Functional Antimicrobial Peptide-loaded 3D Scaffolds for Infected Bone Defect Treatment with AI and Multidimensional Printing

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

Published: Jan. 1, 2024

Infection is the most prevalent complication of fractures, particularly in open and often leads to severe consequences.

Language: Английский

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Mesenchymal Stromal Cells: Heterogeneity and Therapeutical Applications

Cells, Journal Year: 2023, Volume and Issue: 12(16), P. 2039 - 2039

Published: Aug. 10, 2023

Mesenchymal stromal cells nowadays emerge as a major player in the field of regenerative medicine and translational research. They constitute, with their derived products, most frequently used cell type different therapies. However, heterogeneity, including subpopulations, anatomic source isolation, high donor-to-donor variability, constitutes controversial issue that affects use clinical applications. Furthermore, intrinsic extrinsic molecular mechanisms underlying self-renewal fate specification are still not completely elucidated. This review dissects heterogeneity aspects tissue associated distinct developmental origin need to be considered when generating homogenous products before usage for

Language: Английский

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Targeting adipocyte ESRRA promotes osteogenesis and vascular formation in adipocyte-rich bone marrow

Nature Communications, Journal Year: 2024, Volume and Issue: 15(1)

Published: May 4, 2024

Abstract Excessive bone marrow adipocytes (BMAds) accumulation often occurs under diverse pathophysiological conditions associated with deterioration. Estrogen-related receptor α (ESRRA) is a key regulator responding to metabolic stress. Here, we show that adipocyte-specific ESRRA deficiency preserves osteogenesis and vascular formation in adipocyte-rich upon estrogen or obesity. Mechanistically, adipocyte interferes E2/ESR1 signaling resulting transcriptional repression of secreted phosphoprotein 1 ( Spp1 ); yet positively modulates leptin expression by binding its promoter. abrogation results enhanced SPP1 decreased secretion from both visceral BMAds, concertedly dictating stromal stem cell fate commitment restoring type H vessel formation, constituting feed-forward loop for formation. Pharmacological inhibition protects obese mice against loss high adiposity. Thus, our findings highlight therapeutic approach via targeting preserve especially detrimental milieu.

Language: Английский

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Bioinspired artificial antioxidases for efficient redox homeostasis and maxillofacial bone regeneration

Nature Communications, Journal Year: 2025, Volume and Issue: 16(1)

Published: Jan. 20, 2025

Abstract Reconstructing large, inflammatory maxillofacial defects using stem cell-based therapy faces challenges from adverse microenvironments, including high levels of reactive oxygen species (ROS), inadequate oxygen, and intensive inflammation. Here, inspired by the reaction mechanisms intracellular antioxidant defense systems, we propose de novo design an artificial antioxidase Ru-doped layered double hydroxide (Ru-hydroxide) for efficient redox homeostasis bone regeneration. Our studies demonstrate that Ru-hydroxide consists hydroxyls-synergistic monoatomic Ru centers, which efficiently react with collaborate hydroxyls rapid proton electron transfer, thus exhibiting efficient, broad-spectrum, robust ROS scavenging performance. Moreover, can effectively sustain cell viability osteogenic differentiation in elevated environments, modulating microenvironment during tissue regeneration male mice. We believe this development offers a promising avenue designing antioxidase-like materials to treat various inflammation-associated disorders, arthritis, diabetic wounds, enteritis, fractures.

Language: Английский

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New Advances in Periodontal Functional Materials Based on Antibacterial, Anti‐Inflammatory, and Tissue Regeneration Strategies

Advanced Healthcare Materials, Journal Year: 2025, Volume and Issue: unknown

Published: Feb. 2, 2025

With the global population aging, awareness of oral health is rising. Periodontitis, a widespread bacterial infectious disease, gaining attention. Current novel biomaterials address key clinical issues like infection, gum inflammation, tooth loosening, and loss, focusing on antibacterial, anti-inflammatory, tissue regeneration properties. However, strategies that integrate advantages these to achieve synergistic therapeutic effects by clearing biofilms, inhibiting inflammation activation, restoring periodontal soft hard functions remain very limited. Recent studies highlight link between periodontitis systemic diseases, underscoring complexity disease. There an urgent need find comprehensive treatment plans requirements. Whether integrating new enhance existing treatments or developing approaches replace traditional therapies, efforts will drive advancements in treatment. Therefore, this review compares with treatments. It highlights design concepts mechanisms functional materials, their properties, discusses importance strategies. This aims provide guidance for emerging research promote development precise efficient

Language: Английский

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Harnessing human adipose-derived stromal cell chondrogenesis in vitro for enhanced endochondral ossification

Biomaterials, Journal Year: 2023, Volume and Issue: 303, P. 122387 - 122387

Published: Nov. 6, 2023

Endochondral ossification (ECO), the major process during embryogenesis and bone repair, involves formation of a cartilaginous template remodelled into functional organ. Adipose-derived stromal cells (ASC), non-skeletal multipotent progenitors from vascular fraction (SVF) human adipose tissue, were shown to recapitulate ECO generate organs in vivo when primed hypertrophic cartilage tissue (HCT) vitro. However, reproducibility was limited triggers remain unknown. We studied effect expansion maturation HCT on induction process. SVF or expanded ASC seeded onto collagen sponges, cultured chondrogenic medium for 3–6 weeks implanted ectopically nude mice evaluate their bone-forming capacities. all tested donors formed mature 3 whereas needed 4–5 weeks. A longer increased degree HCT, with gradually denser matrix mineralization. This highly predictive capacity vivo, achieved only an intermediate degree. In parallel, expanding also resulted enrichment characterized by rapid change proteomic profile quiescent proliferative state. Inducing quiescence rescued potential. Our findings emphasize role monolayer provides simple, yet reproducible effective approach be specific clinical models.

Language: Английский

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Batch Effects during Human Bone Marrow Stromal Cell Propagation Prevail Donor Variation and Culture Duration: Impact on Genotype, Phenotype and Function

Cells, Journal Year: 2022, Volume and Issue: 11(6), P. 946 - 946

Published: March 10, 2022

Donor variation is a prominent critical issue limiting the applicability of cell-based therapies. We hypothesized that batch effects during propagation bone marrow stromal cells (BMSCs) in human platelet lysate (hPL), replacing fetal bovine serum (FBS), can affect phenotypic and functional variability. therefore investigated impact donor variation, hPL- vs. FBS-driven exhaustive proliferation, on BMSC epigenome, transcriptome, phenotype, coagulation risk osteochondral regenerative function. Notably, hPL significantly increased created different gene expression trajectories distinct surface marker signatures, already after just one passage. confirmed declining proliferative potential FBS-expanded challenge. Flow cytometry verified canonical fibroblastic phenotype culture-expanded BMSCs. observed limited DNA methylation, preferentially cultures, irrespective culture duration. The clotting over time. Moreover, expansion xenogenic resulted significant loss function 3D cartilage disk formation risk. Superior chondrogenic under hPL-conditions was maintained culture. blood group isoagglutinins had minor These data demonstrate pronounced due to factors, partly outcompeting

Language: Английский

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Enhancer hijacking at the ARHGAP36 locus is associated with connective tissue to bone transformation

Nature Communications, Journal Year: 2023, Volume and Issue: 14(1)

Published: April 11, 2023

Heterotopic ossification is a disorder caused by abnormal mineralization of soft tissues in which signaling pathways such as BMP, TGFβ and WNT are known key players driving ectopic bone formation. Identifying novel genes related to the process important steps for future gene therapy disorders. In this study, we detect an inter-chromosomal insertional duplication female proband disrupting topologically associating domain causing ultra-rare progressive form heterotopic ossification. This structural variant lead enhancer hijacking misexpression ARHGAP36 fibroblasts, validated here orthogonal vitro studies. addition, overexpression inhibits TGFβ, activates hedgehog genes/proteins extracellular matrix production. Our work on genetic cause case has revealed that plays role formation metabolism, outlining first details contributing bone-formation -disease.

Language: Английский

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Characterization of anthracycline-induced cardiotoxicity by diffusion tensor magnetic resonance imaging

Basic Research in Cardiology, Journal Year: 2024, Volume and Issue: unknown

Published: March 14, 2024

Abstract Anthracyclines are highly potent anti-cancer drugs, but their clinical use is limited by severe cardiotoxic side effects. The impact of anthracycline-induced cardiotoxicity (AIC) on left ventricular (LV) microarchitecture and diffusion properties remains unknown. This study sought to characterize AIC cardiovascular magnetic resonance tensor imaging (DTI). Mice were treated with Doxorubicin (DOX; n = 16) for induction or saline as corresponding control ( 15). Cardiac function was assessed via echocardiography at the end period. Whole hearts 8 per group) scanned ex vivo high-resolution DTI 7 T. Results correlated histopathology mass spectrometry imaging. demonstrated systolic dysfunction (LVEF 52 ± 3% vs. 43 6%, P < 0.001), impaired global longitudinal strain (−19.6 2.0% −16.6 3.0%, 0.01), cardiac atrophy (LV index [mg/mm], 4.3 0.1 3.6 0.2, 0.01). Regional sheetlet angles significantly lower in AIC, whereas helix angle relative helicity remained unchanged. In fractional anisotropy increased (0.12 0.01 0.14 0.02, 0.05). DOX-treated mice displayed higher planar less spherical C Planar 0.07 0.09 0.01, 0.01; Spherical 0.89 0.87 yielded good discriminatory power distinguish between without (c-index 0.91 0.84, respectively, both associated regional changes no major abnormalities LV microarchitecture. geometric shape altered AIC. may provide a new tool myocardial characterization patients which warrants future studies evaluate its diagnostic utility.

Language: Английский

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Cellular Scale Curvature in Bioceramic Scaffolds Enhanced Bone Regeneration by Regulating Skeletal Stem Cells and Vascularization

Advanced Healthcare Materials, Journal Year: 2024, Volume and Issue: 13(29)

Published: June 24, 2024

Critical-sized segmental bone defects cannot heal spontaneously, leading to disability and significant increase in mortality. However, current treatments utilizing grafts face a variety of challenges from donor availability poor osseointegration. Drugs such as growth factors cancer risk are very costly. Here, porous bioceramic scaffold that promotes regeneration via solely mechanobiological design is reported. Two types scaffolds with high versus low pore curvatures created using high-precision 3D printing technology fabricate radius the 100s micrometers. While both able support formation, high-curvature pores induce higher ectopic formation increased vessel invasion. Scaffolds also promote faster critical-sized by activating mechanosensitive pathways. High-curvature recruits skeletal stem cells type H vessels periosteum marrow during early phase repair. have survival transplanted GFP-labeled (SSCs) recruit more host SSCs. Taken together, defined micrometer-scale demonstrate approach for orthopedic design.

Language: Английский

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