitigating chemotherapy-induced POI.

This study introduces an exosome-based therapeutic approach, emphasizing the importance of exosome cargo composition in treating disorders. Further investigation into the identified miRNA profile in adapted exosomes is necessary to clarify the underlying mechanisms, potentially leading to the development of a new treatment for clinical premature ovarian insufficiency.

Exosomes are small extracellular vesicles naturally secreted by cells into body fluids, enriched with bioactive molecules such as RNAs, proteins, and lipids. These nanosized vesicles play a crucial role in physiological and pathological processes by facilitating intercellular communication and modulating cellular responses, particularly within the central nervous system (CNS). Their ability to cross the blood-brain barrier and reflect the characteristics of their parent cells makes exosomal cargo a promising candidate for biomarkers in the early diagnosis and clinical assessment of neurological conditions. This review offers a comprehensive overview of current knowledge on the characterization of mammalian-derived exosomes, their application as drug delivery systems for neurological disorders, and ongoing clinical trials involving exosome-loaded cargo. Despite their promising attributes, a significant challenge remains the lack of standardized isolation methods, as current techniques are often complex, costly, and require sophisticated equipment, affecting the scalability and affordability of exosome-based therapies. The review highlights the engineering potential of exosomes, emphasizing their ability to be customized for targeted therapeutic delivery through surface modification or conjugation. Future advancements in addressing these challenges and leveraging the unique properties of exosomes could lead to innovative and effective therapeutic strategies in neurology.

Exosomes are indispensable extracellular vesicles that facilitate intercellular communication and are crucial for both healthy and pathological conditions, including cancer. The capacity of exosomes to echo the molecular characteristics of their cells of origin, including malignant cells, makes them indispensable tools for diagnosing and tracking disease progression in the field of oncology. Oral squamous cell carcinoma (OSCC), which has been identified as the sixth most prevalent cancer worldwide, has been linked to numerous risk factors, including tobacco use, alcohol consumption, human papillomavirus (HPV) infection, and inadequate oral hygiene. Exosomes pointedly influence the advancement of oral cancer via promoting tumor cell growth, invasion, angiogenesis, and immune evasion through the alteration of the tumor microenvironment. A critical apparatus in cancer metastasis is the epithelial-to-mesenchymal transition (EMT), during which cancer cells acquire improved migratory and invasive properties. EMT plays a role in metastasis, resistance to treatment, and evasion of the immune response. Exosomes facilitate EMT in oral cancer by delivering bioactive molecules that influence EMT signaling pathways. These exosomes inspire EMT in recipient cells, by this means enhancing tumor invasion and metastasis. This study aims to identify the specific exosomal components and signaling pathways that are tangled in EMT, in that way providing new avenues for targeted therapies designed to hinder the metastasis of oral cancer.

Plant-derived exosome-like nanoparticles (PDENs), emerging as novel bioactive agents, exhibit significant potential in food science and nutritional health. These nanoparticles, enriched with plant-specific biomolecules such as proteins, lipids, nucleic acids, and secondary metabolites, demonstrate unique cross-species regulatory capabilities, enabling interactions with mammalian cells and gut microbiota. PDENs enhance nutrient bioavailability by protecting sensitive compounds during digestion, modulate metabolic pathways through miRNA-mediated gene regulation, and exhibit anti-inflammatory and antioxidant properties. For instance, grape-derived PDENs reduce plasma triglycerides in high-fat diets, while ginger-derived nanoparticles alleviate colitis by downregulating pro-inflammatory cytokines. Additionally, PDENs serve as natural drug carriers, with applications in delivering therapeutic agents like doxorubicin and paclitaxel. Despite these advancements, challenges remain in standardizing extraction methods (ultracentrifugation, immunoaffinity), ensuring stability during food processing and storage, and evaluating long-term safety. Current research highlights the need for optimizing lyophilization techniques and understanding interactions between PDENs and food matrices. Furthermore, while PDENs show promise in functional food development-such as fortified beverages and probiotic formulations-their clinical translation requires rigorous pharmacokinetic studies and regulatory clarity. This review synthesizes existing knowledge on PDENs' composition, biological activities, and applications, while identifying gaps in scalability, stability, and safety assessments. Future directions emphasize interdisciplinary collaboration to harness PDENs' potential in combating metabolic disorders, enhancing food functionality, and advancing personalized nutrition strategies.

The incidence and mortality rates of digestive tract tumors, especially gastric and colorectal cancers, are high worldwide. Owing to their unique advantages, such as efficient drug loading, safety, and targeting properties, nanoparticles (NPs) have demonstrated great potential in the treatment of gastrointestinal tumors. However, their practical application is limited by several factors, such as high costs, few clinical trials, and long approval periods. In this review, we summarize three types of immunotherapeutic nanomaterial drugs for gastrointestinal tumors: organic, inorganic, and hybrid nanomaterials. This article also discusses the current status of research and development in this field and the advantages of each type of material to provide theoretical references for developing new drugs and advancing clinical research.

Oxaliplatin (OXA) is the first-line drug for the treatment of colorectal cancer (CRC), and susceptibility to drug resistance affects patient prognosis. However, the exact underlying mechanisms remain unclear. Platinum-acquired resistance in CRC is a continuous transition process; though, current research has mainly focused on the end state of drug resistance, and the early events of drug resistance have been ignored. In this study, single-cell transcriptome sequencing is combined with a dynamic network biomarker (DNB), and found that the functional inhibition of the mitochondrial electron transport chain complex I occur early in the development of attained resistance to OXA in CRC cells, as evidenced by a decrease in the levels of subunit proteins, primarily NDUFB8. Specifically, the mouse double minute 2 homologue (MDM2) mediates the ubiquitination and degradation of NDUFB8, reducing intracellular reactive oxygen species (ROS) generation under chemotherapeutic stress, consequently contributing to drug resistance. Based on this, the study constructs engineered extracellular vesicles carrying siMDM2 by electroporation and validates the application of EV-siMDM2 to improve the efficacy of OXA-based chemotherapy by inhibiting the MDM2/NDUFB8/ROS signaling axis in patient-derived xenograft (PDX) and hepatic and pulmonary metastasis mouse models, thus providing new ideas and an experimental basis for the platinum-resistant treatment of CRC.

Exosomes have emerged as promising tools for targeted drug delivery in biomedical applications and medicine. This review delves into the scientific advancements, challenges, and future prospects specifically associated with these technologies. In this work, we trace the research milestones that led to the discovery and characterization of exosomes and extracellular vesicles, and discuss strategies for optimizing the synthetic yield and the loading of these particles with various therapeutics. In addition, we report the current major issues affecting the field and hampering the clinical translation of these technologies. Highlighting the pivotal role of imaging techniques, we explore how they drive exosome therapy and development by offering insights into biodistribution and cellular trafficking dynamics. Methodologies for vesicle isolation, characterization, loading, and delivery mechanisms are thoroughly examined, alongside strategies aimed at enhancing their therapeutic efficacy. Special emphasis was dedicated to their therapeutic properties, particularly to their ability to deliver biologics into the cytoplasm. Furthermore, we delve into the intricate balance between surface modifications and targeting properties including also transgenic methods aimed at their functionalization and visualization within biological systems. This review underscores the transformative potential of these carriers in targeted drug delivery and identifies crucial areas for further research and clinical translation.

Bone marrow mesenchymal/stromal stem cell (BMSC)-derived small extracellular vesicles (sEVs) are promising therapeutic agents owing to their low immunogenicity and ability to cross biological barriers. Doxorubicin (DOX), a common chemotherapeutic agent, damages testicular tissue. This study aimed to enhance the antioxidant activity of sEVs by activating the Nrf2 gene in BMSCs and evaluate their therapeutic potential for DOX-induced fertility disorders. Testicular damage was induced by DOX in NMRI mice. BMSCs from Wistar rats were treated with Bardoxolone methyl (BaMet) to upregulate Nrf2. The sEVs were isolated through differential ultracentrifugation and validated for size, morphology, and protein expression. The antioxidant activity was assessed using specific kits. sEVs containing 10 μg of proteins were injected intravenously into DOX-injured mice. After 35 days, the testes were collected for histopathological, hormonal, and immunological analyses, along with the evaluation of sperm parameters. Male and female mice were paired to determine the pregnancy rates. BaMet-sEVs exhibited higher antioxidant activity and significantly improved serum testosterone levels, testicular cell populations, sperm viability, and motility in DOX-injured mice. In addition, BaMet-sEVs treatment enhanced fertility and increased the number of offspring. This study demonstrated the effectiveness of BaMet-sEVs in mitigating DOX-induced testicular damage.

Colorectal cancer (CRC) represents a common type of carcinoma with significant mortality rates globally. A primary factor contributing to the unfavorable treatment outcomes and reduced survival rates in CRC patients is the occurrence of metastasis. Various intricate molecular mechanisms are implicated in the metastatic process, leading to mortality among individuals with CRC. In the realm of intercellular communication, exosomes, which are a form of extracellular vesicle (EV), play an essential role. These vesicles act as conduits for information exchange between cells and originate from multiple sources. By fostering a microenvironment conducive to CRC progression, exosomes and EVs significantly influence the advancement of the disease. They contain a diverse array of molecules, including messenger RNAs (mRNAs), non-coding RNAs (ncRNAs), proteins, lipids, and transcription factors. Notably, ncRNAs, such as microRNAs (miRNAs), long non-coding RNAs (lncRNAs), and circular RNAs (circRNAs), are prominently featured within exosomes. These ncRNAs have the capacity to regulate various critical molecules or signaling pathways, particularly those associated with tumor metastasis, thereby playing a crucial role in tumorigenesis. Their presence indicates a substantial potential to affect vital aspects of tumor progression, including proliferation, metastasis, and resistance to treatment. This research aims to categorize exosomal ncRNAs and examine their functions in colorectal cancer. Furthermore, it investigates the clinical applicability of novel biomarkers and therapeutic strategies in CRC. Abbreviations: ncRNAs, non-coding RNAs; CRC, Colorectal cancer; EV, extracellular vesicle; mRNAs, messenger RNAs; miRNAs, microRNAs; lncRNAs, long non-coding RNAs; circRNAs, circular RNAs; HOTTIP, HOXA transcript at the distal tip; NSCLC, non-small cell lung cancer; 5-FU, 5-fluorouracil; OX, Oxaliplatin; PDCD4, programmed cell death factor 4; Tregs, regulatory T cells; EMT, epithelial-mesenchymal transition; PFKFB3, 6-phosphofructo-2-kinase/fructose-2,6-biphosphatase 3; USP2, ubiquitin carboxyl-terminal hydrolase 2; TNM, tumor node metastasis; TAMs, tumor-associated macrophages; RASA1, RAS p21 protein activator 1; PDCD4, programmed cell death 4; ZBTB2, zinc finger and BTB domain containing 2; SOCS1, suppressor of cytokine signaling 1; TUBB3, β-III tubulin; MSCs, mesenchymal stem cells.

The oral and maxillofacial region is a highly complex area composed of multiple tissue types and bears various critical functions of the human body. Diseases in this region pose significant diagnostic and management challenges; therefore, exploring new strategies for early diagnosis, targeted treatment, and tissue reconstruction is key to improving patient prognosis and quality of life. Extracellular vesicles are a group of heterogeneous lipid-bilayer membrane structures secreted by most cell types, including exosomes, microvesicles, and apoptotic bodies. Present in various body fluids and tissues, they act as messengers via the transfer of nucleic acids, proteins, and metabolites to recipient cells. To date, studies have revealed the different roles of extracellular vesicles in physiological or pathological processes, as well as applications in disease diagnosis, prognosis, and treatment. The importance and tissue specificity of the dental and maxillofacial tissues indicate that extracellular vesicles derived from this region are promising for further research. This paper reviews the published data on extracellular vesicles derived from cells, body fluids, and tissues in oral and maxillofacial regions, summarizes the latest advances in extracellular vesicles from extensive sources, and concludes with a focus on the current research progress and application prospects of engineered exosomes in oral science.

Alzheimer's disease (AD) represents an escalating global health crisis, constituting the leading cause of dementia among the elderly and profoundly impairing their quality of life. Current FDA-approved drugs, such as rivastigmine, donepezil, galantamine, and memantine, offer only modest symptomatic relief and are frequently associated with significant adverse effects. Faced with this challenge and in line with advances in the understanding of the pathophysiology of this neurodegenerative condition, various innovative therapeutic strategies have been explored. Here, we review novel approaches inspired by advanced knowledge of the underlying pathophysiological mechanisms of the disease. Among the therapeutic alternatives, immunotherapy stands out, employing monoclonal antibodies to specifically target and eliminate toxic proteins implicated in AD. Additionally, the use of medicinal plants is examined, as their synergistic effects among components may confer neuroprotective properties. The modulation of the gut microbiota is also addressed as a peripheral strategy that could influence neuroinflammatory and degenerative processes in the brain. Furthermore, the therapeutic potential of emerging approaches, such as the use of microRNAs to regulate key cellular processes and nanotherapy, which enables precise drug delivery to the central nervous system, is analyzed. Despite promising advances in these strategies, the incidence of Alzheimer's disease continues to rise. Therefore, it is proposed that achieving effective treatment in the future may require the integration of combined approaches, maximizing the synergistic effects of different therapeutic interventions.

Exosomes (Exos) from adipose derived stem cells (ADSCs) can delay skin photoaging, but their effects on reactive oxygen species (ROS) remains unclear. This study aimed to investigate the relationship between adipose derived stem cell exosomes (ADSCs-Exos) in anti-photoaging of skin and glutathione (GSH)/ ROS expression in human fibroblasts.

A skin photoaging model was established by irradiating human fibroblasts with ultraviolet B (UVB) light in vitro. Next, exosomes from ADSCs were isolated for treating the photoaged fibroblasts. Afterwards, the alterations in photoaged fibroblasts were analyzed by a series of assays including senescence-associated β-galactosidase (SA-β-Gal) staining, p16 expression, ROS staining, and GSH content.

After a human fibroblast photoaging model was subjected to ADSCs-Exos treatment, we found that the high concentration exosome group had the highest GSH content. Cellular staining showed that levels of SA-β-Gal, p16, and ROS of the high concentration-treated group were lower than other groups.

ADSCs-Exos can protect skin fibroblasts from photoaging via increasing the ratio of GSH/ROS.

Lung diseases account for over four million premature deaths every year, and experts predict that this number will increase in the future. The top cause of death globally is diseases which include conditions like lung cancer asthma and COPD. Treating severe acute lung injury is a complex task because lungs struggle to heal themselves in the presence of swelling inflammation and scarring caused by damage, to the lung tissues. Though achieving lung regeneration, in controlled environments is still an ambition; ongoing studies are concentrating on notable progress, in the field of lung tissue engineering and methods for repairing lung damage. This review delves into methods, for regenerating lungs with a focus on exosome carry bioscaffolds and mesenchymal stem cells among others. It talks about how these new techniques can help repair lung tissue and improve lung function in cases of damage. Also noted is the significance of ex vivo lung perfusion (EVLP), for rejuvenating donor lungs and the healing properties of exosomes in supporting lung regeneration.

Triple-negative breast cancer (TNBC) is an aggressive subtype of breast cancer that has no therapeutic targets, relies on chemotherapeutics for treatment, and is in dire need of novel therapeutic approaches for improved patient outcomes. Extracellular vesicles (EVs) serve as intercellular communicators and have been proposed as ideal drug delivery vehicles. Here, EVs were engineered with RNA nanotechnology to develop TNBC tumor inhibitors. Using super resolved-structured illumination microscopy, EVs were optimized for precise Survivin small interfering RNA (siRNA) conjugated to chemotherapeutics loading and CD44 aptamer ligand decoration, thereby enhancing specificity toward TNBC cells. Conventional treatments typically employ chemotherapy drugs gemcitabine (GEM) and paclitaxel (PTX) at dosages on the order of mg/kg respectively, per injection (intravenous) in mice. In contrast, engineered EVs encapsulating these drugs saw functional tumor growth inhibition at significantly reduced concentrations: 2.2 μg/kg for GEM or 5.6 μg/kg for PTX, in combination with 21.5 μg/kg survivin-siRNA in mice. The result is a substantial decrease in the chemotherapeutic dose required, by orders of magnitude, compared with standard regimens. In vivo and in vitro evaluations in a TNBC orthotopic xenograft mouse model demonstrated the efficacy of this decreased dosage strategy, indicating the potential for decreased chemotherapy-associated toxicity.

High efficacy, selectivity and cellular targeting of therapeutic agents has been an active area of investigation for decades. Currently, most clinically approved therapeutics are small molecules or protein/antibody biologics. Targeted action of small molecule drugs remains a challenge in medicine. In addition, many diseases are considered 'undruggable' using standard biomacromolecules. Many of these challenges however, can be addressed using nucleic therapeutics. Nucleic acid drugs (NADs) are a new generation of gene-editing modalities characterized by their high efficiency and rapid development, which have become an active research topic in new drug development field. However, many factors, including their low stability, short half-life, high immunogenicity, tissue targeting, cellular uptake, and endosomal escape, hamper the delivery and clinical application of NADs. Scientists have used chemical modification techniques to improve the physicochemical properties of NADs. In contrast, modified NADs typically require carriers to enter target cells and reach specific intracellular locations. Multiple delivery approaches have been developed to effectively improve intracellular delivery and the in vivo bioavailability of NADs. Several NADs have entered the clinical trial recently, and some have been approved for therapeutic use in different fields. This review summarizes NADs development and evolution and introduces NADs classifications and general delivery strategies, highlighting their success in clinical applications. Additionally, this review discusses the limitations and potential future applications of NADs as gene therapy candidates.

Dry eye is characterized by persistent instability and decreased tear production, which are accompanied by epithelial lesions and inflammation on the surface of the eye. In our previous paper, we reported that supplementation with Limosilactobacillus fermentum HY7302 (HY7302) could inhibit corneal damage in a benzalkonium chloride (BAC)-induced mouse model of dry eye, through its effects in gut microbiome regulation. The aim of this study was to determine what functional extracellular substances can alter the inflammatory response of conjunctival cells. We isolated exosomes from HY7302 probiotic culture supernatant, analyzed their morphological characteristics, and found that their average size was 143.8 ± 1.1 nm, which was smaller than the exosomes from the L. fermentum KCTC 3112 strain. In addition, HY7302-derived exosomes significantly reduced the levels of genes encoding pro-inflammatory cytokines, including interleukin (IL)-20, IL-8, IL-6, and IL-1B, in BAC-treated human conjunctival cells. Moreover, HY7302-derived exosomes significantly increased the levels of genes encoding tight junction proteins, including TJP1, TJP2, and occludin-1, in Caco-2 cells. Lastly, the HY7302 exosomes reduced mRNA expression levels of IL1B, IL20, IL6, IL8, and NFAT5 in a transwell coculture system. Our findings indicate that HY7302 exosomes have potential for use in the treatment of ocular inflammation-related dry eye disease, through gut-eye axis communication via exosomes.

Milk-derived extracellular vesicles (mEVs) are emerging as promising therapeutic candidates due to their unique properties and versatile functions. These vesicles play a crucial role in immunomodulation by influencing macrophage differentiation and cytokine production, potentially aiding in the treatment of conditions such as bone loss, fibrosis, and cancer. mEVs also have the capacity to modulate gut microbiota composition, which may alleviate the symptoms of inflammatory bowel diseases and promote intestinal barrier integrity. Their potential as drug delivery vehicles is significant, enhancing the stability, solubility, and bioavailability of anticancer agents while supporting wound healing and reducing inflammation. Additionally, bovine mEVs exhibit anti-aging properties and protect skin cells from UV damage. As vaccine platforms, mEVs offer advantages including biocompatibility, antigen protection, and the ability to elicit robust immune responses through targeted delivery to specific immune cells. Despite these promising applications, challenges persist, including their complex roles in cancer, effective antigen loading, regulatory hurdles, and the need for standardized production methods. Achieving high targeting specificity and understanding the long-term effects of mEV-based therapies are essential for clinical translation. Ongoing research aims to optimize mEV production methods, enhance targeting capabilities, and conduct rigorous preclinical and clinical studies. By addressing these challenges, mEVs hold the potential to revolutionize vaccine development and targeted drug delivery, ultimately improving therapeutic outcomes across various medical fields.

Microglia, the resident immune cells of the central nervous system (CNS), play a crucial role in maintaining neural homeostasis but can also contribute to disease and injury when this state is disrupted or conversely play a pivotal role in neurorepair. One way that microglia exert their effects is through the secretion of small vesicles, microglia-derived exosomes (MGEVs). Exosomes facilitate intercellular communication through transported cargoes of proteins, lipids, RNA, and other bioactive molecules that can alter the behavior of the cells that internalize them. Under normal physiological conditions, MGEVs are essential to homeostasis, whereas the dysregulation of their production and/or alterations in their cargoes have been implicated in the pathogenesis of numerous neurodegenerative diseases, including Alzheimer's disease (AD), Parkinson's disease (PD), multiple sclerosis (MS), spinal cord injury (SCI), and traumatic brain injury (TBI). In contrast, MGEVs may also offer therapeutic potential by reversing inflammation or being amenable to engineering for the delivery of beneficial biologics or drugs. The effects of MGEVs are determined by the phenotypic state of the parent microglia. Exosomes from anti-inflammatory or pro-regenerative microglia support neurorepair and cell survival by delivering neurotrophic factors, anti-inflammatory mediators, and molecular chaperones. Further, MGEVs can also deliver components like mitochondrial DNA (mtDNA) and proteins to damaged neurons to enhance cellular metabolism and resilience. MGEVs derived from pro-inflammatory microglia can have detrimental effects on neural health. Their cargo often contains pro-inflammatory cytokines, molecules involved in oxidative stress, and neurotoxic proteins, which can exacerbate neuroinflammation, contribute to neuronal damage, and impair synaptic function, hindering neurorepair processes. The role of MGEVs in neurodegeneration and injury-whether beneficial or harmful-largely depends on how they modulate inflammation through the pro- and anti-inflammatory factors in their cargo, including cytokines and microRNAs. In addition, through the propagation of pathological proteins, such as amyloid-beta and alpha-synuclein, MGEVs can also contribute to disease progression in disorders such as AD and PD, or by the transfer of apoptotic or necrotic factors, they can induce neuron toxicity or trigger glial scarring during neurological injury. In this review, we have provided a comprehensive and up-to-date understanding of the molecular mechanisms underlying the multifaceted role of MGEVs in neurological injury and disease. In particular, the role that specific exosome cargoes play in various pathological conditions, either in disease progression or recovery, will be discussed. The therapeutic potential of MGEVs has been highlighted including potential engineering methodologies that have been employed to alter their cargoes or cell-selective targeting. Understanding the factors that influence the balance between beneficial and detrimental exosome signaling in the CNS is crucial for developing new therapeutic strategies for neurodegenerative diseases and neurotrauma.

Exosomes, nano-sized extracellular vesicles, have emerged as a promising tool for the diagnosis and treatment of various intractable diseases, including chronic wounds and cancers. As our understanding of exosomes continues to grow, their potential as a powerful therapeutic modality in medicine is also expanding. This systematic review aims to examine the progress of exosome-based clinical trials and provide a comprehensive overview of the therapeutic perspectives of exosomes.

This systematic review strictly follows PRISMA guidelines and has been registered in PROSPERO, the International Prospective Register of Systematic Reviews. It encompasses articles from January 2000 to January 2023, sourced from bibliographic databases, with targeted search terms targeting exosome applications in clinical trials. During the screening process, strict inclusion and exclusion criteria were applied, including a focus on clinical trials utilizing different cell-derived exosomes for therapeutic purposes.

Among the 522 publications initially identified, only 10 studies met the stringent eligibility criteria after meticulous screening. The selection process involved systematically excluding duplicates and irrelevant articles to provide a transparent overview.

According to our systematic review, exosomes have promising applications in a variety of medical fields, including cell-free therapies and drug delivery systems for treating a variety of diseases, especially cancers and chronic wounds. To ensure safety, potency, and broader clinical applications, further optimization of exosome extraction, loading, targeting, and administration is necessary. While cell-based therapeutics are increasingly utilizing exosomes, this field is still in its infancy, and ongoing clinical trials will provide valuable insights into the clinical utility of exosomes.

Periodontitis is a significant independent risk factor for atherosclerosis. Yet, the exact mechanism of action is still not fully understood. In this study, we investigated the effect of exosomes-miR-155-5p derived from periodontal endothelial cells on atherosclerosis in vitro and in vivo. Higher expression of miR-155-5p was detected in the plasma exosomes of patients with chronic periodontitis (CP) and carotid atherosclerosis (CAS) compared to patients with CP. Also, the expression level of miR-155-5p was associated with the severity of CP. miR-155-5p-enriched exosomes from HUVECs increased the angiogenesis and permeability of HAECs and promoted the expression of angiogenesis, permeability, and inflammation genes. Along with the overexpression or inhibition of miR-155-5p, the biological effect of HUVECs-derived exosomes on HAECs changed correspondingly. In ApoE-/- mouse models, miR-155-5p-enriched exosomes promoted the occurrence of carotid atherosclerosis by increasing permeable and angiogenic activity. Collectively, these findings highlight a molecular mechanism of periodontitis in CAS, uncovering exosomal miR-155-5p derived periodontitis affecting carotid endothelial cells in an 'exosomecrine' manner. Exosomal miR-155-5p may be used as a biomarker and target for clinical intervention to control this intractable disease in future, and the graphic abstract was shown in Figure S1.

Gene mutation correction was challenging until the discovery of clustered regularly interspaced short palindromic repeats (CRISPR) and CRISPR-associated protein (Cas). CRISPR is a new era for genome modification, and this technology has bypassed the limitations of previous methods such as zinc-finger nuclease and transcription activator-like effector nuclease. Currently, this method is becoming the method of choice for gene-editing purposes, especially therapeutic gene editing in diseases such as cardiovascular, neurological, renal, genetic, optical, and stem cell, as well as blood disorders and muscular degeneration. However, finding the optimum delivery system capable of carrying this large complex persists as the main challenge of this technology. Therefore, it would be ideal if the delivery vehicle could direct the introduction of editing functions to specific cells in a multicellular organism. Exosomes are membrane-bound vesicles with high biocompatibility and low immunogenicity; they offer the best and most reliable way to fill the CRISPR/Cas9 system delivery gap. This review presents the current evidence on the molecular mechanisms and challenges of CRISPR/Cas9-mediated genome modification. Also, the role of CRISPR/Cas9 in the development of treatment and diagnosis of numerous disorders, from malignancies to viral infections, has been discussed. Lastly, the focus is on new advances in exosome-delivery technologies that may play a role in CRISPR/Cas9 delivery for future clinical settings.

Osteoarthritis (OA) is the most common type of arthritis characterized by progressive cartilage degradation, with its pathogenesis closely related to chondrocyte autophagy. Chondrocytes are the only cells in articular cartilage, and the function of chondrocytes plays a vital role in maintaining articular cartilage homeostasis. Autophagy, an intracellular degradation system that regulates energy metabolism in cells, plays an incredibly important role in OA. During the early stages of OA, autophagy is enhanced in chondrocytes, acting as an adaptive mechanism to protect them from various environmental changes. However, with the progress of OA, chondrocyte autophagy gradually decreases, leading to the accumulation of damaged organelles and macromolecules within the cell, prompting chondrocyte apoptosis. Numerous studies have shown that cartilage degradation is influenced by the senescence and apoptosis of chondrocytes, which are associated with reduced autophagy. The relationship between autophagy, senescence, and apoptosis is complex. While autophagy is generally believed to inhibit cellular senescence and apoptosis to promote cell survival, recent studies have shown that some proteins are degraded by selective autophagy, leading to the secretion of the senescence-associated secretory phenotype (SASP) or increased SA-β-Gal activity in senescent cells within the damaged region of human OA cartilage. Autophagy activation may lead to different outcomes depending on the timing, duration, or type of its activation. Thus, our study explored the complex relationship between chondrocyte autophagy and OA, as well as the related regulatory molecules and signaling pathways, providing new insights for the future development of safe and effective drugs targeting chondrocyte autophagy to improve OA.

The inexorable progression of neurodegenerative diseases (NDs), including Alzheimer's disease, Parkinson's disease, Huntington's disease, amyotrophic lateral sclerosis, and multiple sclerosis, is closely related to irreversible brain decline. Accurately characterizing pathophysiological features and identifying reliable biomarkers for early diagnosis and optimized treatment are critical. Hindered by the blood-brain barrier (BBB), obtaining sensitive monitoring indicators for disease progression and achieving efficient drug delivery remain significant challenges. Exosomes, endogenous nanoscale vesicles that carry key bioactive substances, reflect the intracellular environment and play an important role in cell signaling. They have shown promise in traversing the BBB, serving dual roles as potential biomarkers for NDs and vehicles for targeted drug delivery. However, the specific mechanisms by which exosome influence NDs are not fully understood, necessitating further investigation into their attributes and functionalities in the context of NDs. This review explores how exosomes mediate multifaceted interactions, particularly in exacerbating pathogenic processes such as oxidative stress, neuronal dysfunction, and apoptosis integral to NDs. It provides a comprehensive analysis of the profound impact of exosomes under stress and disease states, assessing their prospective utility as biomarkers and drug delivery vectors, offering new perspectives for tackling these challenging diseases.

Exosomes which are membrane vesicles released by cells have gained significant interest in the field of cancer therapy as a novel means of intercellular communication. Their role in immune activation and their pathophysiological functions in cancer therapy have been recognized. Exosomes carry diverse bioactive components including proteins, mRNA, microRNAs, and bioactive lipids. These molecules have therapeutic potential in promoting tissue regeneration, supporting stem cell activity, preventing cell death, modulating immune responses, and promoting the growth of new blood vessels. However, the precise roles of exosomes derived from mesenchymal stem cells (MSCs) in the treatment of various cancers are still not fully understood. Consequently, cancer stem cells (CSCs) can self-renew and differentiate into various cell types. Understanding the mechanisms that sustain their persistence is crucial for developing effective therapies. Exosomes have recently gained interest as vehicles for intercellular communication between CSCs and non-CSCs, influencing cancer progression and the microenvironment. Research is ongoing on the utilization of exosomes derived from cancer stem cells (CSC-Exosome) for cancer treatment. The composition of extracellular vesicles is influenced by the specific type and condition of the cells from which they are secreted. Circulating exosomes contain stable RNA molecules such as mRNAs, microRNAs, and long non-coding RNAs (lncRNAs). In this review, we will explore the significance of exosomes and their diverse cellular combinations in the context of cancer therapy.

Exosomes are regarded as having transformative potential for clinical applications. Exosome-based liquid biopsies offer a noninvasive method for early cancer detection and real-time disease monitoring. Clinical trials are underway to validate the efficacy of exosomal biomarkers for enhancing diagnostic accuracy and predicting treatment responses. Additionally, engineered exosomes are being developed as targeted drug delivery systems that can navigate the bloodstream to deliver therapeutic agents to tumor sites, thus enhancing treatment efficacy while minimizing systemic toxicity. Exosomes also exhibit immunomodulatory properties, which are being harnessed to boost antitumor immune responses. In this review, we detail the latest advances in clinical trials and research studies, underscoring the potential of exosomes to revolutionize cancer care.

Nano- and micro-sized vesicular and colloidal structures mediate cell-cell communication. They are important players in the physiology of plants, animals, and humans, and are a subject of increasing interest. We investigated the effect of three surfactants, N-cetylpyridinium chloride (CPC), sodium dodecyl sulfate (SDS), and Triton X-100 (TX100), and two anionic polyelectrolytes, sodium polystyrene sulfonate (NaPSS) and sodium polymethacrylate (NaPMA), on nanoliposomes. In addition, the effect of SDS and TX100 on selected biological membranes (erythrocytes and microalgae) was investigated. The liposomes were produced by extrusion and evaluated by microcalorimetry and light scattering, based on the total intensity of the scattered light (Itot), hydrodynamic radius (Rh), radius of gyration (Rg), shape parameter p (=Rh/Rg,0), and polydispersity index. The EPs shed from erythrocytes and microalgae Dunaliella tertiolecta and Phaeodactylum tricornutum were visualized by scanning electron microscopy (SEM) and analyzed by flow cytometry (FCM). The Rh and Itot values in POPC liposome suspensions with added CPC, SDS, and TX100 were roughly constant up to the respective critical micelle concentrations (CMCs) of the surfactants. At higher compound concentrations, Itot dropped towards zero, whereas Rh increased to values higher than in pure POPC suspensions (Rh ≈ 60-70 nm), indicating the disintegration of liposomes and formation of larger particles, i.e., various POPC-S aggregates. Nanoliposomes were stable upon the addition of NaPSS and NaPMA, as indicated by the constant Rh and Itot values. The interaction of CPC, SDS, or TX100 with liposomes was exothermic, while there were no measurable heat effects with NaPSS or NaPMA. The SDS and TX100 increased the number density of EPs several-fold in erythrocyte suspensions and up to 30-fold in the conditioned media of Dunaliella tertiolecta at the expense of the number density of cells, which decreased to less than 5% in erythrocytes and several-fold in Dunaliella tertiolecta. The SDS and TX100 did not affect the number density of the microalgae Phaeodactylum tricornutum, while the number density of EPs was lower in the conditioned media than in the control, but increased several-fold in a concentration-dependent manner. Our results indicate that amphiphilic molecules need to be organized in nanosized particles to match the local curvature of the membrane for facilitated uptake. To pursue this hypothesis, other surfactants and biological membranes should be studied in the future for more general conclusions.

Organ and tissue damage can result from injury and disease. How to facilitate regeneration from damage has been a topic for centuries, and still, we are trying to find agents to use for treatments. Two groups of biological substances are known to facilitate wound healing. Phytochemicals with bioactive properties form one group. Many phytochemicals have anti-inflammatory effects and enhance wound healing. Recent studies have described their effects at the gene and protein expression levels, highlighting the receptors and signaling pathways involved. The extremely large number of phytochemicals and the multiple types of receptors they activate suggest a broad range of applicability for their clinical use. The hydrophobic nature of many phytochemicals and the difficulty with chemical stabilization have been a problem. Recent developments in biotechnology and nanotechnology methods are enabling researchers to overcome these problems. The other group of biological substances is extracellular vesicles (EVs), which are now known to have important biological functions, including the improvement of wound healing. The proteins and nanoparticles contained in mammalian EVs as well as the specificity of the targets of microRNAs included in the EVs are becoming clear. Plant-derived EVs have been found to contain phytochemicals. The overlap in the wound-healing capabilities of both phytochemicals and EVs and the differences in their nature suggest the possibility of a combinatorial use of the two groups, which may enhance their effects.

The intracellular journey of extracellular vesicles (EVs) cannot be ignored in various biological pathological processes. In this review, the biogenesis, biological functions, uptake pathways, intracellular trafficking routes, and biomedical applications of EVs were highlighted. Endosomal escape is a unique mode of EVs release. When vesicles escape from endosomes, they avoid the fate of fusing with lysosomes and being degraded, thus having the opportunity to directly enter the cytoplasm or other organelles. This escape mechanism is crucial for EVs to deliver specific signals or substances. The intracellular trafficking of EVs after endosomal escape is a complex and significant biological process that involves the coordinated work of various cellular structures and molecules. Through the in-depth study of this process, the function and regulatory mechanism of EVs are fully understood, providing new dimensions for future biomedical diagnosis and treatment.

Extracellular vesicles represent a large heterogeneous class of near and long-distance intercellular communication mediators, released by both prokaryotic and eukaryotic cells. Specifically, the scientific community has shown growing interest in exosomes, which are nano-sized vesicles with an endosomal origin. Not so long ago, the physiological goal of exosome generation was largely unknown and required more investigation; at first, it was hypothesized that exosomes are able to remove excess, reject and unnecessary constituents from cells to preserve cellular homeostasis. However, thanks to recent studies, the central role of exosomes in regulating cellular communication has emerged. Exosomes act as vectors in cell-cell signaling by their cargo, proteins, lipids, and nucleic acids, and influence physiological and pathological processes. The findings on exosomes are widespread in a large spectrum of biomedical applications from diagnosis and prognosis to therapies. In this review, we describe exosome biogenesis and the current methods for their isolation and characterization, emphasizing the role of their cargo in female reproductive processes, from gametogenesis to implantation, and the potential involvement in human female disorders.

Temporomandibular joint osteoarthritis (TMJOA) is a degenerative ailment that causes slow cartilage degeneration, aberrant bone remodeling, and persistent discomfort, leading to a considerable reduction in the patient's life quality. Current treatment options for TMJOA have limited efficacy. This investigation aimed to explore a potential strategy for halting or reversing the progression of TMJOA through the utilization of exosomes (EXOs) derived from urine-derived stem cells (USCs). The USC-EXOs were obtained through microfiltration and ultrafiltration techniques, followed by their characterization using particle size analysis, electron microscopy, and immunoblotting. Subsequently, an in vivo model of TMJOA induced by mechanical force was established. To assess the changes in the cartilage of TMJOA treated with USC-EXOs, we performed histology analysis using hematoxylin-eosin staining, immunohistochemistry, and histological scoring. Our findings indicate that the utilization of USC-EXOs yields substantial reductions in TMJOA, while concurrently enhancing the structural integrity and smoothness of the compromised condylar cartilage surface. Additionally, USC-EXOs exhibit inhibitory effects on osteoclastogenic activity within the subchondral bone layer of the condylar cartilage, as well as attenuated apoptosis in the rat TMJ in response to mechanical injury. In conclusion, USC-EXOs hold considerable promise as a potential therapeutic intervention for TMJOA.