A Novel Bioreactor for the Dynamic Stimulation and Mechanical Evaluation of Multiple Tissue-Engineered Constructs

Lujan, Trevor J.; Wirtz, Kyle M.; Bahney, Chelsea S.; Madey, Steven M.; Johnstone, Brian; Bottlang, Michael

doi:10.1089/ten.tec.2010.0381

Cited by 44 publications

(34 citation statements)

References 35 publications

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“…Dynamic culture, replacing the traditional static culture, has become a new trend in bone tissue engineering [15]. However, the existing bioreactors for tissue engineering applications still have some problems.…”

Section: Discussionmentioning

confidence: 99%

Three-dimensional dynamic culture of pre-osteoblasts seeded in HA-CS/Col/nHAP composite scaffolds and treated with α-ZAL

Liu¹,

Guo²,

Chen³

et al. 2012

ABBS

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Pre-osteoblast MC3T3-E1 cells were cultured in hyaluronic acid-modified chitosan/collagen/nano-hydroxyapatite (HA-CS/Col/nHAP) composite scaffolds and treated with phytoestrogen a-zearalanol (a-ZAL) to improve bone tissue formation for bone tissue engineering. Perfusion and dynamic strain were applied to three-dimensional (3D) cultured cells, which simulates mechanical microenvironment in bone tissue and solves mass transfer issues. The morphology of cell-scaffold constructs in vitro was then examined and markers of osteogenesis were assessed by immunohistochemistry staining and western blotting. The results showed that cells expanded their pseudopodia in an irregular manner and dispersed along the walls in 3D-dynamic culture. Osteogenic phenotype was increased or maintained by enhanced collagen I (COLI) levels, decreased osteopontin expression and having little effect on osteocalcin expression during the 12 days of in vitro culture. In response to a-ZAL, the cell-scaffold constructs showed inhibited cellular proliferation, enhanced the alkaline phosphatase (ALP) activity and increased ratio of osteoprotegerin to receptor activator of nuclear factor kappa B (NF-kB) ligand (RANKL). Application of perfusion and dynamic strain to cells-scaffold constructs treated with a-ZAL represents a promising approach in the studies of osteogenesis stimulation of bone tissue engineering.

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Section: Discussionmentioning

confidence: 99%

Three-dimensional dynamic culture of pre-osteoblasts seeded in HA-CS/Col/nHAP composite scaffolds and treated with α-ZAL

Liu¹,

Guo²,

Chen³

et al. 2012

ABBS

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“…To our knowledge, only three indirect compression systems have been developed, which utilize noncontact magnetically driven pressure actuators. 10,35,36 However, these devices do not utilize the magnetic field as a mode of biophysical stimulation; instead, the magnetic fields are solely to actuate mechanical loading. The range of magneto-stimulation that can be applied in our system is modular and scalable, since the size and strength of the magnets can be varied without major revisions of the peripheral equipment or technology.…”

Section: Figmentioning

confidence: 99%

“…Since 1939, when Glucksmann built the first mechanostimulation device, many devices have been developed to apply mechanical stimuli to cartilage explants and engineered constructs. Lujan et al 10 reported over 205 cartilage engineering articles, which applied mechanical stimulation, 29% of which had the capacity to quantify material properties. Interestingly, most of these devices are only capable of applying a single type of mechanical stimulus, including compressive loading, [11][12][13][14][15][16][17] bending or tensile stress, [18][19][20][21] shear stress, [22][23][24] and hydrostatic pressure.…”

Section: Introductionmentioning

confidence: 99%

The Design and Development of a High-Throughput Magneto-Mechanostimulation Device for Cartilage Tissue Engineering

BradyMariea

VazeReva

Amin

et al. 2014

Tissue Engineering Part C: Methods

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To recapitulate the in vivo environment and create neo-organoids that replace lost or damaged tissue requires the engineering of devices, which provide appropriate biophysical cues. To date, bioreactors for cartilage tissue engineering have focused primarily on biomechanical stimulation. There is a significant need for improved devices for articular cartilage tissue engineering capable of simultaneously applying multiple biophysical (electrokinetic and mechanical) stimuli. We have developed a novel high-throughput magnetomechanostimulation bioreactor, capable of applying static and time-varying magnetic fields, as well as multiple and independently adjustable mechanical loading regimens. The device consists of an array of 18 individual stations, each of which uses contactless magnetic actuation and has an integrated Hall Effect sensing system, enabling the real-time measurements of applied field, force, and construct thickness, and hence, the indirect measurement of construct mechanical properties. Validation tests showed precise measurements of thickness, within 14 mm of gold standard calliper measurements; further, applied force was measured to be within 0.04 N of desired force over a half hour dynamic loading, which was repeatable over a 3-week test period. Finally, construct material properties measured using the bioreactor were not significantly different ( p = 0.97) from those measured using a standard materials testing machine. We present a new method for articular cartilage-specific bioreactor design, integrating combinatorial magnetomechanostimulation, which is very attractive from functional and cost viewpoints.

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“…The range in our device is *30 · more than the Aufderheide design 10 and 7 · more than the Lujan device. 14 In mimicking extreme rates of stress change, our device is a compromise between other designs. Finally, our design implements a linear encoder that is independent of sensing elements which reduces the complexity of further device enhancements.…”

Section: Design Comparisonmentioning

confidence: 99%

“…10,11 A stimulator design recently reported by Lujan et al has taken into consideration the adaptability to standard disposable tissue culture trays and demonstrated the capability to measure force on individual samples through the use of dedicated electromagnetic actuators. 14 However, due to the size of the electromagnetic actuators, they are limited to a six-well plate. This shortcoming restricts stimulation and constructs evaluation throughput.…”

mentioning

confidence: 99%

Design and Validation of a Compressive Tissue Stimulator with High-Throughput Capacity and Real-Time Modulus Measurement Capability

Salvetti

Pino²,

Manuel³

et al. 2012

Tissue Engineering Part C: Methods

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Mechanical stimulation has been shown to impact the properties of engineered hyaline cartilage constructs and is relevant for engineering of cartilage and osteochondral tissues. Most mechanical stimulators developed to date emphasize precision over adaptability to standard tissue culture equipment and protocols. The realization of mechanical characteristics in engineered constructs approaching native cartilage requires the optimization of complex variables (type of stimulus, regimen, and bimolecular signals). We have proposed and validated a stimulator design that focuses on high construct capacity, compatibility with tissue culture plastic ware, and regimen adaptability to maximize throughput. This design utilizes thin force sensors in lieu of a load cell and a linear encoder to verify position. The implementation of an individual force sensor for each sample enables the measurement of Young's modulus while stimulating the sample. Removable and interchangeable Teflon plungers mounted using neodymium magnets contact each sample. Variations in plunger height and design can vary the strain and force type on individual samples. This allows for the evaluation of a myriad of culture conditions and regimens simultaneously. The system was validated using contact accuracy, and Young's modulus measurements range as key parameters. Contact accuracy for the system was excellent within 1.16% error of the construct height in comparison to measurements made with a micrometer. Biomaterials ranging from bioceramics (cancellous bone, 123 MPa) to soft gels (1% agarose, 20 KPa) can be measured without any modification to the device. The accuracy of measurements in conjunction with the wide range of moduli tested demonstrate the unique characteristics of the device and the feasibility of using this device in mapping real-time changes to Young's modulus of tissue constructs (cartilage, bone) through the developmental phases in ex vivo culture conditions.

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A Novel Bioreactor for the Dynamic Stimulation and Mechanical Evaluation of Multiple Tissue-Engineered Constructs

Cited by 44 publications

References 35 publications

Three-dimensional dynamic culture of pre-osteoblasts seeded in HA-CS/Col/nHAP composite scaffolds and treated with α-ZAL

Three-dimensional dynamic culture of pre-osteoblasts seeded in HA-CS/Col/nHAP composite scaffolds and treated with α-ZAL

The Design and Development of a High-Throughput Magneto-Mechanostimulation Device for Cartilage Tissue Engineering

Design and Validation of a Compressive Tissue Stimulator with High-Throughput Capacity and Real-Time Modulus Measurement Capability

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A Novel Bioreactor for the Dynamic Stimulation and Mechanical Evaluation of Multiple Tissue-Engineered Constructs

Cited by 44 publications

References 35 publications

Three-dimensional dynamic culture of pre-osteoblasts seeded in HA-CS/Col/nHAP composite scaffolds and treated with &alpha;-ZAL

Three-dimensional dynamic culture of pre-osteoblasts seeded in HA-CS/Col/nHAP composite scaffolds and treated with &alpha;-ZAL

The Design and Development of a High-Throughput Magneto-Mechanostimulation Device for Cartilage Tissue Engineering

Design and Validation of a Compressive Tissue Stimulator with High-Throughput Capacity and Real-Time Modulus Measurement Capability

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Product

Resources

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Three-dimensional dynamic culture of pre-osteoblasts seeded in HA-CS/Col/nHAP composite scaffolds and treated with α-ZAL

Three-dimensional dynamic culture of pre-osteoblasts seeded in HA-CS/Col/nHAP composite scaffolds and treated with α-ZAL