Injectable Microgels with Hybrid Exosomes of Chondrocyte‐Targeted FGF18 Gene‐Editing and Self‐Renewable Lubrication for Osteoarthritis Therapy

Advanced Materials, Journal Year: 2024, Volume and Issue: 36(16)

Published: Jan. 24, 2024

Abstract Abnormal silencing of fibroblast growth factor (FGF) signaling significantly contributes to joint dysplasia and osteoarthritis (OA); However, the clinical translation FGF18‐based protein drugs is hindered by their short half‐life, low delivery efficiency need for repeated articular injections. This study proposes a CRISPR/Cas9‐based approach effectively activate FGF18 gene OA chondrocytes at genome level in vivo, using chondrocyte‐affinity peptide (CAP) incorporated hybrid exosomes (CAP/FGF18‐hyEXO) loaded with an FGF18‐targeted gene‐editing tool. Furthermore, CAP/FGF18‐hyEXO are encapsulated methacrylic anhydride‐modified hyaluronic (HAMA) hydrogel microspheres via microfluidics photopolymerization create injectable microgel system (CAP/FGF18‐hyEXO@HMs) self‐renewable hydration layers provide persistent lubrication response frictional wear. Together, CAP/FGF18‐hyEXO@HMs, combined vivo editing continuous lubrication, have demonstrated capacity synergistically promote cartilage regeneration, decrease inflammation, prevent ECM degradation both vitro holding great potential translation.

Language: Английский

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Exosomes: a review of biologic function, diagnostic and targeted therapy applications, and clinical trials

Journal of Biomedical Science, Journal Year: 2024, Volume and Issue: 31(1)

Published: July 11, 2024

Abstract Exosomes are extracellular vesicles generated by all cells and they carry nucleic acids, proteins, lipids, metabolites. They mediate the exchange of substances between cells,thereby affecting biological properties activities recipient cells. In this review, we briefly discuss composition exocomes exosome isolation. We also review clinical applications exosomes in cancer biology as well strategies exosome-mediated targeted drug delivery systems. Finally, application context therapeutics both practice literature discussed.

Language: Английский

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The application of extracellular vesicles in orthopedic diseases

Deleted Journal, Journal Year: 2024, Volume and Issue: 2(3)

Published: March 13, 2024

Abstract Orthopedic diseases, such as osteoarthritis and fractures, place a significant burden on individuals healthcare systems worldwide. Extracellular vesicles (EVs), which are membrane‐derived particles, have emerged novel tool in the field of orthopedics. EVs play crucial role diagnosing, regenerating, treating orthopedic diseases. In terms diagnosis, serve potential biomarkers, carrying unique donor cell information circulating effectively bodily fluids. Specific biomolecules within EVs, including proteins, nucleic acids, microRNAs, hold promise biological markers for early detection monitoring shown promoting bone cartilage regeneration. They can enhance tissue regeneration by stimulating various stem cells to proliferate, migrate, differentiate into mature chondrocytes osteocytes. also target specific tissues, making them attractive candidates drug delivery efficiently deliver therapeutic cargo, anti‐inflammatory agents growth factors, affected sites, enhancing treatment efficacy while minimizing toxicity adverse effects. conclusion,

Language: Английский

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Stem cell recruitment polypeptide hydrogel microcarriers with exosome delivery for osteoarthritis treatment

Journal of Nanobiotechnology, Journal Year: 2024, Volume and Issue: 22(1)

Published: Aug. 27, 2024

With the accelerated aging tendency, osteoarthritis (OA) has become an intractable global public health challenge. Stem cells and their derivative exosome (Exo) have shown great potential in OA treatment. Research this area tends to develop functional microcarriers for stem cell Exo delivery improve therapeutic effect. Herein, we a novel system of Exo-encapsulated cell-recruitment hydrogel from liquid nitrogen-assisted microfluidic electrospray Benefited advanced droplet generation capability microfluidics mild cryogelation procedure, resultant particles show uniform size dispersion excellent biocompatibility. Moreover, acryloylated recruitment peptides SKPPGTSS are directly crosslinked within by ultraviolet irradiation, thus simplifying peptide coupling process preventing its premature release. The SKPPGTSS-modified can recruit endogenous promote cartilage repair released further enhances performance through synergistic effects. These features suggest that proposed microcarrier is promising candidate

Language: Английский

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Intra‐Articular Injection of Nanomaterials for the Treatment of Osteoarthritis: From Lubrication Function Restoration to Cell and Gene Therapy

Advanced Functional Materials, Journal Year: 2024, Volume and Issue: 34(30)

Published: May 1, 2024

Abstract Osteoarthritis (OA), a prevalent joint disease affecting many people globally, presents significant challenge in current treatments, which often only manage symptoms without halting progression. This review illuminates novel approaches OA therapy, focusing mainly on intra‐articular injection of nanomaterials. The innovative materials, designed to either mimic or augment natural lubrication, show promise restoring biomechanics and alleviating pain. delves into an array biomimetic lubricants, including polymer brush, nanocomposite hydrogel, nanoparticles, underscoring their roles anti‐inflammation, targeting, cartilage repair, drug delivery. Furthermore, the potential mesenchymal stem cells differentiate chondrocytes, coupled with delivery these exosomes via nanomaterials, has promoted cell therapy avenues for OA. also highlights function non‐coding RNAs such as miRNA, siRNA, circRNA, lncRNA, antisense oligonucleotides impeding progression, nanomaterials facilitating delivery, thus advanced therapeutic possibilities immune evasion bone proliferation. Overall, this encapsulates evolution treatment from material cell, ultimately gene forecasting future where evolve toward integrated, personalized diagnostics therapeutics

Language: Английский

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Charge‐Reversed Exosomes for Targeted Gene Delivery to Cartilage for Osteoarthritis Treatment

Small Methods, Journal Year: 2024, Volume and Issue: 8(9)

Published: April 12, 2024

Abstract Gene therapy has the potential to facilitate targeted expression of therapeutic proteins promote cartilage regeneration in osteoarthritis (OA). The dense, avascular, aggrecan‐glycosaminoglycan (GAG) rich negatively charged cartilage, however, hinders their transport reach chondrocytes effective doses. While viral vector mediated gene delivery shown promise, concerns over immunogenicity and tumorigenic side‐effects persist. To address these issues, this study develops surface‐modified cartilage‐targeting exosomes as non‐viral carriers for therapy. Charge‐reversed cationic are engineered mRNA by anchoring targeting optimally arginine‐rich motifs into anionic exosome bilayer using buffer pH a charge‐reversal switch. Cationic penetrated through full‐thickness early‐stage arthritic human owing weak‐reversible ionic binding with GAGs efficiently delivered encapsulated eGFP residing tissue deep layers, while unmodified do not. When intra‐articularly injected destabilized medial meniscus mice knees OA, loaded charge‐reversed overcame joint clearance rapidly creating an intra‐tissue depot expressing eGFP; native remained unsuccessful. thus hold strong translational platform technology cartilage‐targeted any relevant targets OA treatment.

Language: Английский

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Application of mesenchymal stem cells derived from the umbilical cord or Wharton’s jelly and their extracellular vesicles in the treatment of various diseases

Tissue and Cell, Journal Year: 2024, Volume and Issue: 89, P. 102415 - 102415

Published: May 27, 2024

Language: Английский

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Precise Lubrication and Protection of Cartilage Damage by Targeting Hydrogel Microsphere

Advanced Materials, Journal Year: 2024, Volume and Issue: unknown

Published: Aug. 18, 2024

Abstract Osteoarthritis (OA) is a degenerative bone and joint disease characterized by decreased cartilage lubrication, leading to continuous wear ultimately irreversible damage. This situation particularly challenging for early‐stage OA, as current bio‐lubricants lack precise targeting small inflammatory lesions. In this work, an antibody‐mediated hydrogel microspheres (HMS) developed precisely lubricate the local injury site of prevent progression early OA. Anti‐Collagen type I (Anti‐Col1) antibody that targets sites in OA stages. It anchored on HMS matrix made Gelatin methacrylate (GelMA) poly (sulfobetaine methacrylate) (PSBMA) create targeted (T‐G/S HMS). The T‐G/S HMS's high hydrophilicity, along with dynamic interaction between its surficial Anti‐Col1 Col1 site, ensures effective lubrication Consequently, injecting into rats significantly slows reduces symptoms. conclusion, injectable lubricating strategy represent promising, convenient technique treating slowing progression.

Language: Английский

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Microenvironment Remodeling Self-Healing Hydrogel for Promoting Flap Survival

Biomaterials Research, Journal Year: 2024, Volume and Issue: 28

Published: Jan. 1, 2024

Random flap grafting is a routine procedure used in plastic and reconstructive surgery to repair reconstruct large tissue defects. Flap necrosis primarily caused by ischemia–reperfusion injury inadequate blood supply the distal flap. Ischemia–reperfusion leads production of excessive reactive oxygen species, creating pathological microenvironment that impairs cellular function angiogenesis. In this study, we developed remodeling self-healing hydrogel [laminarin–chitosan-based hydrogel-loaded extracellular vesicles ceria nanozymes (LCH@EVs&CNZs)] improve synergistically promote regeneration survival. The natural (LCH) was created oxidation laminarin carboxymethylated chitosan via Schiff base reaction. We loaded with CNZs EVs. are class nanomaterials enzymatic activity known for their strong scavenging capacity thus alleviating oxidative stress. EVs cell-secreted vesicular structures containing thousands bioactive substances can cell proliferation, migration, differentiation, constructed LCH@EVs&CNZs demonstrated robust excess thereby conferring protection stress environments. Moreover, these constructs notably enhance migration Our results demonstrate effectively remodel skin marked This approach introduces new therapeutic strategy combining microenvironmental EV therapy, which holds promise promoting

Language: Английский

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Engineered MSC‐sEVs as a Versatile Nanoplatform for Enhanced Osteoarthritis Treatment via Targeted Elimination of Senescent Chondrocytes and Maintenance of Cartilage Matrix Metabolic Homeostasis

Advanced Science, Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 4, 2025

Abstract Chondrocyte senescence is an important pathogenic factor causing osteoarthritis (OA) progression through persistently producing pro‐inflammatory factors. Mesenchymal stem cells‐derived small extracellular vesicles (MSC‐sEVs) have shown anti‐inflammatory effects in OA models, while persistent existence of senescent chondrocytes still promotes cartilage destruction. Therefore, improving the targeted elimination ability on required to facilitate translation MSC‐sEVs treatment. In this study, versatile engineered are developed targetedly clear and maintain metabolic homeostasis. Specifically, loaded with siRNA mouse double minute 2 homologue (siMDM2) modified cartilage‐targeting peptide WYRGRL‐PEG 2K ‐DSPE (WPD), named WPD‐sEVs siMDM2 . The results demonstrate modification improves cellular uptake chondrocytes, thus antiaging effects. Importantly, multifunctional enhances penetration extends joint retention time MSC‐sEVs. both post‐traumatic mice naturally aged mice, more effectively eliminates maintained matrix By using P53 phosphorylation inhibitor, essential role MDM2‐P53 pathway function verified. ex vivo cultured human explants, it confirmed that alleviates phenotype. Altogether, findings suggest promising translational potential for

Language: Английский

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