Bioinstructive Naringin‐Loaded Micelles for Guiding Stem Cell Osteodifferentiation

Lavrador, Pedro; Gaspar, Vítor M.; Mano, João F.

doi:10.1002/adhm.201800890

Cited by 20 publications

(19 citation statements)

References 50 publications

(62 reference statements)

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“…28 The application of naringin-loaded polymeric micelles to human adipose-derived stem cells yielded greater osteogenic differentiation, as characterized by increased osteopontin expression and bony matrix mineralization, than was observed in the presence of free naringin. 29 Naringin additionally enhances osteoblast survival by increasing 1α,25dihydroxyvitamin D 3 signaling in osteoblasts in vitro. 30 The pro-osteogenic effects of naringin may also be linked to its ability to downregulate peroxisome proliferator-activated receptor (PPAR)γ (a key regulator of adipogenesis) expression in BMSCs, as well as its activation of the neurogenic locus Notch homolog protein (Notch) signaling pathway 31,32 [ Figure 1(b)].…”

Section: Differentiation Of Bone Resident Cells and Osteogenesismentioning

confidence: 99%

Re-appraising the potential of naringin for natural, novel orthopedic biotherapies

Alder

Morris

et al. 2020

Therapeutic Advances in Musculoskeletal

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Naringin is a naturally occurring flavonoid found in plants of the Citrus genus that has historically been used in traditional Chinese medical regimens for the treatment of osteoporosis. Naringin modulates signaling through numerous molecular pathways critical to musculoskeletal development, cellular differentiation, and inflammation. Administration of naringin increases in vitro expression of bone morphogenetic proteins (BMPs) and activation of the Wnt/β-catenin and extracellular signal-related kinase (Erk) pathways, thereby promoting osteoblastic proliferation and differentiation from stem cell precursors for bone formation. Naringin also inhibits osteoclastogenesis by both modifying RANK/RANKL interactions and inducing apoptosis in osteoclasts in vitro. In addition, naringin acts on the estrogen receptor in bone to mimic the native bone-preserving effects of estrogen, with few systemic side effects on other estrogen-sensitive tissues. The efficacy of naringin therapy in reducing the osteolysis characteristic of common musculoskeletal pathologies such as osteoporosis, degenerative joint disease, and osteomyelitis, as well as inflammatory conditions affecting bone such as diabetes mellitus, has been extensively demonstrated in vitro and in animal models. Naringin thus represents a naturally abundant, cost-efficient agent whose potential for use in novel musculoskeletal biotherapies warrants re-visiting and further exploration through human studies. Here, we review the cellular mechanisms of action that have been elucidated regarding the action of naringin on bone resident cells and the bone microenvironment, in vivo evidence of naringin’s osteostimulative and chondroprotective properties in the setting of osteolytic bone disease, and current limitations in the development of naringin-containing translational therapies for common musculoskeletal conditions.

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Section: Differentiation Of Bone Resident Cells and Osteogenesismentioning

confidence: 99%

Re-appraising the potential of naringin for natural, novel orthopedic biotherapies

Alder

Morris

et al. 2020

Therapeutic Advances in Musculoskeletal

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“…[ 9,10 ] On the other hand, nanoparticles are uniquely suited for serving as efficient bioactive molecule reservoirs of hydrophilic and hydrophobic compounds. [ 11,12 ] Nanoparticles can generally be divided in two major classes: i) organic nanoparticles (i.e., polymeric, lipidic and/or proteins) and ii) inorganic nanoparticles (i.e., silicates, metal ions, rare earth elements, etc.). [ 13,14 ] Organic nanoparticles are typically soft, exhibit high biomolecule loading capacity and are easily programmable due to their chemical versatility, allowing the incorporation of a wide array of stimuli‐responsive features in their backbone.…”

Section: Introductionmentioning

confidence: 99%

Stimuli‐Responsive Nanocomposite Hydrogels for Biomedical Applications

Lavrador

Esteves

Gaspar

et al. 2020

Adv Funct Materials

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308

201

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The complex tissue‐specific physiology that is orchestrated from the nano‐ to the macroscale, in conjugation with the dynamic biophysical/biochemical stimuli underlying biological processes, has inspired the design of sophisticated hydrogels and nanoparticle systems exhibiting stimuli‐responsive features. Recently, hydrogels and nanoparticles have been combined in advanced nanocomposite hybrid platforms expanding their range of biomedical applications. The ease and flexibility of attaining modular nanocomposite hydrogel constructs by selecting different classes of nanomaterials/hydrogels, or tuning nanoparticle‐hydrogel physicochemical interactions widely expands the range of attainable properties to levels beyond those of traditional platforms. This review showcases the intrinsic ability of hybrid constructs to react to external or internal/physiological stimuli in the scope of developing sophisticated and intelligent systems with application‐oriented features. Moreover, nanoparticle‐hydrogel platforms are overviewed in the context of encoding stimuli‐responsive cascades that recapitulate signaling interplays present in native biosystems. Collectively, recent breakthroughs in the design of stimuli‐responsive nanocomposite hydrogels improve their potential for operating as advanced systems in different biomedical applications that benefit from tailored single or multi‐responsiveness.

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“…Interestingly, bioactive colloidal gels placed in direct contact with activated macrophages consistently led to the lowest nitrite concentration and highest arginase activity, thus eliciting a more pronounced dampening of the proinflammatory response to LPS stimuli. The improved bioinstructiveness of colloidal gel platforms over free drug treatments can be assigned to enhanced flavonoid bioactivity through encapsulation and cellular internalization, as previously established for nanoparticle systems. − …”

Section: Results and Discussionmentioning

confidence: 97%

Self-Assembled Bioactive Colloidal Gels as Injectable Multiparticle Shedding Platforms

Freitas

Lavrador

Almeida

et al. 2020

ACS Appl. Mater. Interfaces

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Self-assembled colloidal gels are highly versatile 3D nanocluster platforms with potential to overcome the rapid clearing issues associated with standard free nanotherapeutics administration. However, the development of nanoassembled colloidal gels exhibiting autonomous multiparticle release from the bulk particle network remains elusive. Herein, we generated multiparticle colloidal gels from two nanosized building blocks: cationic poly(d,l-lactide-co-glycolide)–polyethylenimine (PLGA–PEI) nanoparticles and anionic zein–hyaluronan (HA) nanogels that assemble into macrosized 3D constructs via attractive electrostatic forces. The resulting colloidal gels exhibited high stability in complex culture medium as well as fit-to-shape moldable properties and injectability. Moreover, nanoassembled colloidal gels encapsulated bioactive quercetin flavonoids with high loading efficacy and presented remarkable anti-inflammatory activities, reducing key proinflammatory biomarkers in inflammation-activated macrophages. More importantly, because of their rationally selected building blocks zein−HA/PLGA−PEI, self-assembled colloidal platforms displayed autonomous multiparticle shedding. Both positive and negative particles released from the colloidal system were efficiently internalized by macrophages along time as evidenced by quantitative particle uptake analysis. Overall, the generated nanostructured gels represent an implantable versatile platform for focalized multiparticle delivery. In addition, the possibility to combine a higher number of particle species with different properties or stimuli-responsiveness enables the manufacturing of combinatorial nanostructured gels for numerous biomedical applications.

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Bioinstructive Naringin‐Loaded Micelles for Guiding Stem Cell Osteodifferentiation

Cited by 20 publications

References 50 publications

Re-appraising the potential of naringin for natural, novel orthopedic biotherapies

Re-appraising the potential of naringin for natural, novel orthopedic biotherapies

Stimuli‐Responsive Nanocomposite Hydrogels for Biomedical Applications

Self-Assembled Bioactive Colloidal Gels as Injectable Multiparticle Shedding Platforms

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