Controlled Stimulus-Responsive Delivery Systems for Osteoarthritis Treatment DOI Open Access
Qianwen Ye,

Mingshuo Zhang,

Shuyue Li

и другие.

International Journal of Molecular Sciences, Год журнала: 2024, Номер 25(21), С. 11799 - 11799

Опубликована: Ноя. 2, 2024

Osteoarthritis (OA), a common and disabling degenerative joint disease, affects millions of people worldwide imposes considerable burden on patients society due to its high prevalence economic costs. The pathogenesis OA is closely related the progressive degradation articular cartilage accompany inflammation; however, itself cannot heal modulate inflammation lack nerves, blood vessels, lymph-vessels. Therefore, reliable effective methods treat remain highly desired. Local administration drugs or bioactive materials by intra-articular injection delivery system represents promising approach OA, especially considering prolonged retention, chondrocytes targeting, stimuli-responsive release achieve precision therapy. This article summarizes discusses advances in currently used systems (nanoparticle, hydrogel, liposome, microsphere) then focuses their applications treatment from perspective endogenous stimulus (redox reactions, pH, enzymes, temperature) exogenous (near-infrared, magnetic, ultrasound)-responsive release. Finally, challenges potential future directions for development nano-delivery are summarized.

Язык: Английский

Current Knowledge and Future Perspectives of Exosomes as Nanocarriers in Diagnosis and Treatment of Diseases DOI Creative Commons
Zaijun Zou, Li Han, Gang Xu

и другие.

International Journal of Nanomedicine, Год журнала: 2023, Номер Volume 18, С. 4751 - 4778

Опубликована: Авг. 1, 2023

Abstract: Exosomes, as natural nanocarriers, characterized with low immunogenicity, non-cytotoxicity and targeted delivery capability, which have advantages over synthetic nanocarriers. Recently, exosomes shown great potential diagnostic markers for diseases are also considered a promising cell-free therapy. Engineered significantly enhanced the efficacy precision of delivering therapeutic agents, currently being extensively employed in investigations various ailments, including oncology, inflammatory disorders, degenerative conditions. Particularly, engineered enable agent loading, modification, evasion MPS phagocytosis, intelligent control, bioimaging, been developed multifunctional nano-delivery platforms recent years. The utilization bioactive scaffolds that loaded exosome has to substantially augment retention, extend release, enhance efficacy. This approach advanced from conventional hydrogels nanocomposite hydrogels, nanofiber 3D printing, resulting superior physical biological properties effectively address limitations scaffolds. Additionally, plant-derived exosomes, can participate gut flora remodeling via oral administration, an ideal platform treatment intestinal diseases. Consequently, there is interest nanocarriers applications. comprehensive review provides overview biogenesis, composition, isolation methods exosomes. it examines pathological mechanisms diseases, tumors, Furthermore, this highlights significance microbial-derived Strategies specific applications scaffold-loaded further summarized, especially some new techniques such large-scale loading technique, macromolecular development nano-scaffold-loaded delivery. benefits using gut-related discussed. challenges, opportunities, prospects exosome-based disease diagnosis summarized both preclinical clinical viewpoints. Keywords: diagnosis,

Язык: Английский

Процитировано

43

Injectable photocrosslinking spherical hydrogel-encapsulated targeting peptide-modified engineered exosomes for osteoarthritis therapy DOI Creative Commons
Junlai Wan, Zhiyi He,

Renpeng Peng

и другие.

Journal of Nanobiotechnology, Год журнала: 2023, Номер 21(1)

Опубликована: Авг. 21, 2023

Osteoarthritis (OA) is a common degenerative joint disease urgently needing effective treatments. Bone marrow mesenchymal stromal cell-derived exosomes (Exo) are considered good drug carriers whereas they have limitations such as fast clearance and low retention. This study aimed to overcome the of Exo in delivery using multiple strategies. Novel photocrosslinking spherical gelatin methacryloyl hydrogel (GelMA)-encapsulated cartilage affinity WYRGRL (W) peptide-modified engineered were developed for OA treatment performance (W-Exo@GelMA) loaded with small inhibitor LRRK2-IN-1 (W-Exo-L@GelMA) was investigated vitro vivo. The W-Exo-L@GelMA showed an targeting effect on chondrocytes pronounced action suppressing catabolism promoting anabolism vitro. Moreover, remarkably inhibited OA-related inflammation immune gene expression, rescuing IL-1β-induced transcriptomic responses. With enhanced retention joint, demonstrated superior anti-OA activity repair ability murine model. therapeutic validated cultured human cartilage. In conclusion, hydrogel-encapsulated exhibit notable potential therapy. Engineering by series strategies cartilage-targeting Exo-mediated may offer novel strategy treatment.Clinical trial registration: Not applciable.

Язык: Английский

Процитировано

42

Extracellular Vesicles and Hydrogels: An Innovative Approach to Tissue Regeneration DOI Creative Commons
Amir Hashemi,

Masoumeh Ezati,

Minoo Partovi Nasr

и другие.

ACS Omega, Год журнала: 2024, Номер 9(6), С. 6184 - 6218

Опубликована: Янв. 31, 2024

Extracellular vesicles have emerged as promising tools in regenerative medicine due to their inherent ability facilitate intercellular communication and modulate cellular functions. These nanosized transport bioactive molecules, such proteins, lipids, nucleic acids, which can affect the behavior of recipient cells promote tissue regeneration. However, therapeutic application these is frequently constrained by rapid clearance from body inability maintain a sustained presence at injury site. In order overcome obstacles, hydrogels been used extracellular vesicle delivery vehicles, providing localized controlled release system that improves efficacy. This Review will examine role vesicle-loaded regeneration, discussing potential applications, current challenges, future directions. We investigate origins, composition, characterization techniques vesicles, focusing on recent advances exosome profiling machine learning this field. addition, we properties make them ideal carriers. Recent studies utilizing combination for regeneration be highlighted, comprehensive overview research landscape

Язык: Английский

Процитировано

12

Pain Management Strategies in Osteoarthritis DOI Creative Commons
Luca Farinelli, Michele Riccio, Antonio Gigante

и другие.

Biomedicines, Год журнала: 2024, Номер 12(4), С. 805 - 805

Опубликована: Апрель 4, 2024

Pain is the major symptom of osteoarthritis (OA) and an important factor in strategies to manage this disease. However, current standard care does not provide satisfactory pain relief for many patients. The pathophysiology OA complex, its presentation as a clinical syndrome associated with pathologies multiple joint tissues. Treatment options are generally classified pharmacologic, nonpharmacologic, surgical, complementary and/or alternative, typically used combination achieve optimal results. goals treatment alleviation symptoms improvement functional status. Several studies exploring various directions management, including tissue regeneration techniques, personalized medicine, targeted drug therapies. aim present narrative review extensively describe all treatments available practice, further describing most innovative Advancements understanding molecular genetic aspects may lead more effective tailored approaches future.

Язык: Английский

Процитировано

9

Exosomes derived from miR-146a-overexpressing fibroblast-like synoviocytes in cartilage degradation and macrophage M1 polarization: a novel protective agent for osteoarthritis? DOI Creative Commons
Huan Wang, Yue Zhang, Chengfei Zhang

и другие.

Frontiers in Immunology, Год журнала: 2024, Номер 15

Опубликована: Май 23, 2024

Introduction Pathological changes in the articular cartilage (AC) and synovium are major manifestations of osteoarthritis (OA) strongly associated with pain functional limitations. Exosome-derived microRNAs (miRNAs) crucial regulatory factors intercellular communication can influence progression OA by participating degradation chondrocytes phenotypic transformation polarization synovial macrophages. However, specific relationships pathways action exosomal miRNAs pathological both remain unclear. Methods This study evaluates effects fibroblast-like synoviocyte (FLS)-derived exosomes (FLS-Exos), influenced miR-146a, on AC macrophage polarization. We investigated targeted relationship between miR-146a TRAF6, vivo vitro , along involvement NF-κB signaling pathway. Results The expression rats was significantly higher than healthy rats. In upregulation reduced chondrocyte apoptosis, whereas its downregulation had opposite effect. derived from miR-146a-overexpressing FLSs (miR-146a-FLS-Exos) injury apoptosis OA. Furthermore, proliferation reduced, macrophages shifted M1 to M2. Mechanistically, TRAF6 inhibited targeting thereby modulating Toll-like receptor 4/TRAF6/NF-κB pathway innate immune response. Discussion These findings suggest that mediated through FLS-Exos, may alleviate polarization, implicating insights highlight therapeutic potential as a protective agent OA, underscoring importance pathogenesis treatment disease.

Язык: Английский

Процитировано

8

Mesenchymal Stem Cell-Derived Exosomes as a Treatment Option for Osteoarthritis DOI Open Access

Anupama Vadhan,

Tanvi Gupta, Wen‐Li Hsu

и другие.

International Journal of Molecular Sciences, Год журнала: 2024, Номер 25(17), С. 9149 - 9149

Опубликована: Авг. 23, 2024

Osteoarthritis (OA) is a leading cause of pain and disability worldwide in elderly people. There critical need to develop novel therapeutic strategies that can effectively manage improve the quality life for older Mesenchymal stem cells (MSCs) have emerged as promising cell-based therapy age-related disorders due their multilineage differentiation strong paracrine effects. Notably, MSC-derived exosomes (MSC-Exos) gained significant attention because they recapitulate MSCs into benefits without causing any associated risks compared with direct cell transplantation. These help transport bioactive molecules such proteins, lipids, nucleic acids, which influence various cellular processes related tissue repair, regeneration, immune regulation. In this review, we provided an overview MSC-Exos considerable treatment option osteoarthritis. This review will go over underlying mechanisms by may alleviate pathological hallmarks OA, cartilage degradation, synovial inflammation, subchondral bone changes. Furthermore, summarized current preclinical evidence highlighted results from vitro vivo studies, well progress clinical trials using treat OA.

Язык: Английский

Процитировано

8

Potential and challenges of utilizing exosomes in osteoarthritis therapy (Review) DOI Creative Commons
Xuesong Chen,

Bin Tian,

Yiqun Wang

и другие.

International Journal of Molecular Medicine, Год журнала: 2025, Номер 55(3)

Опубликована: Янв. 8, 2025

Exosomes are integral to the pathophysiology of osteoarthritis (OA) due their roles in mediating intercellular communication and regulating inflammatory processes. transport bioactive molecules, such as proteins, lipids nucleic acids, which can influence chondrocyte behavior joint homeostasis. Given properties regeneration ability target damaged tissues, exosomes represent a promising therapeutic avenue for OA treatment. have potential promoting cartilage repair, reducing inflammation improving overall function. However, several challenges remain, including need standardized isolation characterization methods, variability exosomal content, regulatory hurdles. The present review aims provide comprehensive overview current understanding exosome mechanisms potential, while also addressing ongoing faced translating these findings into clinical practice. By consolidating existing research, pave way future studies aimed at optimizing exosome‑based therapies effective management.

Язык: Английский

Процитировано

1

Knee adipose tissue: from its implication in osteoarthritis to its supposed role in tissue engineering DOI Creative Commons
Elena Stocco, Aron Emmi, Raffaele De

и другие.

npj Aging, Год журнала: 2025, Номер 11(1)

Опубликована: Фев. 3, 2025

Knee osteoarthritis (OA) has long been considered as a cartilage disease. However, it is now well established that defects are the ultimate OA feature only. Several studies investigating mechanisms of onset/progression have recognized infrapatellar fat pad an active OA-player but also possible source stem cells with regenerative potential for cartilage. Is really like that? cautious approach should be adopted.

Язык: Английский

Процитировано

1

Standardized Reporting of Research on Exosomes to Ensure Rigor and Reproducibility DOI
Anita Yadav, Yi Xuan, Chandan K. Sen

и другие.

Advances in Wound Care, Год журнала: 2024, Номер 13(11), С. 584 - 599

Опубликована: Июнь 18, 2024

Significance: The study of extracellular vesicles (EV), especially exosomes, has unlocked new avenues in understanding cellular communication and potential therapeutic avenues. Recent Advances: Advancements EV research have shown significant contributions from the International Society for Extracellular Vesicles (ISEV), establishing methodological standards. evolution MISEV guidelines 2014 to 2023 reflects enhanced rigor reproducibility. launch EV-TRACK platform promotes uniformity reproducibility by providing a centralized repository data sharing standardization practices. Furthermore, databases like EVpedia ExoCarta facilitated collaboration within scientific community. Concurrently, exosome-based therapies emerged as forefront area regenerative medicine targeted drug delivery, showcasing exosomes promoting tissue regeneration. Critical Issues: Despite advancements, field grapples with challenges such vesicular heterogeneity, isolation complexity, standardization. These issues impact clinical applications. inconsistency exosomal preparations trials poses efficacy safety. Future Directions: review outlines critical areas future research, including need technological innovation characterization, establishment standardized protocols, deeper exosome biology. also highlights reassess guidelines, develop characterization technologies, establish protocols overcome current limitations. Emphasis is placed on interdisciplinary address complexities biology, improve trial design, ultimately realize exosome's diagnostic potential. Continued evaluation rigorous validation are essential successful integration.

Язык: Английский

Процитировано

7

Engineered Exosomes with ATF5-Modified mRNA Loaded in Injectable Thermogels Alleviate Osteoarthritis by Targeting the Mitochondrial Unfolded Protein Response DOI

Tiancong Ma,

Guangyu Xu, Tian Gao

и другие.

ACS Applied Materials & Interfaces, Год журнала: 2024, Номер 16(17), С. 21383 - 21399

Опубликована: Апрель 16, 2024

Osteoarthritis (OA) progression is highly associated with chondrocyte mitochondrial dysfunction and disorders of catabolism anabolism the extracellular matrix (ECM) in articular cartilage. The unfolded protein response (UPRmt), which an integral component quality control (MQC) system, essential for maintaining homeostasis. We successfully validated pivotal role activating transcription factor 5 (ATF5) upregulating UPRmt, mitigating IL-1β-induced inflammation dysfunction, promoting balanced metabolism cartilage ECM, proving its potential as a promising therapeutic target OA. Modified mRNAs (modRNAs) have emerged novel efficient gene delivery vectors nucleic acid approaches. In this study, we combined Atf5-modRNA (modAtf5) engineered exosomes derived from bone mesenchymal stem cells (ExmodAtf5) to exert cytoprotective effects on chondrocytes via Atf5. However, rapid localized metabolization ExmodAtf5 limits application. PLGA–PEG-PLGA (Gel), injectable thermosensitive hydrogel, was used carrier (Gel@ExmodAtf5) achieve sustained release ExmodAtf5. vitro vivo, use Gel@ExmodAtf5 shown be effective strategy OA treatment. vivo effect evidenced by preservation intact surface, low OARSI scores, fewer osteophytes, mild subchondral sclerosis cystic degeneration. Consequently, combination could significantly enhance efficacy prolong exosome release. addition, protease ClpP enhanced autophagy modulating mTOR/Ulk1 pathway. As result our research, can considered at alleviating

Язык: Английский

Процитировано

6