Bioinspired porous microspheres for sustained hypoxic exosomes release and vascularized bone regeneration

Bioactive Materials, Journal Year: 2022, Volume and Issue: 14, P. 377 - 388

Published: Feb. 1, 2022

Exosomes derived from mesenchymal stem cells (MSCs) have demonstrated regenerative potential for cell-free bone tissue engineering, nevertheless, certain challenges, including the confined therapeutic potency of exosomes and ineffective delivery method, are still persisted. Here, we confirmed that hypoxic precondition could induce enhanced secretion human exfoliated deciduous teeth (SHEDs) via comprehensive proteomics analysis, corresponding (H-Exo) exhibited superior in promoting cellular angiogenesis osteogenesis significant up-regulation focal adhesion, VEGF signaling pathway, thyroid hormone synthesis. Then, developed a platform technology enabling effective with sustained release kinetics to irregular-shaped defects injection. This is based on simple adsorbing technique, where adsorbed onto surface injectable porous poly(lactide-co-glycolide) (PLGA) microspheres bioinspired polydopamine (PDA) coating (PMS-PDA microspheres). The PMS-PDA effectively adsorb exosomes, show H-Exo 21 days high bioactivity, vascularized regeneration 5-mm rat calvarial defect. These findings indicate microsphere-based exosome efficient inducing regeneration, hence facilitating clinical translation exosome-based therapy.

Language: Английский

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Discrepancies on the Role of Oxygen Gradient and Culture Condition on Mesenchymal Stem Cell Fate

Advanced Healthcare Materials, Journal Year: 2021, Volume and Issue: 10(6)

Published: Feb. 2, 2021

Over the past few years, mesenchymal stem (or stromal) cells (MSCs) have garnered enormous interest due to their therapeutic value especially for multilineage differentiation potential leading regenerative medicine applications. MSCs undergo physiological changes upon in vitro expansion resulting expression of different receptors, thereby inducing high variabilities efficacy. Therefore, understanding biochemical cues that influence native local signals on or proliferation these is very important. There been several reports culture low oxygen gradient hypoxic conditions) upregulates stemness markers and promotes cell an undifferentiated state, as hypoxia mimics conditions progenitor experience within tissue. However, studies report gradients causing ambiguity interpretation results. In this progress report, it aimed summarize recent field with specific focus conflicting results reported during application improving MSCs. Further, tried decipher factors can affect characteristics MSC under suggest a techniques could be combined better recapitulate tissue niche.

Language: Английский

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Role of hypoxia preconditioning in therapeutic potential of mesenchymal stem-cell-derived extracellular vesicles

World Journal of Stem Cells, Journal Year: 2022, Volume and Issue: 14(7), P. 453 - 472

Published: July 26, 2022

The use of mesenchymal stem-cells (MSC) in cell therapy has received considerable attention because their properties. These properties include high expansion and differentiation vitro, low immunogenicity, modulation biological processes, such as inflammation, angiogenesis hematopoiesis. Curiously, the regenerative effect MSC is partly due to paracrine activity. This prompted numerous studies, investigate therapeutic potential secretome general, specifically extracellular vesicles (EV). latter contain proteins, lipids, nucleic acids, other metabolites, which can cause physiological changes when released into recipient cells. Interestingly, contents EV be modulated by preconditioning under different culture conditions. Among them, exposure hypoxia stands out; these cells respond activating hypoxia-inducible factor (HIF) at O2 concentrations. HIF direct indirect pleiotropic effects, modulating expression hundreds genes involved processes migration, proliferation, differentiation, angiogenesis, metabolism, apoptosis. Expression reflected secreted EV. studies show that MSC-derived conditioned have a higher capacity than those obtained normoxia. In this review, we implications responses relation tissue regeneration. addition, being evaluated very attractive strategy for isolation EV, with clinical medicine applied pathologies.

Language: Английский

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Tendon tissue engineering: An overview of biologics to promote tendon healing and repair

Journal of Tissue Engineering, Journal Year: 2023, Volume and Issue: 14

Published: Jan. 1, 2023

Tendons are dense connective tissues with a hierarchical polarized structure that respond to and adapt the transmission of muscle contraction forces skeleton, enabling motion maintaining posture. Tendon injuries, also known as tendinopathies, becoming more common populations age participation in sports/leisure activities increases. The tendon has poor ability self-heal regenerate given its intrinsic, constrained vascular supply exposure frequent, severe loading. There is lack understanding underlying pathophysiology, it not surprising disorder-targeted medicines have only been partially effective at best. Recent tissue engineering approaches emerged potential tool drive regeneration healing. In this review, we investigated physiochemical factors involved ontogeny discussed their application vitro reproduce functional self-renewing tissue. We sought understand whether stem cells capable forming tendons, how they can be directed towards tenogenic lineage, growth regulated monitored during entire differentiation path. Finally, showed recent developments engineering, specifically use mesenchymal (MSCs), which differentiate into cells, well role extracellular vesicles (EVs) for accelerating healing response after injury.

Language: Английский

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The Metabolic Changes between Monolayer (2D) and Three-Dimensional (3D) Culture Conditions in Human Mesenchymal Stem/Stromal Cells Derived from Adipose Tissue

Cells, Journal Year: 2023, Volume and Issue: 12(1), P. 178 - 178

Published: Jan. 1, 2023

One of the key factors that may influence therapeutic potential mesenchymal stem/stromal cells (MSCs) is their metabolism. The switch between mitochondrial respiration and glycolysis can be affected by many factors, including oxygen concentration spatial form culture. This study compared metabolic features adipose-derived (ASCs) dedifferentiated fat (DFATs) cultivated as monolayer or spheroid culture under 5% O2 (physiological normoxia) impact on MSCs abilities.We observed cultured spheroids had a slightly lower viability reduced proliferation rate but higher expression stemness-related transcriptional to in monolayer. three-dimensional increased mtDNA content, consumption (OCR) extracellular acidification (ECAR), especially DFATs-3D population. DFATs also demonstrated levels Complex V proteins rates ATP production. Moreover, reactive species intracellular lactic acid were found 3D culture.Our results suggest reconfiguration accompanies transition from 2D processes both become more active. Intensified metabolism might associated with demand for energy, which needed maintain pluripotency genes stemness state.

Language: Английский

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Applications of Stem Cell-Derived Extracellular Vesicles in Nerve Regeneration

International Journal of Molecular Sciences, Journal Year: 2024, Volume and Issue: 25(11), P. 5863 - 5863

Published: May 28, 2024

Extracellular vesicles (EVs), including exosomes, microvesicles, and other lipid derived from cells, play a pivotal role in intercellular communication by transferring information between cells. EVs secreted progenitor stem cells have been associated with the therapeutic effects observed cell-based therapies, they also contribute to tissue regeneration following injury, such as orthopaedic surgery cases. This review explores involvement of nerve regeneration, their potential drug carriers, significance cell research cell-free therapies. It underscores importance bioengineers comprehending manipulating EV activity optimize efficacy engineering regenerative

Language: Английский

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Multifunctional scaffolds for bone repair following age-related biological decline: Promising prospects for smart biomaterial-driven technologies

Biomaterials, Journal Year: 2024, Volume and Issue: 311, P. 122683 - 122683

Published: June 28, 2024

Language: Английский

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Trends in Articular Cartilage Tissue Engineering: 3D Mesenchymal Stem Cell Sheets as Candidates for Engineered Hyaline-Like Cartilage

Cells, Journal Year: 2021, Volume and Issue: 10(3), P. 643 - 643

Published: March 13, 2021

Articular cartilage defects represent an inciting factor for future osteoarthritis (OA) and degenerative joint disease progression. Despite multiple clinically available therapies that succeed in providing short term pain reduction restoration of limited mobility, current treatments do not reliably regenerate native hyaline or halt degeneration at these defect sites. Novel therapeutics aimed addressing limitations clinical regeneration increasingly focus on allogeneic cells, specifically mesenchymal stem cells (MSCs), as potent, banked, cell sources express chondrogenic lineage commitment capabilities. Innovative tissue engineering approaches employing MSCs aim to develop three-dimensional (3D), chondrogenically differentiated constructs direct immediate replacement cartilage, improve local site integration, optimize treatment outcomes. Among emerging technologies, advancements sheet offer promising capabilities achieving both vitro hyaline-like differentiation effective transplantation, based controlled 3D cellular interactions retained adhesion molecules. This review focuses MSC-based fabricating "ready-to-use" rapid vivo regenerative therapies. We highlight directions regarding development MSC-derived therapies, emphasizing engineering, with specific regulating post-differentiation transplantation

Language: Английский

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Electrical stimulation: Effective cue to direct osteogenic differentiation of mesenchymal stem cells?

Biomaterials Advances, Journal Year: 2022, Volume and Issue: 138, P. 212918 - 212918

Published: May 24, 2022

Language: Английский

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Fine‐tuning Dynamic Cross–linking for Enhanced 3D Bioprinting of Hyaluronic Acid Hydrogels

Advanced Functional Materials, Journal Year: 2023, Volume and Issue: 34(4)

Published: Oct. 19, 2023

Abstract 3D bioprinting of stem cells shows promise for medical applications, but the development an efficient bioink remains a challenge. Recently, emergence dynamically cross–linked hydrogels has advanced this field to obtain self‐healing materials. However, more bioinks are needed that display optimum gelling kinetics, viscoelasticity, shear‐thinning property, structural fidelity, and hold printed structures sufficiently long enough allow maturation new tissue. Here, novel extracellular matrix‐based human mesenchymal (hMSCs) is presented. Hyaluronic acid (HA) modified with cysteine aldehyde functional groups, creating dual cross–linking disulfide thiazolidine products. The investigation demonstrates significantly improves hydrogel stability biological properties. exhibits fast gelation shear‐thinning, shape‐maintaining properties, high cell survival after printing >2‐fold increase in stemness marker (OCT3/4 NANOG), supports proliferation migration. Disulfide contributes migration, while reduces time, enhances long‐term stability, proliferation. Overall, HA‐based fulfills requirements successful cells, providing promising solution therapy regenerative medicine.

Language: Английский

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