Progress of Microfluidic Hydrogel‐Based Scaffolds and Organ‐on‐Chips for the Cartilage Tissue Engineering

Advanced Materials, Год журнала: 2023, Номер 35(26)

Опубликована: Янв. 12, 2023

Abstract Cartilage degeneration is among the fundamental reasons behind disability and pain across globe. Numerous approaches have been employed to treat cartilage diseases. Nevertheless, none shown acceptable outcomes in long run. In this regard, convergence of tissue engineering microfabrication principles can allow developing more advanced microfluidic technologies, thus offering attractive alternatives current treatments traditional constructs used applications. Herein, developments involving hydrogel‐based scaffolds, promising structures for regeneration, ranging from hydrogels with channels prepared by devices, that enable therapeutic delivery cells, drugs, growth factors, as well cartilage‐related organ‐on‐chips are reviewed. Thereafter, anatomy types damages, present treatment options briefly overviewed. Various introduced, advantages scaffolds over thoroughly discussed. Furthermore, available technologies fabricating chips presented. The preclinical clinical applications regeneration development time further explained. developments, recent key challenges, prospects should be considered so develop systems repair highlighted.

Язык: Английский

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Regeneration of articular cartilage defects: Therapeutic strategies and perspectives

Journal of Tissue Engineering, Год журнала: 2023, Номер 14

Опубликована: Янв. 1, 2023

Articular cartilage (AC), a bone-to-bone protective device made of up to 80% water and populated by only one cell type (i.e. chondrocyte), has limited capacity for regeneration self-repair after being damaged because its low density, alymphatic avascular nature. Resulting repair defects, such as osteoarthritis (OA), is highly challenging in clinical treatment. Fortunately, the development tissue engineering provides promising method growing cells using hydrogels or porous scaffolds. In this paper, we review therapeutic strategies AC including current treatment methods, engineering/regenerative strategies, recent advances biomaterials, present emphasize on perspectives gene regulation therapy noncoding RNAs (ncRNAs), circular RNA (circRNA) microRNA (miRNA).

Язык: Английский

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Culture-expanded mesenchymal stromal cell therapy: does it work in knee osteoarthritis? A pathway to clinical success

Cellular and Molecular Immunology, Год журнала: 2023, Номер 20(6), С. 626 - 650

Опубликована: Апрель 25, 2023

Abstract Osteoarthritis (OA) is a degenerative multifactorial disease with concomitant structural, inflammatory, and metabolic changes that fluctuate in temporal patient-specific manner. This complexity has contributed to refractory responses various treatments. MSCs have shown promise as multimodal therapeutics mitigating OA symptoms progression. Here, we evaluated 15 randomized controlled clinical trials (RCTs) 11 nonrandomized RCTs using culture-expanded the treatment of knee OA, found net positive effects on pain (improving function 12/15 relative baseline 11/15 control groups at study endpoints) cartilage protection and/or repair (18/21 studies). We examined MSC dose, tissue origin, autologous vs. allogeneic origins well patient phenotype, endotype, age, sex level severity key parameters parsing effectiveness. The relatively small sample size 610 patients limited drawing definitive conclusions. Nonetheless, noted trends toward moderate higher doses select phenotypes leading structural improvements or preservation. Evidence from preclinical studies supportive anti-inflammatory immunomodulatory effects, but additional investigations immunomodulatory, chondroprotective other mechanisms action are needed. hypothesize basal “fitness” correlates efficacy, this hypothesis needs be validated future studies. conclude roadmap articulating need match an subset defined by molecular endotype phenotype basally “fit” engineered-to-be-fit-for-OA well-designed, data-intensive advance field.

Язык: Английский

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Osteoarthritis

Nature Reviews Disease Primers, Год журнала: 2025, Номер 11(1)

Опубликована: Фев. 13, 2025

Язык: Английский

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Engineering of MSC-Derived Exosomes: A Promising Cell-Free Therapy for Osteoarthritis

Membranes, Год журнала: 2022, Номер 12(8), С. 739 - 739

Опубликована: Июль 28, 2022

Osteoarthritis (OA) is characterized by progressive cartilage degeneration with increasing prevalence and unsatisfactory treatment efficacy. Exosomes derived from mesenchymal stem cells play an important role in alleviating OA promoting regeneration, inhibiting synovial inflammation mediating subchondral bone remodeling without the risk of immune rejection tumorigenesis. However, low yield, weak activity, inefficient targeting ability unpredictable side effects natural exosomes have limited their clinical application. At present, various approaches been applied exosome engineering to regulate production function, such as pretreatment parental cells, drug loading, genetic surface modification. Biomaterials also proved facilitate efficient delivery enhance effectiveness. Here, we summarize current understanding biogenesis, isolation characterization exosomes, focus on large-scale preparation engineered well therapeutic potential OA, thus providing novel insights into exploring advanced MSC-derived exosome-based cell-free therapy for OA.

Язык: Английский

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Cartilage regeneration and inflammation modulation in knee osteoarthritis following injection of allogeneic adipose-derived mesenchymal stromal cells: a phase II, triple-blinded, placebo controlled, randomized trial

Stem Cell Research & Therapy, Год журнала: 2023, Номер 14(1)

Опубликована: Июнь 14, 2023

Abstract Background Intra-articular injection of mesenchymal stromal cells (MSCs) with immunomodulatory features and their paracrine secretion regenerative factors proposed a noninvasive therapeutic modality for cartilage regeneration in knee osteoarthritis (KOA). Methods Total number 40 patients KOA enrolled two groups. Twenty received intra-articular 100 × 10 6 allogeneic adipose-derived (AD-MSCs), 20 as control group placebo (normal saline). Questionnaire-based measurements, certain serum biomarkers, some cell surface markers were evaluated 1 year. Magnetic resonance imaging (MRI) before year after was performed to measure possible changes the articular cartilage. Results Forty allocated including 4 men (10%) 36 women (90%) average age 56.1 ± 7.2 years 52.8 7.5 AD-MSCs group. Four (two from group) excluded during study. Clinical outcome measures showed improvement Hyaluronic acid oligomeric matrix protein levels blood decreased significantly who ( P < 0.05). Although IL-10 level increased week 0.05), inflammatory dramatically 3 months 0.001). Expressions CD3, CD4, CD8 have decreasing trend 6-month follow-up 0.001), respectively. However, CD25 + remarkably treatment intervention 0.005). MRI findings slight increase thickness tibial femoral cartilages The significant medial posterior anterior areas ​​the tibia 0.01 0.05, Conclusion Inter-articular is safe. Laboratory data, findings, clinical examination at different time points notable Trial registration : Iranian registry trials (IRCT, https://en.irct.ir/trial/46 ), IRCT20080728001031N23. Registered 24 April 2018.

Язык: Английский

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Mesenchymal stem cell-derived exosomes as a promising cell-free therapy for knee osteoarthritis

Frontiers in Bioengineering and Biotechnology, Год журнала: 2024, Номер 12

Опубликована: Янв. 16, 2024

Osteoarthritis (OA), as a degenerative disease, leads to high socioeconomic burdens and disability rates. The knee joint is typically the most affected characterized by progressive destruction of articular cartilage, subchondral bone remodeling, osteophyte formation synovial inflammation. current management OA mainly focuses on symptomatic relief does not help slow down advancement disease. Recently, mesenchymal stem cells (MSCs) their exosomes have garnered significant attention in regenerative therapy tissue engineering areas. Preclinical studies demonstrated that MSC-derived (MSC-Exos), bioactive factor carriers, promising results cell-free OA. This study reviewed application various MSC-Exos for treatment, along with exploring potential underlying mechanisms. Moreover, strategies future perspectives utilization engineered MSC-Exos, alongside associated challenges, were also discussed.

Язык: 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, Год журнала: 2024, Номер 34(30)

Опубликована: Май 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

Язык: 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, Год журнала: 2025, Номер unknown

Опубликована: Янв. 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

Язык: Английский

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Orthobiologics: a review

International Orthopaedics, Год журнала: 2023, Номер 47(7), С. 1645 - 1662

Опубликована: Апрель 18, 2023

Язык: Английский

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