Combinational effect of matrix elasticity and alendronate density on differentiation of rat mesenchymal stem cells

Jiang, Peipei; Mao, Zhengwei; Gao, Changyou

doi:10.1016/j.actbio.2015.03.018

Cited by 56 publications

(36 citation statements)

References 59 publications

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“…It has previously been reported that GelMA and PEG induced ECM calcification. [46][47][48][49][50][51][52] For example, Turkkan et al 53 showed that electrospun PCL:PEG with hydroxyapatite induced in vitro osteoblast mineralization. Tiwari et al 18 electrospun different combinations of PCL and PEG and evaluated their potential to induce in vitro mineralization.…”

Section: Resultsmentioning

confidence: 99%

Electrospun nanofiber blend with improved mechanical and biological performance

Lobo

Afewerki

Paula

et al. 2018

IJN

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BackgroundHere, electrospun fibers based on a blend of polycaprolactone (PCL), poly(ethylene glycol) (PEG), and gelatin methacryloyl (GelMA) were developed. The careful choice of this polymer combination allowed for the preparation of a biomaterial that preserved the mechanical strength of PCL, while at the same time improving the hydrophilicity of the blended material and human osteoblast maturation.MethodsThe morphology, chemical structure, wettability, and mechanical properties before and after UV photocrosslinking were evaluated. Furthermore, human osteoblasts (hFOB) were cultivated for up to 21 days on the scaffolds, and their potential to upregulate cell proliferation, alkaline phosphatase (ALP) activity, and calcium deposition were investigated.ResultsContact angle measurement results showed that the developed scaffolds presented hydrophilic properties after PEG and GelMA incorporation before (25°) and after UV photocross-linking (69°) compared to pure PCL (149°). PCL:PEG:GelMA-UV displayed a slight increase in mechanical strength (elastic modulus ~37 MPa) over PCL alone (~33 MPa). Normally, an increase in strength of fibers leads to a decrease in elongation at break, due to the material becoming less deformable and stiffer, thus leading to breaks at low strain. This behavior was observed by comparing PCL (elongation at break ~106%) and PCL:PEG:GelMA-UV (~50%). Moreover, increases in ALP activity (10-fold at day 14) and calcium deposition (1.3-fold at day 21) by hFOBs were detected after PEG and GelMA incorporation after UV photocross-linking compared to pure PCL. Ultrathin and hydrophilic fibers were obtained after PEG and GelMA incorporation after UV photocrosslinking, but the strength of PCL was maintained. Interestingly, those ultrathin fiber characteristics improved hFOB functions.ConclusionThese findings appear promising for the use of these electrospun scaffolds, based on the combination of polymers used here for numerous orthopedic applications.

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Section: Resultsmentioning

confidence: 99%

Electrospun nanofiber blend with improved mechanical and biological performance

Lobo

Afewerki

Paula

et al. 2018

IJN

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“…MSC responses to variations in ECM stiffness have been studied previously in mice [ 8 , 34 ], rats [ 35 ], and humans [ 36 , 37 ]. The present study examined this phenomenon in hMSCs to provide an accurate theoretical basis for clinical treatment.…”

Section: Discussionmentioning

confidence: 99%

Extracellular matrix stiffness controls osteogenic differentiation of mesenchymal stem cells mediated by integrin α5

et al. 2018

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BackgroundHuman mesenchymal stem cell (hMSC) differentiation into osteoblasts has important clinical significance in treating bone injury, and the stiffness of the extracellular matrix (ECM) has been shown to be an important regulatory factor for hMSC differentiation. The aim of this study was to further delineate how matrix stiffness affects intracellular signaling through integrin α5/β1, FAK, and Wnt signaling, subsequently regulating the osteogenic phenotype of hMSCs.MethodshMSCs were cultured on tunable polyacrylamide hydrogels coated with fibronectin with stiffness corresponding to a Young’s modulus of 13–16 kPa and 62–68 kPa. After hMSCs were cultured on gels for 1 week, gene expression of alpha-1 type I collagen, BGLAP, and RUNX2 were evaluated by real-time PCR. After hMSCs were cultured on gels for 24 h, signaling molecules relating to integrin α5 (FAK, ERK, p-ERK, Akt, p-Akt, GSK-3β, p-GSK-3β, and β-catenin) were evaluated by western blot analysis.ResultsOsteogenic differentiation was increased on 62–68 kPa ECM, as evidenced by alpha-1 type I collagen, BGLAP, and RUNX2 gene expression, calcium deposition, and ALP staining. In the process of differentiation, gene and protein expression of integrin α5/β1 increased, together with protein expression of the downstream signaling molecules FAK, p-ERK, p-Akt, GSK-3β, p-GSK-3β, and β-catenin, indicating that these molecules can affect the osteogenic differentiation of hMSCs. An antibody blocking integrin α5 suppressed the stiffness-induced expression of all osteoblast markers examined. In particular, alpha-1 type I collagen, RUNX2, and BGLAP were significantly downregulated, indicating that integrin α5 regulates hMSC osteogenic differentiation. Downstream expression of FAK, ERK, p-ERK, and β-catenin protein was unchanged, whereas Akt, p-Akt, GSK-3β, and p-GSK-3β were upregulated. Moreover, expression of Akt and p-Akt was upregulated with anti-integrin α5 antibody, but no difference was observed for FAK, ERK, and p-ERK between the with or without anti-integrin α5 antibody groups. At the same time, expression of GSK-3β and p-GSK-3β was upregulated and β-catenin levels showed no difference between the groups with or without anti-integrin α5 antibody. Since Akt, p-Akt, GSK-3β, and p-GSK-3β displayed the same changes between the groups with or without anti-integrin α5 antibody, we then detected the links among them. Expression of p-Akt and p-GSK-3β was reduced effectively in the presence of the Akt inhibitor Triciribine. However, Akt, GSK-3β, and β-catenin were unchanged. These results suggested that expression of p-GSK-3β was regulated by p-Akt on 62–68 kPa ECM.ConclusionsTaken together, our results provide evidence that matrix stiffness (62–68 kPa) affects the osteogenic outcome of hMSCs through mechanotransduction events that are mediated by integrin α5.Electronic supplementary materialThe online version of this article (10.1186/s13287-018-0798-0) contains supplementary material, which is available to authorized users.

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“…Interestingly, the results demonstrate that not only the osteogenesis related genes (ALP, BMP2, OCN, OPG) are upregulated, but also the key factor for osteoclastogenesis is remarkably down-regulated by 10 À8 M AL ( Figure 6). Numerous studies have confirmed that proper concentrations of AL could stimulate the proliferation and differentiation of BMSCs and osteoblasts derived from non-osteoporotic models [10,36,37]. But very few studies were reported on the influence of AL on BMSCs derived from the osteoporotic models, especially focusing on the RANKL and OPG expressions of BMSCs-OVX.…”

Section: Discussionmentioning

confidence: 99%

Alendronate delivery on amino modified mesoporous bioactive glass scaffolds to enhance bone regeneration in osteoporosis rats

Wang¹,

Zeng²,

Weng

et al. 2018

Artificial Cells, Nanomedicine, and Biotechnology

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The regeneration capacity of osteoporotic bones is generally lower than that of normal bones. Nowadays, alendronate (AL) are orally administrated for osteoporosis due to the inhibition of bone resorption. However, systemic administration of AL is characterized by extremely low bioavailability and high toxicity. In this study, the amino-modified mesoporous bioactive glass scaffolds (N-MBGS) were fabricated by a simple powder processing technique as a novel drug-delivery system for AL. The effects of AL on the osteogenic differentiation of bone mesenchymal stem cells derived from ovariectomized rats (rBMSCs-OVX) were first estimated. The loading efficiency and release kinetics of AL on N-MBGS were investigated in vitro and the osteogenesis of AL-loaded N-MBGS in rat calvarial defect model was detected by micro-CT measurements and the histological assay. Our results revealed that proper concentration of AL significantly promoted osteogenic differentiation of rBMSCs-OVX. The amount and delivery rate of AL were greatly improved through amino modification. Additionally, scaffolds with AL showed better bone formation in vivo, especially for the N-MBGS group. Our results suggest that the novel amino-modified MBGS are promising drug-delivery system for osteoporotic bone defect repairing or regeneration. The experimental schematic of the novel amino-modified MBGS as a promising drug-delivery system for osteoporotic bone regeneration.

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Combinational effect of matrix elasticity and alendronate density on differentiation of rat mesenchymal stem cells

Cited by 56 publications

References 59 publications

Electrospun nanofiber blend with improved mechanical and biological performance

Electrospun nanofiber blend with improved mechanical and biological performance

Extracellular matrix stiffness controls osteogenic differentiation of mesenchymal stem cells mediated by integrin α5

Alendronate delivery on amino modified mesoporous bioactive glass scaffolds to enhance bone regeneration in osteoporosis rats

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