Nerve Growth Factor-Laden Anisotropic Silk Nanofiber Hydrogels to Regulate Neuronal/Astroglial Differentiation for Scarless Spinal Cord Repair

ACS Applied Materials & Interfaces, Journal Year: 2022, Volume and Issue: 14(3), P. 3701 - 3715

Published: Jan. 10, 2022

Scarless spinal cord regeneration remains a challenge due to the complicated microenvironment at lesion sites. In this study, nerve growth factor (NGF) was immobilized in silk protein nanofiber hydrogels with hierarchical anisotropic microstructures fabricate bioactive systems that provide multiple physical and biological cues address injury (SCI). The NGF maintained bioactivity inside regulated neuronal/astroglial differentiation of neural stem cells. aligned facilitated migration orientation cells, which further stimulated angiogenesis neuron extensions both vitro vivo. severe rat long-span hemisection SCI model, these hydrogel matrices reduced scar formation achieved scarless repair effective recovery motor functions. Histological analysis confirmed directional regenerated neuronal tissues, similar morphology normal cord. vivo results showed promising utility for NGF-laden while also demonstrating feasibility cell-free regulate endogenous cell responses.

Language: Английский

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The Exosome-Mediated PI3K/Akt/mTOR Signaling Pathway in Neurological Diseases

Pharmaceutics, Journal Year: 2023, Volume and Issue: 15(3), P. 1006 - 1006

Published: March 21, 2023

As major public health concerns associated with a rapidly growing aging population, neurodegenerative diseases (NDDs) and neurological are important causes of disability mortality. Neurological affect millions people worldwide. Recent studies have indicated that apoptosis, inflammation, oxidative stress the main players NDDs critical roles in processes. During aforementioned inflammatory/apoptotic/oxidative procedures, phosphoinositide 3-kinase (PI3K)/protein kinase B (Akt)/mammalian target rapamycin (mTOR) pathway plays crucial role. Considering functional structural aspects blood–brain barrier, drug delivery to central nervous system is relatively challenging. Exosomes nanoscale membrane-bound carriers can be secreted by cells carry several cargoes, including proteins, nucleic acids, lipids, metabolites. significantly take part intercellular communications due their specific features low immunogenicity, flexibility, great tissue/cell penetration capabilities. Due ability cross these nano-sized structures been introduced as proper vehicles for multiple studies. In present systematic review, we highlight potential therapeutic effects exosomes context targeting PI3K/Akt/mTOR signaling pathway.

Language: Английский

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Multimodal therapy strategy based on a bioactive hydrogel for repair of spinal cord injury

Biomaterials, Journal Year: 2023, Volume and Issue: 299, P. 122160 - 122160

Published: May 11, 2023

Language: Английский

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A swift expanding trend of extracellular vesicles in spinal cord injury research: a bibliometric analysis

Journal of Nanobiotechnology, Journal Year: 2023, Volume and Issue: 21(1)

Published: Aug. 23, 2023

Abstract Extracellular vesicles (EVs) in the field of spinal cord injury (SCI) have garnered significant attention for their potential applications diagnosis and therapy. However, no bibliometric assessment has been conducted to evaluate scientific progress this area. A search articles Web Science (WoS) from January 1, 1991, May 2023, yielded 359 papers that were analyzed using various online analysis tools. These cited 10,842 times with 30.2 per paper. The number publications experienced explosive growth starting 2015. China United States led research initiative. Keywords divided into 3 clusters, including “Pathophysiology SCI”, “Bioactive components EVs”, “Therapeutic effects EVs SCI”. By integrating average appearing year (AAY) keywords VoSviewer time zone map Citation Explosion CiteSpace, focal point undergone a transformative shift. emphasis moved away pathophysiological factors such as “axon”, “vesicle”, “glial cell” more mechanistic applied domains “activation”, “pathways”, “hydrogels” “therapy”. In conclusions, institutions are expected allocate resources towards EVs-loaded hydrogel therapy utilization innovative materials mitigation.

Language: Английский

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ADSC-Exos enhance functional recovery after spinal cord injury by inhibiting ferroptosis and promoting the survival and function of endothelial cells through the NRF2/SLC7A11/GPX4 pathway

Biomedicine & Pharmacotherapy, Journal Year: 2024, Volume and Issue: 172, P. 116225 - 116225

Published: Feb. 1, 2024

Spinal cord injury (SCI) is a devastating disease that causes major motor, sensory and autonomic dysfunctions. Currently, there lack of effective treatment. In this study, we aimed to investigate the potential mechanisms Exosomes from adipose-derived stem cells (ADSC-Exos) in reducing ferroptosis promoting angiogenesis after spinal injury.

Language: Английский

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Engineered extracellular vesicles for tissue repair and regeneration

Burns & Trauma, Journal Year: 2024, Volume and Issue: 12

Published: Jan. 1, 2024

Abstract Extracellular vesicles (EVs) are heterogeneous membrane-like secreted by living cells that involved in many physiological and pathological processes act as intermediaries of intercellular communication molecular transfer. Recent studies have shown EVs from specific sources regulate tissue repair regeneration delivering proteins, lipids, nucleic acids to target signaling molecules. Nanotechnology breakthroughs facilitated the development exploration engineered for repair. Enhancements through gene editing, surface modification, content modification further improved their therapeutic efficacy. This review summarizes potential regeneration, mechanisms action, research progress regenerative medicine. highlights design logic typical examples explores prospects The aim this is provide new insights into applications, thereby expanding use

Language: Английский

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Bone Marrow Mesenchymal Stem Cell-Derived Exosomes Accelerate Functional Recovery After Spinal Cord Injury by Promoting the Phagocytosis of Macrophages to Clean Myelin Debris

Frontiers in Cell and Developmental Biology, Journal Year: 2021, Volume and Issue: 9

Published: Nov. 8, 2021

Macrophage phagocytosis contributes predominantly to processing central nervous system (CNS) debris and further facilitates neurological function restoration after CNS injury. The aims of this study were evaluate the effect bone marrow mesenchymal stem cells (BMSC)-derived exosomes (BMSC-Exos) on phagocytic capability macrophages clear myelin investigate underlying molecular mechanism during spinal cord injury (SCI) process. This work reveals that monocyte-derived (MDMs) infiltrating into SCI site could efficiently engulf process material. However, ability tissue is compromised SCI. administration BMSC-Exos as an approach for treatment rescue macrophage normal by improving internalization, which beneficial repair, evidenced better axon regrowth increased hindlimb locomotor functional recovery in a rodent model. Examination with revealed promote capacity phagocytose vitro create regenerative microenvironment regrowth. In addition, we confirmed BMSC-Exo resulted improved engulfed promoting expression receptor collagenous structure (MARCO) macrophages. inhibition MARCO PolyG (a antagonist) impaired clearance at lesion site, leading damage healing conclusion, these data indicated targeting may have therapeutic potential improvement cell-free immune therapy strategy has wide application prospects treatment.

Language: Английский

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Recent advances in nanomaterials for the treatment of spinal cord injury

Materials Today Bio, Journal Year: 2022, Volume and Issue: 18, P. 100524 - 100524

Published: Dec. 17, 2022

Spinal cord injuries (SCIs) are devastating. In SCIs, a powerful traumatic force impacting the spinal results in permanent loss of nerve function below injury level, leaving patient paralyzed and wheelchair-bound for remainder his/her life. Unfortunately, clinical treatment that depends on surgical decompression appears to be unable handle damaged nerves, high-dose methylprednisolone-based therapy is also associated with problems, such as infection, gastrointestinal bleeding, femoral head necrosis, obesity, hyperglycemia. Nanomaterials have opened new avenues SCI treatment. Among them, performance-based nanomaterials derived from variety materials facilitate improvements microenvironment and, some cases, promote neuron regeneration. Nanoparticulate drug delivery systems enable optimization effects bioavailability, thus contributing development novel treatments. The improved efficiency accuracy gene will benefit exploration mechanisms understanding key genes signaling pathways. Herein, we reviewed different types applied summarized their functions advantages provide perspectives future therapies.

Language: Английский

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The promoting effects of activated olfactory ensheathing cells on angiogenesis after spinal cord injury through the PI3K/Akt pathway

Cell & Bioscience, Journal Year: 2022, Volume and Issue: 12(1)

Published: March 4, 2022

The aim of this study was to investigate the pro-angiogenic potential olfactory ensheathing cells (OECs) activated by curcumin (CCM) and lipopolysaccharide (LPS) possible underlying mechanisms.Vascular endothelial or tissues were cultured treated with conditioned medium (CM) extracted from OECs through addition LPS CCM unactivated controls. Concomitantly, assessed in vitro aortic ring sprouting assay, wound healing CCK-8 tube formation assay. Subsequently, co-cultured evaluate their promoting effect on cell proliferation migration following a mechanical scratch. Moreover, spinal cord injury (SCI) model rats established, number vascular structure injured area after SCI observed OEC transplantation. Finally, mechanism investigated western blot analysis phosphorylated kinase expression without MK-2206 (Akt-inhibitor).The present results showed that can effectively promote cells' proliferation, migration, vessel-like formation. Strikingly, several growth factors such as VEGF-A PDGF-AA, which facilitate vessel formation, found be significantly elevated CM. In addition, PI3K/Akt signaling pathway involved events caused CM, displaying higher phosphorylation levels cells. contrast, delivery MK2206 abrogate all positive effects.OECs have angiogenesis improve microenvironment at site when transplanted cord. This potentiated ability provide effects is likely mediated pathway.

Language: Английский

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Self-assembling peptide gels promote angiogenesis and functional recovery after spinal cord injury in rats

Journal of Tissue Engineering, Journal Year: 2022, Volume and Issue: 13

Published: Jan. 1, 2022

Spinal cord injury (SCI) leads to disruption of the blood-spinal barrier, hemorrhage, and tissue edema, which impair blood circulation induce ischemia. Angiogenesis after SCI is an important step in repair damaged tissues, extent angiogenesis strongly correlates with neural regeneration. Various biomaterials have been developed promote signaling pathways, angiogenic self-assembling peptides are useful for producing diverse supramolecular structures tunable functionality. RADA16 (Ac-RARADADARARADADA-NH2), forms nanofiber networks under physiological conditions, a peptide that can provide mechanical support regeneration reportedly has roles wound healing. In this study, we applied injectable form or without neuropeptide substance P contused spinal cords rats examined within subsequent functional improvement. Histological immunohistochemical analyses revealed inflammatory cell population lesion cavity was decreased, vessel number density around were increased, levels neurofilaments increased received (rats RADA16/SP group). Moreover, real-time PCR analysis tissues showed IL-10 expression locomotor function (as assessed by Basso, Beattie, Bresnahan (BBB) scale horizontal ladder test) significantly improved group compared control group. Our findings indicate modified effectively stimulates candidate agent promoting recovery post-SCI.

Language: Английский

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