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1.
Biomaterials ; 308: 122549, 2024 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-38554643

RESUMEN

The availability of human cell-based models capturing molecular processes of cartilage degeneration can facilitate development of disease-modifying therapies for osteoarthritis [1], a currently unmet clinical need. Here, by imposing specific inflammatory challenges upon mesenchymal stromal cells at a defined stage of chondrogenesis, we engineered a human organotypic model which recapitulates main OA pathological traits such as chondrocyte hypertrophy, cartilage matrix mineralization, enhanced catabolism and mechanical stiffening. To exemplify the utility of the model, we exposed the engineered OA cartilage organoids to factors known to attenuate pathological features, including IL-1Ra, and carried out mass spectrometry-based proteomics. We identified that IL-1Ra strongly reduced production of the transcription factor CCAAT/enhancer-binding protein beta [2] and demonstrated that inhibition of the C/EBPß-activating kinases could revert the degradative processes. Human OA cartilage organoids thus represent a relevant tool towards the discovery of new molecular drivers of cartilage degeneration and the assessment of therapeutics targeting associated pathways.


Asunto(s)
Organoides , Osteoartritis , Ingeniería de Tejidos , Humanos , Organoides/metabolismo , Organoides/patología , Osteoartritis/patología , Osteoartritis/metabolismo , Ingeniería de Tejidos/métodos , Células Madre Mesenquimatosas/metabolismo , Células Madre Mesenquimatosas/citología , Condrogénesis , Condrocitos/metabolismo , Condrocitos/patología , Cartílago Articular/patología , Cartílago Articular/metabolismo , Cartílago/patología , Cartílago/metabolismo , Proteína beta Potenciadora de Unión a CCAAT/metabolismo , Proteómica
2.
Biomater Adv ; 141: 213099, 2022 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-36088719

RESUMEN

Skeletal disorders represent a variety of degenerative diseases that affect bone and cartilage homeostasis. The regenerative capacity of bone is affected in osteoporosis, osteoarthritis, rheumatoid arthritis, bone fractures, congenital defects, and bone cancers. There is no viable, non-invasive treatment option and bone regeneration requires surgical intervention with the implantation of bone grafts. Incorporating nanoparticles in bone grafts have improved fracture healing by providing fine structures for bone tissue engineering. It is currently a revolutionary finding in the field of regenerative medicine. Silver nanoparticles (AgNPs) have garnered particular attention due to their well-known anti-microbial and potential osteoinductive properties. In addition, AgNPs have been demonstrated to regulate the proliferation and differentiation of mesenchymal stem cells (MSCs) involved in bone regeneration. Furthermore, AgNPs have shown toxicity towards cancer cells derived from bone. In the last decade, there have been multiple studies focusing on the effect of nanoparticles on the proliferation and/or differentiation of MSCs and bone cancer cells; however, the specific studies with AgNPs are limited. Although the reported investigations show promising in vitro and in vivo potential of AgNPs for application in bone regeneration, more studies are required to ensure their implications in bone tissue engineering. This review aims to highlight the current advances related to the production of AgNPs and their effect on MSCs and bone cancer cells, which will potentiate their possible implications in orthopedics. Moreover, this review article evaluates the future of AgNPs in bone tissue engineering.


Asunto(s)
Células Madre Mesenquimatosas , Nanopartículas del Metal , Huesos , Nanopartículas del Metal/uso terapéutico , Plata/farmacología , Ingeniería de Tejidos
3.
Micron ; 140: 102963, 2021 01.
Artículo en Inglés | MEDLINE | ID: mdl-33130547

RESUMEN

The study employs conventional techniques and quantitative image analysis tools to characterize alginate-capped nanosilver synthesized by green methods. Sodium Alginate (0.5 %, 1 % and 2 %) was used as a reducing and stabilizing agent. Presence of particles was confirmed by UV-vis Spectroscopy, with absorbance maxima of 412-413 nm for 0.5 %, 1 % and 2 % of polymer. Hydrodynamic sizes of particles recorded for 0.5 %, 1 % and 2 % polymer were 128.4 ± 1.5, 129.9 ± 3.6 and 148.6 ± 1.0 nm by DLS. TEM revealed roughly spherical to cuboidal particles ranging from 15-20 nm and clusters of 100 nm and Energy Dispersive X-ray Spectroscopy confirmed the presence of silver in the particles. Analysis of the TEM images was done in MATLAB R2016b using histogram equalisation for image enhancement and entropy filtering for image segmentation. These techniques revealed the surface pores and polymer distribution around the particle. Statistical analysis (ANOVA) was performed for the measured fractal dimensions of nanoparticles with polymer coating, width of particle together with polymer coating, and thickness of only polymer coating around the particle for various study groups. Significant differences (p < 0.05) were found both between and within the study groups for fractal dimensions of nanoparticles with polymer coating, width of nanoparticles and thickness of polymer coating alone. The analysis was successful in confirming presence and thickness of polymer layer on particles.

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