The control of human mesenchymal cell differentiation using nanoscale symmetry and disorder

Dalby, Matthew J.; Gadegaard, Nikolaj; Tare, Rahul S.; Andar, Abhay; Riehle, Mathis O.; Herzyk, Paweł; Wilkinson, C. D. W.; Oreffo, Richard O.C.

doi:10.1038/nmat2013

Cited by 2,169 publications

(2,037 citation statements)

References 42 publications

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“…It is well known that surface topography, stiffness, and scaffold porosity play a critical role in cell behavior and tissue growth [22]. To evaluate the potential role of differences in scaffold morphology (PLLA/TGF vs. PLLA/ Ctrl) on AFC anabolism, cells were also cultured in monolayer and exposed to the scaffolds, without any direct contact.…”

Section: Discussionmentioning

confidence: 99%

Bioactive electrospun scaffold for annulus fibrosus repair and regeneration

et al. 2012

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Purpose Annulus fibrosus (AF) tissue engineering is gathering increasing interest for the development of strategies to reduce recurrent disc herniation (DH) rate and to increase the effectiveness of intervertebral disc regeneration strategies. This study evaluates the use of a bioactive microfibrous poly(L-lactide) scaffold releasing Transforming Growth Factor (TGF)-b1 (PLLA/TGF) for the repair and regeneration of damaged AF. Methods The scaffold was synthesized by electrospinning, with a direct incorporation of TGF-b1 into the polymeric solution, and characterized in terms of morphology and drug release profile. Biological evaluation was performed with bovine AF cells (AFCs) that were cultured on the scaffold up to 3 weeks to quantitatively assess glycosaminoglycans and total collagen production, using bare electrospun PLLA as a control. Histological evaluation was performed to determine the thickness of the deposited neo-ECM. Results Results demonstrated that AFCs cultured on PLLA/TGF deposited a significantly greater amount of glycosaminoglycans and total collagen than the control, with higher neo-ECM thickness. Conclusions PLLA/TGF scaffold induced an anabolic stimulus on AFCs, mimicking the ECM three-dimensional environment of AF tissue. This bioactive scaffold showed encouraging results that allow envisaging an application for AF tissue engineering strategies and AF repair after discectomy for the prevention of recurrent DH.

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Section: Discussionmentioning

confidence: 99%

Bioactive electrospun scaffold for annulus fibrosus repair and regeneration

et al. 2012

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“…The physical properties of the scaffolds, namely the chemical, mechanical, and structural properties, may be appropriately designed to support cell expansion 1 or to drive stem cell differentiation. 2,3 Scaffolds have a strategic advantage as therapeutic tissue engineering devices since they are easier to fabricate, are easier to control, are more stable, have lower safety risk and have a lower regulatory burden than growth factors or stem cells. 4 Electrospun polymeric nanofiber scaffolds are of particular interest since they mimic the fibrous structure of native extracellular matrix (ECM).…”

Section: Introductionmentioning

confidence: 99%

Nanofiber scaffolds influence organelle structure and function in bone marrow stromal cells

Tutak

Giri

Bajcsy

et al. 2016

J. Biomed. Mater. Res.

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Tutak, Wojtek; Jyotsnendu, Giri; Bajcsy, Peter; and Simon, Carl G. Jr., "Nanofiber scaffolds influence organelle structure and function in bone marrow stromal cells" (2016 Abstract: Recent work demonstrates that osteoprogenitor cell culture on nanofiber scaffolds can promote differentiation. This response may be driven by changes in cell morphology caused by the three-dimensional (3D) structure of nanofibers. We hypothesized that nanofiber effects on cell behavior may be mediated by changes in organelle structure and function. To test this hypothesis, human bone marrow stromal cells (hBMSCs) were cultured on poly(e-caprolactone) (PCL) nanofibers scaffolds and on PCL flat spuncoat films. After 1 dayculture, hBMSCs were stained for actin, nucleus, mitochondria, and peroxisomes, and then imaged using 3D confocal microscopy. Imaging revealed that the hBMSC cell body (actin) and peroxisomal volume were reduced during culture on nanofibers. In addition, the nucleus and peroxisomes occupied a larger fraction of cell volume during culture on nanofibers than on films, suggesting enhancement of the nuclear and peroxisomal functional capacity. Organelles adopted morphologies with greater 3D-character on nanofibers, where the Z-Depth (a measure of cell thickness) was increased. Comparisons of organelle positions indicated that the nucleus, mitochondria, and peroxisomes were closer to the cell center (actin) for nanofibers, suggesting that nanofiber culture induced active organelle positioning. The smaller cell volume and more centralized organelle positioning would reduce the energy cost of inter-organelle vesicular transport during culture on nanofibers. Finally, hBMSC bioassay measurements (DNA, peroxidase, bioreductive potential, lactate, and adenosine triphosphate (ATP)) indicated that peroxidase activity may be enhanced during nanofiber culture. These results demonstrate that culture of hBMSCs on nanofibers caused changes in organelle structure and positioning, which may affect organelle functional capacity and transport.

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“…Substrate topography comprised of various microand nanofeatures influences cellular behavior [46]. Dalby et al [19] showed that random circular nanostructures with a diameter of approximately 120 nm promoted and directed osteogenic differentiation of HMSCs in the absence of osteogenic supplements in cell culture media, suggesting that nanofeatures alone can stimulate osteogenic differentiation and mineral production in vitro. Various composite scaffolds containing n-HA have been developed with favorable osteogenic responses [36,41,61].…”

Section: Discussionmentioning

confidence: 99%

“…Various composite scaffolds containing n-HA have been developed with favorable osteogenic responses [36,41,61]. For the PLAGA/n-HA scaffolds used in this study, the n-HA nanoparticles incorporated into the microsphere surface had an average size of 100 nm providing a nanotopographical feature that may be beneficial to HMSC growth and differentiation [19]. During in vitro static culture, HMSCs showed greater proliferation on PLAGA/n-HA scaffolds than on PLAGA scaffolds.…”

Section: Discussionmentioning

confidence: 99%

Nano-ceramic Composite Scaffolds for Bioreactor-based Bone Engineering

Deng

Ulery

et al. 2013

Clinical Orthopaedics &Amp; Related Research

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Background Composites of biodegradable polymers and bioactive ceramics are candidates for tissue-engineered scaffolds that closely match the properties of bone. We previously developed a porous, three-dimensional poly (D,L-lactide-co-glycolide) (PLAGA)/nanohydroxyapatite (n-HA) scaffold as a potential bone tissue engineering matrix suitable for high-aspect ratio vessel (HARV) bioreactor applications. However, the physical and cellular properties of this scaffold are unknown. The present study aims to evaluate the effect of n-HA in modulating PLAGA scaffold properties and human mesenchymal stem cell (HMSC) responses in a HARV bioreactor. Questions/purposes By comparing PLAGA/n-HA and PLAGA scaffolds, we asked whether incorporation of n-HA (1) accelerates scaffold degradation and compromises mechanical integrity; (2) promotes HMSC proliferation and differentiation; and (3) enhances HMSC mineralization when cultured in HARV bioreactors. Methods PLAGA/n-HA scaffolds (total number = 48) were loaded into HARV bioreactors for 6 weeks and monitored for mass, molecular weight, mechanical, and morphological changes. HMSCs were seeded on PLAGA/ n-HA scaffolds (total number = 38) and cultured in HARV bioreactors for 28 days. Cell migration, proliferation, osteogenic differentiation, and mineralization were characterized at four selected time points. The same amount of PLAGA scaffolds were used as controls.

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The control of human mesenchymal cell differentiation using nanoscale symmetry and disorder

Cited by 2,169 publications

References 42 publications

Bioactive electrospun scaffold for annulus fibrosus repair and regeneration

Bioactive electrospun scaffold for annulus fibrosus repair and regeneration

Nanofiber scaffolds influence organelle structure and function in bone marrow stromal cells

Nano-ceramic Composite Scaffolds for Bioreactor-based Bone Engineering

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