Multilineage differentiation of human mesenchymal stem cells in a three-dimensional nanofibrous scaffold

Li, Wan‐Ju; Tuli, Richard; Huang, Xiaoxue; Laquerrière, Patrice; Tuan, Rocky S.

doi:10.1016/j.biomaterials.2005.01.002

Cited by 586 publications

(401 citation statements)

References 38 publications

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“…Mesenchymal stem cells undergo osteogenic differentiation with the support of nanofibrous scaffolds in vitro and in vivo. 28,29 Human bone marrow stromal cells were found to adhere and proliferate well on a polymeric nanofiber scaffold. The cells were found to crosslink the nanofibers in the matrix and integrate with the surrounding fibers to form a 3D cellular network.…”

Section: Effects Of Exfoliated Carbon Nanofibers In a Rat Femoral Framentioning

confidence: 99%

“…The cells were found to crosslink the nanofibers in the matrix and integrate with the surrounding fibers to form a 3D cellular network. 28 ExCNFs also have a large edge area, which is thought to affect cells and accelerate bone fusion. Additionally, ExCNFs combined with MedGEL accelerate bone fusion to a greater degree in response to BMP.…”

Section: Effects Of Exfoliated Carbon Nanofibers In a Rat Femoral Framentioning

confidence: 99%

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Enhancement of the Effects of Exfoliated Carbon Nanofibers by Bone Morphogenetic Protein in a Rat Femoral Fracture Model

Miyazaki

Toyoda

Yoshiiwa

et al. 2014

Journal Orthopaedic Research

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Exfoliated carbon nanofibers (ExCNFs) are expected to serve as excellent scaffolds for promoting and guiding bone-tissue regeneration. We aimed to enhance the effects of ExCNFs with bone morphogenetic proteins (BMPs) and examine their feasibility and safety in clinical applications using a rat femoral fracture model. Group I (n ¼ 16) animals were implanted with control MedGEL. Group II (n ¼ 17) animals were implanted with MedGEL containing ExCNFs. Group III (n ¼ 15) animals were implanted with MedGEL containing 1 mg rhBMP-2. Group IV (n ¼ 15) animals were implanted with MedGEL containing 1 mg rhBMP-2 and ExCNFs. The rats were euthanized after 6 weeks, and their fractured femurs were explanted and assessed by manual palpation, radiographs, and highresolution microcomputerized tomography (micro-CT); the femurs were also subjected to biomechanical and histological analysis. The fusion rates in Group IV (73.3%) were considerably higher than those in Groups I (25. Keywords: exfoliated carbon nanofiber; bone morphogenetic protein; fracture healing; rat femoral fracture model; scaffold Bone morphogenetic proteins (BMPs) are members of the transforming growth factor b superfamily and are powerful osteoinductive molecules. The osteoinductive effects of recombinant human BMPs (rhBMPs) in surgical procedures such as fracture repair, healing of critical-size bone defects, and spinal fusion have been demonstrated in animal models and clinical trials; furthermore, rhBMP-2 and rhBMP-7 have been approved for clinical use. [1][2][3][4][5] Unfortunately, the results of clinical trials show that high doses of BMPs are required to induce adequate bone fusion, as the molecules are soluble and easily diffuse away from the fusion site, becoming inactivated in vivo. 6 In addition, the usefulness of BMPs is limited by their high costs. To address these problems, a number of strategies are being developed to generate safer, less expensive, and more efficacious spinal fusion using rhBMP. However, the efficient immobilization of BMPs onto carriers at low dosage while maintaining desirable in vivo regenerative action remains as a major challenge in bone regeneration research and practice. 7,8 The required rhBMP-2 level in humans, even for the FDA-approved collagen sponge-incorporated treatment, is much higher (over six orders of magnitude greater) than that used for in vitro cell level evaluation and in vivo animal studies. 7,9 Several ongoing investigations aim to develop a scaffold that functions as a delivery vehicle, providing cells with a more controlled and sustained release of bioactive molecules to maintain the local growth factor concentration within the therapeutic range.Carbon nanotubes (CNTs) have received much attention because of their interesting properties, including their exceptional mechanical 10 and high electrical and thermal conductivity, 11 which facilitate their use as reinforcements or additives in materials such as plastics, metals, and ceramics to improve the properties of the materials and introduce nove...

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Section: Effects Of Exfoliated Carbon Nanofibers In a Rat Femoral Framentioning

confidence: 99%

Section: Effects Of Exfoliated Carbon Nanofibers In a Rat Femoral Framentioning

confidence: 99%

Enhancement of the Effects of Exfoliated Carbon Nanofibers by Bone Morphogenetic Protein in a Rat Femoral Fracture Model

Miyazaki

Toyoda

Yoshiiwa

et al. 2014

Journal Orthopaedic Research

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“…These fibers are exceedingly long (km range) compared with their diameters (x), which usually follow a unimodal statistical distribution. The mean and spread of such distributions can be controlled and tweaked via process parameters over a wide range, from a few nanometers to hundreds of microns [10][11][12][13][14][15][16][17][18][19][20][21][22][23]. The fiber diameter x is regarded as the prime controllable design parameter to steer scaffold performance in terms of cell response.…”

Section: Introductionmentioning

confidence: 99%

“…Reportedly, nanoscale fibers, in the absence of beads, were found to accelerate and improve cell adhesion and proliferation in the presence of growth factors with respect to the microscale counterpart -partly owing to the higher specific surface area providing a kinetic boost [18,21]. Nanofibers also appeared to sustain growth factor-induced stem cell differentiation [14,15,17,22,23]. However, dense nanoscale networks are not optimal, as they tend to block cell migration through the thickness and are outperformed by microscale fibers in terms of cell ingrowth and viability [20].…”

Section: Introductionmentioning

confidence: 99%

“…However, dense nanoscale networks are not optimal, as they tend to block cell migration through the thickness and are outperformed by microscale fibers in terms of cell ingrowth and viability [20]. In fact, after homogeneous cell delivery onto the surface (for seeding details see [2,22,24,25]) only the presence of interconnected pores, large enough compared with the dimension of seeded cells, renders the substrate permeable to cells and permits tissue formation [26].…”

Section: Introductionmentioning

confidence: 99%

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Multiscale three-dimensional scaffolds for soft tissue engineering via multimodal electrospinning

et al. 2010

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a b s t r a c tA novel (scalable) electrospinning process was developed to fabricate bio-inspired multiscale threedimensional scaffolds endowed with a controlled multimodal distribution of fiber diameters and geared towards soft tissue engineering. The resulting materials finely mingle nano-and microscale fibers together, rather than simply juxtaposing them, as is commonly found in the literature. A detailed proof of concept study was conducted on a simpler bimodal poly(e-caprolactone) (PCL) scaffold with modes of fiber distribution at 600 nm and 3.3 lm. Three conventional unimodal scaffolds with mean diameters of 300 nm and 2.6 and 5.2 lm, respectively, were used as controls to evaluate the new materials. Characterization of the microstructure (i.e. porosity, fiber distribution and pore structure) and mechanical properties (i.e. stiffness, strength and failure mode) indicated that the multimodal scaffold had superior mechanical properties (Young's modulus $40 MPa and strength $1 MPa) in comparison with the controls, despite the large porosity ($90% on average). A biological assessment was conducted with bone marrow stromal cell type (mesenchymal stem cells, mTERT-MSCs). While the new material compared favorably with the controls with respect to cell viability (on the outer surface), it outperformed them in terms of cell colonization within the scaffold. The latter result, which could neither be practically achieved in the controls nor expected based on current models of pore size distribution, demonstrated the greater openness of the pore structure of the bimodal material, which remarkably did not come at the expense of its mechanical properties. Furthermore, nanofibers were seen to form a nanoweb bridging across neighboring microfibers, which boosted cell motility and survival. Lastly, standard adipogenic and osteogenic differentiation tests served to demonstrate that the new scaffold did not hinder the multilineage potential of stem cells.

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Electrospinning

2007

Encyclopedia of Polymer Science and Technology

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Electrostatic fiber spinning or “electrospinning,” employs electrostatic forces to eject a charged fluid jet from a nozzle to make a fiber. Generally, the fiber is laid down on a collector to form a nonwoven mat. Electrospinning is also directly related to a well‐established process called electrospraying, in which tiny droplets are obtained instead of fibers. Almost any material that can be spun from melt or solution by conventional methods can be electrospun into fibers. This article details the electrospinning process. Theoretical background information is also supplied. Electrospinning devices come in different shapes and sizes and these are described. The dynamics of electrospinning are complex. A general guide to the effects of fiber properties and processing parameters on fiber diameter is given. Electrospun products include tissue scaffolds, inorganic nanofibers for catalysis, carbon nanofibers, composite fibers, and mats.

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Multilineage differentiation of human mesenchymal stem cells in a three-dimensional nanofibrous scaffold

Cited by 586 publications

References 38 publications

Enhancement of the Effects of Exfoliated Carbon Nanofibers by Bone Morphogenetic Protein in a Rat Femoral Fracture Model

Enhancement of the Effects of Exfoliated Carbon Nanofibers by Bone Morphogenetic Protein in a Rat Femoral Fracture Model

Multiscale three-dimensional scaffolds for soft tissue engineering via multimodal electrospinning

Electrospinning

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