Influence of nanofibers on the growth and osteogenic differentiation of stem cells: a comparison of biological collagen nanofibers and synthetic PLLA fibers

Schofer, Markus D.; Boudriot, Ulrich; Wack, Christina; Leifeld, Irini; Gräbedünkel, Christian; Dersch, Roland; Rudisile, Markus; Wendorff, Joachim H.; Greiner, Andreas; Paletta, Jürgen R. J.; Fuchs-Winkelmann, Susanne

doi:10.1007/s10856-008-3634-8

Cited by 40 publications

(67 citation statements)

References 26 publications

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“…If at all, PLLA nanofibers tend to result in a down-regulation in BMP-2 expression during the early phase of cultivation. This is supported by a down-regulation of genes associated with osteoblast differentiation as described earlier [19,20]. One explanation might be that, at least in part, an endocrine mechanism could be involved in the development of osteoblasts.…”

Section: Discussionmentioning

confidence: 53%

“…The preparation of PLLA nanofibers and the incorporation of BMP-2 into the nanofibers, as well as their characterization by scanning electron microscopy (SEM) and analysis of static contact angles of water, has been reported earlier [17,18,19,20].…”

Section: Construction Of Nanofibers and Characterizationmentioning

confidence: 99%

“…Extraction of RNA, synthesis of cDNA, as well as quantitative polymerase chain reaction (qPCR) analysis were performed as described earlier [17,18,19,20]. Primers (purchased at TIB Biomol, Berlin, Germany), cycle temperatures, and incubation times for VEGF [23], BMP-2, and 18s rRNA [24,25,26] were previously detailed.…”

Section: Gene Expression Analysismentioning

confidence: 99%

“…MSCs were isolated and cultured according to the preparation of Pittenger et al [21], with minor modifications as mentioned by Brendel et al [22]. Each experiment was carried out four times, as described earlier [17,18,19,20]. …”

mentioning

confidence: 99%

“…These constructs are appropriate as a matrix for osteoblast growth as well as for the osteogenic differentiation of hMSCs in principle [7,8,9]. However, there was a timedependent down-regulation of genes, such as alkaline phosphatase, osteocalcin, and collagen-I, associated with the osteoblast lineage [19,20], indicating that the presence of PLLA nanofibers might influence the gene expression of other genes. If the expression of growth factors is affected, this might have an impact on implant healing.…”

mentioning

confidence: 99%

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Lack of Obvious Influence of PLLA Nanofibers on the Gene Expression of BMP-2 and VEGF during Growth and Differentiation of Human Mesenchymal Stem Cells

Schofer

Fuchs-Winkelmann²,

Wack³

et al. 2009

The Scientific World JOURNAL

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Growth factors like bone morphogenetic protein 2 (BMP-2) and vascular endothelial growth factor (VEGF) play an important role in bone remodeling and fracture repair. Therefore, with respect to tissue engineering, an artificial graft should have no negative impact on the expression of these factors. In this context, the aim of this study was to analyze the impact of poly(L-lactic acid) (PLLA) nanofibers on VEGF and BMP-2 gene expression during the time course of human mesenchymal stem cell (hMSC) differentiation towards osteoblasts. PLLA matrices were seeded with hMSCs and cultivated over a period of 22 days under growth and osteoinductive conditions, and analyzed during the course of culture, with respect to gene expression of VEGF and BMP-2. Furthermore, BMP-2-enwoven PLLA nanofibers were used in order to elucidate whether initial down-regulation of growth factor expression could be compensated. Although there was a great interpatient variability with respect to the expression of VEGF and BMP-2, PLLA nanofibers tend to result in a down-regulation in BMP-2 expression during the early phase of cultivation. This effect was diminished in the case of VEGF gene expression. The initial down-regulation was overcome when BMP-2 was directly incorporated into the PLLA nanofibers by electrospinning. Furthermore, the incorporation of BMP-2 into the PLLA nanofibers resulted in an increase in VEGF gene expression. Summarized, the results indicate that the PLLA nanofibers have little effect on growth factor production. An enhancement in gene expression of BMP-2 and VEGF can be achieved by an incorporation of BMP-2 into the PLLA nanofibers.KEYWORDS: nanofibers, tissue engineering, human mesenchymal stem cells, PLLA, BMP, VEGF Schofer et al.: Growth Factor Gene Expession in hMSCs TheScientificWorldJOURNAL (2009) 9, 313-319 314 INTRODUCTIONThe reconstruction of large bony defects after injury or tumor resection often requires the use of graft material. Besides autologous bone grafts, artificial scaffolds based on synthetic biomaterials such as metals, ceramics, polymers, and composites have been developed [1,2]. Among them, scaffolds based on nanofibers are becoming more and more important [3,4]. These nanofibers can be produced by a broad spectrum of polymers, including biocompatible and biodegradable polymers, such as poly(glycolic acid) (PGA), poly(L-lactic acid) (PLLA), poly(ε caprolactone) (PCL), polyurethanes, polyphosphazenes, collagen, gelatin, and chitosan, as well as copolymers from the corresponding monomers in various compositions [5,6]. This results in the production of a broad spectrum of nanofiber-based scaffolds with different mechanical and biophysical properties. These fibers allow the differentiation of human mesenchymal stem cells (hMSCs) towards osteoblasts in principal [7,8,9]. Furthermore, they can be supplemented with growth factors like bone morphogenetic protein (BMP) or vascular endothelial growth factor (VEGF) in order to enhance osteoinductivity or angiogenesis.BMP-2 is a well-studied member of ...

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Section: Discussionmentioning

confidence: 53%

Section: Construction Of Nanofibers and Characterizationmentioning

confidence: 99%

Section: Gene Expression Analysismentioning

confidence: 99%

mentioning

confidence: 99%

mentioning

confidence: 99%

See 3 more Smart Citations

Lack of Obvious Influence of PLLA Nanofibers on the Gene Expression of BMP-2 and VEGF during Growth and Differentiation of Human Mesenchymal Stem Cells

Schofer

Fuchs-Winkelmann²,

Wack³

et al. 2009

The Scientific World JOURNAL

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Synthetic Enroutes to Engineer Electrospun Scaffolds for Stem Cells and Tissue Regeneration

Ramalingam

Jabbari

Ramakrishna

et al. 2013

Micro and Nanotechnologies in Engineering Stem Cells and Tissues

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Biomimetic Collagen Nanofibrous Materials for Bone Tissue Engineering

2010

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Hierarchical assemblies of nanofibres are ubiquitous in nature. Mineralized type I collagen is the basic building block of hierarchically organized, highly complex structures of bone tissue. As a biomaterial, collagen is widely utilized in biomimetic nanofibrous matrix fabrication due to its inherent biocompatibility and widespread occurrence in nature. Nanotechnology has recently gained a new impetus due to the introduction of the concept of biomimetic nanofibres for tissue regeneration. The emergence of electrospinning techniques provides a new opportunity to fabricate nano‐collagen fibres for bone tissue engineering. By orchestrating major parameters, collagen fibres with different components (pure or blended), sizes (nanometre to micrometre) and surface properties (mineralized or modified by functional bioactive molecules) have been developed and their effects on bone cell adhesion, proliferation, migration and differentiation evaluated. This review briefly introduces natural mineralized collagen structures in bone, biomimetic mineralization and bone grafts, and in vitro mineralization of collagen nanofibres fabricated by using three major techniques – molecular self‐assembly, electrospinning, and phase separation. Their applications in bone tissue engineering are also discussed. We highlight the electrospinning technique in collagen nanofibre fabrication and its great potential for bone tissue regeneration.

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Influence of nanofibers on the growth and osteogenic differentiation of stem cells: a comparison of biological collagen nanofibers and synthetic PLLA fibers

Cited by 40 publications

References 26 publications

Lack of Obvious Influence of PLLA Nanofibers on the Gene Expression of BMP-2 and VEGF during Growth and Differentiation of Human Mesenchymal Stem Cells

Lack of Obvious Influence of PLLA Nanofibers on the Gene Expression of BMP-2 and VEGF during Growth and Differentiation of Human Mesenchymal Stem Cells

Synthetic Enroutes to Engineer Electrospun Scaffolds for Stem Cells and Tissue Regeneration

Biomimetic Collagen Nanofibrous Materials for Bone Tissue Engineering

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