Extracellular vesicle-loaded hydrogels for tissue repair and regeneration

Materials Today Bio, Journal Year: 2022, Volume and Issue: 18, P. 100522 - 100522

Published: Dec. 21, 2022

Extracellular vesicles (EVs) are a collective term for nanoscale or microscale secreted by cells that play important biological roles. Mesenchymal stem class of with the potential self-healing and multidirectional differentiation. In recent years, numerous studies have shown EVs, especially those mesenchymal cells, can promote repair regeneration various tissues and, thus, significant in regenerative medicine. However, due to rapid clearance capacity circulatory system, EVs barely able act persistently at specific sites target tissues. Hydrogels good biocompatibility loose porous structural properties allow them serve as EV carriers, thereby prolonging retention certain areas slowing release EVs. When needed function sites, EV-loaded hydrogels stand an excellent approach. this review, we first introduce sources, roles, extraction characterization methods describe their current application status. We then review different types discuss factors influencing abilities carry summarize several strategies loading into characterizing hydrogels. Furthermore, applications tissue repair. This article concludes summary state research on outlook future directions, which hope will provide promising ideas researchers.

Language: Английский

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Mesenchymal Stem Cell-Derived Extracellular Vesicles Attenuate Mitochondrial Damage and Inflammation by Stabilizing Mitochondrial DNA

ACS Nano, Journal Year: 2020, Volume and Issue: 15(1), P. 1519 - 1538

Published: Dec. 28, 2020

Mitochondrial dysfunction is a key feature of injury to numerous tissues and stem cell aging. Although the tissue regenerative role mesenchymal (MSC)-derived extracellular vesicles (MSC-EVs) well known, their specific in regulating mitochondrial function target cells remains elusive. Here, we report that MSC-EVs attenuated mtDNA damage inflammation after acute kidney (AKI) this effect was at least partially dependent on transcription factor A (TFAM) pathway. In detail, TFAM were depleted by oxidative stress MSCs from aged or diabetic donors. Higher levels mRNA detected normal control (NC) than TFAM-knockdown (TFAM-KD) EVs. EV-mediated transfer recipient unaffected transcriptional inhibition. Accordingly, application restored protein TFAM-mtDNA complex (nucleoid) stability, thereby reversing deletion phosphorylation (OXPHOS) defects injured renal tubular cells. Loss also led downregulation multiple anti-inflammatory miRNAs proteins MSC-EVs. vivo, intravenously injected EVs primarily accumulated liver, kidney, spleen, lung. lesion formation, damage, mice with AKI, whereas TFAM-KD resulted poor therapeutic outcomes. Moreover, overexpression (TFAM-OE) improved rescue some extent. This study suggests are promising nanotherapeutics for diseases characterized signaling essential maintaining capacity.

Language: Английский

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Extracellular vesicles in kidney disease

Nature Reviews Nephrology, Journal Year: 2022, Volume and Issue: 18(8), P. 499 - 513

Published: May 31, 2022

Language: Английский

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Targeted Therapy for Inflammatory Diseases with Mesenchymal Stem Cells and Their Derived Exosomes: From Basic to Clinics

International Journal of Nanomedicine, Journal Year: 2022, Volume and Issue: Volume 17, P. 1757 - 1781

Published: April 1, 2022

Abstract: Inflammation is a beneficial and physiological process, but there are number of inflammatory diseases which have detrimental effects on the body. In addition, drugs used to treat inflammation toxic side when over long period time. Mesenchymal stem cells (MSCs) pluripotent that can be isolated from variety tissues differentiate into diverse cell types under appropriate conditions. They also exhibit noteworthy anti-inflammatory properties, providing new options for treatment diseases. The therapeutic potential MSCs currently being investigated various diseases, such as kidney injury, lung osteoarthritis (OA), rheumatoid arthritis (RA), bowel disease (IBD). perform multiple functions, including immunomodulation, homing, differentiation, enable damaged form balanced regenerative microenvironment severe accumulated evidence indicates exosomes extracellular vesicles (MSC-Exos) play an extraordinary role, mainly by transferring their components recipient cells. this review, we summarize mechanism clinical trials MSC-Exos in detail, with view contributing Keywords: mesenchymal cells, exosome, clinic data, drug delivery, targeted therapy

Language: Английский

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Nanodrugs alleviate acute kidney injury: Manipulate RONS at kidney

Bioactive Materials, Journal Year: 2022, Volume and Issue: 22, P. 141 - 167

Published: Sept. 29, 2022

Currently, there are no clinical drugs available to treat acute kidney injury (AKI). Given the high prevalence and mortality rate of AKI, development effectively AKI is a huge unmet medical need research hotspot. Although existing evidence fully demonstrates that reactive oxygen nitrogen species (RONS) burst at site major contributor progression, heterogeneity, complexity, unique physiological structure make most antioxidant anti-inflammatory small molecule ineffective because lack targeting side effects. Recently, nanodrugs with intrinsic through control size, shape, surface properties have opened exciting prospects for treatment AKI. Many emerged address limitations current treatments. In this review, we systematically summarized first time about emerging exploit pathological features overcome traditional small-molecule achieve efficacy. First, analyzed structural characteristics main mechanism AKI: hypoxia, harmful substance accumulation-induced RONS renal despite multifactorial initiation heterogeneity Subsequently, introduced strategies used improve reviewed advances nano-RONS-sacrificial agents, nanozymes, nanocarriers antioxidants drugs. These demonstrated excellent therapeutic effects, such as greatly reducing oxidative stress damage, restoring function, low Finally, discussed challenges future directions translating into treatment.

Language: Английский

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Engineering Extracellular Vesicles as Delivery Systems in Therapeutic Applications

Advanced Science, Journal Year: 2023, Volume and Issue: 10(17)

Published: April 20, 2023

Extracellular vesicles (EVs) are transport secreted by living cells and released into the extracellular environment. Recent studies have shown that EVs serve as "messengers" in intercellular inter-organismal communication, both normal pathological processes. EVs, natural nanocarriers, can deliver bioactivators therapy with their endogenous properties. This review article describes engineering of sources, isolation method, cargo loading, boosting approach, adjustable targeting EVs. Furthermore, summarizes recent progress made EV-based delivery systems applications, including cancer, cardiovascular diseases, liver, kidney, nervous system COVID-19 emphasizes obstacles challenges therapies possible strategies.

Language: Английский

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Biotin–Avidin System-Based Delivery Enhances the Therapeutic Performance of MSC-Derived Exosomes

ACS Nano, Journal Year: 2023, Volume and Issue: 17(9), P. 8530 - 8550

Published: April 28, 2023

Exosomes (EXs) shed by mesenchymal stem cells (MSCs) are potent therapeutic agents that promote wound healing and regeneration, but when used alone in vivo, their potency is diminished rapid clearance bioactivity loss. Inspired the biotin-avidin interaction, we developed a simple yet versatile method for immobilization of MSC-derived EXs (MSC-EXs) into hydrogels achieved sustained release regenerative purposes. First, biotin-modified gelatin methacryloyl (Bio-GelMA) was fabricated grafting NHS-PEG12-biotin onto amino groups GelMA. Biotin-modified MSC-EXs (Bio-EXs) were then synthesized using an situ self-assembling biotinylation strategy, which provided sufficient binding sites MSC-EX delivery with little effect on cargo composition. Thereafter, Bio-EXs immobilized Bio-GelMA via streptavidin to generate Bio-GelMA@Bio-EX hydrogels. An vitro analysis demonstrated could be taken up macrophages exerted immunomodulatory effects similar those MSC-EXs, 7 days. After subcutaneous transplantation, more constant retention observed 28 When placed artificial periodontal multitissue defect, functionalized exhibited optimized performance regrow complex tissues, including acellular cementum, ligaments (PDLs), alveolar bone. In this context, robust promoted macrophage polarization toward M2 phenotype. Our findings demonstrate delivered aid system exhibit macrophage-modulating repair-promoting functions suggest universal approach development MSC-EX-functionalized biomaterials advanced therapies.

Language: Английский

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Supramolecular Hydrogel Microspheres of Platelet-Derived Growth Factor Mimetic Peptide Promote Recovery from Spinal Cord Injury

ACS Nano, Journal Year: 2023, Volume and Issue: 17(4), P. 3818 - 3837

Published: Feb. 14, 2023

Neural stem cells (NSCs) are considered to be prospective replacements for neuronal cell loss as a result of spinal cord injury (SCI). However, the survival and differentiation NSCs strongly affected by unfavorable microenvironment induced SCI, which critically impairs their therapeutic ability treat SCI. Herein, strategy fabricate PDGF-MP hydrogel (PDGF-MPH) microspheres (PDGF-MPHM) instead bulk hydrogels is proposed dramatically enhance efficiency platelet-derived growth factor mimetic peptide (PDGF-MP) in activating its receptor. PDGF-MPHM were fabricated piezoelectric ceramic-driven thermal electrospray device, had an average size 9 μm, also activate PDGFRβ more effectively than PDGF-MPH. In vitro, exerted strong neuroprotective effects maintaining proliferation inhibiting apoptosis presence myelin extracts. vivo, inhibited M1 macrophage infiltration extrinsic or intrinsic on seventh day after Eight weeks T10 SCI treatment results showed that + significantly promoted differentiation, reduced lesion size, considerably improved motor function recovery rats stimulating axonal regeneration, synapse formation, angiogenesis comparison with graft group. Therefore, our findings provide insights into promising agent repair.

Language: Английский

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Extracellular vesicle–matrix interactions

Nature Reviews Materials, Journal Year: 2023, Volume and Issue: 8(6), P. 390 - 402

Published: March 17, 2023

Language: Английский

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Targeted therapy of kidney disease with nanoparticle drug delivery materials

Bioactive Materials, Journal Year: 2024, Volume and Issue: 37, P. 206 - 221

Published: March 21, 2024

With the development of nanomedicine, nanomaterials have been widely used, offering specific drug delivery to target sites, minimal side effects, and significant therapeutic effects. The kidneys filtration reabsorption functions, with various potential cell types a complex structural environment, making strategies for kidney function protection recovery after injury complex. This also lays foundation application nanomedicine in diseases. Currently, evidence preclinical clinical settings supports feasibility targeted therapy diseases using based on nanomaterials. prerequisite treating is use carriers good biocompatibility, including nanoparticles, hydrogels, liposomes, micelles, dendrimer polymers, adenoviruses, lysozymes, elastin-like polypeptides. These precise renal uptake, longer half-life, organ distribution, protecting improving efficacy drugs they carry. Additionally, attention should be paid toxicity solubility carriers. While mentioned above used studies both vivo vitro, extensive trials are still needed ensure short-term long-term effects nano human body. review will discuss advantages limitations nanoscale carrier materials diseases, provide more comprehensive catalog nanocarrier materials, offer prospects their drug-loading applications.

Language: Английский

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