The osteogenic differentiation of rat bone marrow stromal cells cultured with dexamethasone-loaded carboxymethylchitosan/poly(amidoamine) dendrimer nanoparticles

Oliveira, Joaquím M.; Sousa, Rui A.; Kotobuki, Noriko; Tadokoro, Mika; Hirose, Motohiro; Mano, João F.; Reis, Rui L.; Ohgushi, Hajime

doi:10.1016/j.biomaterials.2008.10.024

Cited by 130 publications

(105 citation statements)

References 47 publications

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“…The increase in DNA content in BM indicated that hMSCs were able to grow in the encapsulating PEGDA matrix but DNA content decreased with incubation time as the encapsulated cells underwent differentiation in OM consistent with previous reports. 52,53 Addition of BMP-2 peptide, peptide hydrophobicity, or peptide conjugation to the PEGDA matrix did not have a significant effect on cell number with incubation time.…”

Section: Resultsmentioning

confidence: 99%

Experimental and Computational Investigation of the Effect of Hydrophobicity on Aggregation and Osteoinductive Potential of BMP-2-Derived Peptide in a Hydrogel Matrix

Moeinzadeh

Barati²,

Sarvestani³

et al. 2015

Tissue Engineering Part A

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An attractive approach to reduce the undesired side effects of bone morphogenetic proteins (BMPs) in regenerative medicine is to use osteoinductive peptide sequences derived from BMPs. Although the structure and function of BMPs have been studied extensively, there is limited data on structure and activity of BMP-derived peptides immobilized in hydrogels. The objective of this work was to investigate the effect of concentration and hydrophobicity of the BMP-2 peptide, corresponding to residues 73-92 of the knuckle epitope of BMP-2 protein, on peptide aggregation and osteogenic differentiation of human mesenchymal stem cells encapsulated in a polyethylene glycol (PEG) hydrogel. The peptide hydrophobicity was varied by capping PEG chain ends with short lactide segments. The BMP-2 peptide with a positive index of hydrophobicity had a critical micelle concentration (CMC) and formed aggregates in aqueous solution. Based on simulation results, there was a slight increase in the concentration of free peptide in solution with 1000-fold increase in peptide concentration. The dose-osteogenic response curve of the BMP-2 peptide was in the 0.0005-0.005 mM range, and osteoinductive potential of the BMP-2 peptide was significantly less than that of BMP-2 protein even at 1000-fold higher concentrations, which was attributed to peptide aggregation. Further, the peptide or PEG-peptide aggregates had significantly higher interaction energy with the cell membrane compared with the free peptide, which led to a higher nonspecific interaction with the cell membrane and loss of osteoinductive potential. Conjugation of the BMP-2 peptide to PEG increased CMC and osteoinductive potential of the peptide whereas conjugation to lactide-capped PEG reduced CMC and osteoinductive potential of the peptide. Experimental and simulation results revealed that osteoinductive potential of the BMP-2 peptide is correlated with its CMC and the free peptide concentration in aqueous medium and not the total concentration.

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Section: Resultsmentioning

confidence: 99%

Experimental and Computational Investigation of the Effect of Hydrophobicity on Aggregation and Osteoinductive Potential of BMP-2-Derived Peptide in a Hydrogel Matrix

Moeinzadeh

Barati²,

Sarvestani³

et al. 2015

Tissue Engineering Part A

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“…[16][17][18] Our group, as an example, successfully exploited barium titanate NPs (BTNPs; Figure 1A) as a possible agent for the improvement of osteogenic differentiation of MSCs. 19 BTNPs belong to a class of ferroelectric materials showing high piezoelectricity, 20 and with regard to biomedical applications, they demonstrate high cytocompatibility, 21 excellent properties as nonlinear imaging probes, 22 and the ability to deliver doxorubicin in cancer cells by improving Notes: scanning electron microscopy image of BTNPs (A).…”

mentioning

confidence: 99%

Barium titanate nanoparticles and hypergravity stimulation improve differentiation of mesenchymal stem cells into osteoblasts

Rocca¹,

Marino²,

Rocca³

et al. 2015

IJN

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Background Enhancement of the osteogenic potential of mesenchymal stem cells (MSCs) is highly desirable in the field of bone regeneration. This paper proposes a new approach for the improvement of osteogenesis combining hypergravity with osteoinductive nanoparticles (NPs). Materials and methods In this study, we aimed to investigate the combined effects of hypergravity and barium titanate NPs (BTNPs) on the osteogenic differentiation of rat MSCs, and the hypergravity effects on NP internalization. To obtain the hypergravity condition, we used a large-diameter centrifuge in the presence of a BTNP-doped culture medium. We analyzed cell morphology and NP internalization with immunofluorescent staining and coherent anti-Stokes Raman scattering, respectively. Moreover, cell differentiation was evaluated both at the gene level with quantitative real-time reverse-transcription polymerase chain reaction and at the protein level with Western blotting. Results Following a 20 g treatment, we found alterations in cytoskeleton conformation, cellular shape and morphology, as well as a significant increment of expression of osteoblastic markers both at the gene and protein levels, jointly pointing to a substantial increment of NP uptake. Taken together, our findings suggest a synergistic effect of hypergravity and BTNPs in the enhancement of the osteogenic differentiation of MSCs. Conclusion The obtained results could become useful in the design of new approaches in bone-tissue engineering, as well as for in vitro drug-delivery strategies where an increment of nanocarrier internalization could result in a higher drug uptake by cell and/or tissue constructs.

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“…9,10 The following paragraph focuses on the use of nanoparticles as an effective protein or drug delivery system to support bone tissue regeneration. For this purpose, several nondegradable particles, such as silica, lipid, dendrimer, hydroxyapatite, or gold nanoparticles, [43][44][45][46][47][48][49][50] as well as degradable particles made of poly(L-lactide) 51,52 or poly(L-lactideco-glycolide) (PLGA), 11,42,[52][53][54][55][56] have been used. Frequently, nanoparticles were combined with scaffolds such as proteinaceous hydrogels or degradable polymeric matrixes to facilitate application in bone.…”

Section: Drug Deliverymentioning

confidence: 99%

“…Frequently, nanoparticles were combined with scaffolds such as proteinaceous hydrogels or degradable polymeric matrixes to facilitate application in bone. 47,48,53,55,56 As bone contains bone-forming cells, the osteoblasts, and bone-resorbing cells, the osteoclasts, which act in concert to guarantee bone homeostasis, 57,58 different strategies can be envisioned that could promote the regeneration of bone tissue. On the one hand, osteoblasts could be supported by nanoparticle-based growth factor delivery.…”

Section: Drug Deliverymentioning

confidence: 99%

“…63 Accordingly, dexamethasoneloaded dendrimer nanoparticles in a scaffold supported the osteogenic differentiation of rat MSCs in vitro, like free dexamethasone. 48 However, due to possible unwanted side effects of the drug itself in vivo, such as secondary osteoporosis, 64 a clinical application appears questionable. In addition to the manipulation of osteoblast behavior, the aforementioned second strategy of drug-loaded nanoparticle application in bone regeneration to inhibit osteoclast resorption activity has also been pursued.…”

Section: Drug Deliverymentioning

confidence: 99%

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Nanoparticles and their potential for application in bone

Tautzenberger¹,

Kovtun²,

Ignatius³

2012

IJN

162

137

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Abstract:Biomaterials are commonly applied in regenerative therapy and tissue engineering in bone, and have been substantially refined in recent years. Thereby, research approaches focus more and more on nanoparticles, which have great potential for a variety of applications. Generally, nanoparticles interact distinctively with bone cells and tissue, depending on their composition, size, and shape. Therefore, detailed analyses of nanoparticle effects on cellular functions have been performed to select the most suitable candidates for supporting bone regeneration. This review will highlight potential nanoparticle applications in bone, focusing on cell labeling as well as drug and gene delivery. Labeling, eg, of mesenchymal stem cells, which display exceptional regenerative potential, makes monitoring and evaluation of cell therapy approaches possible. By including bioactive molecules in nanoparticles, locally and temporally controlled support of tissue regeneration is feasible, eg, to directly influence osteoblast differentiation or excessive osteoclast behavior. In addition, the delivery of genetic material with nanoparticulate carriers offers the possibility of overcoming certain disadvantages of standard protein delivery approaches, such as aggregation in the bloodstream during systemic therapy. Moreover, nanoparticles are already clinically applied in cancer treatment. Thus, corresponding efforts could lead to new therapeutic strategies to improve bone regeneration or to treat bone disorders.

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The osteogenic differentiation of rat bone marrow stromal cells cultured with dexamethasone-loaded carboxymethylchitosan/poly(amidoamine) dendrimer nanoparticles

Cited by 130 publications

References 47 publications

Experimental and Computational Investigation of the Effect of Hydrophobicity on Aggregation and Osteoinductive Potential of BMP-2-Derived Peptide in a Hydrogel Matrix

Experimental and Computational Investigation of the Effect of Hydrophobicity on Aggregation and Osteoinductive Potential of BMP-2-Derived Peptide in a Hydrogel Matrix

Barium titanate nanoparticles and hypergravity stimulation improve differentiation of mesenchymal stem cells into osteoblasts

Nanoparticles and their potential for application in bone

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