Design and performance of a bioreactor system for mechanically promoted three-dimensional tissue engineering

Meyer, Ulrich; Büchter, André; Nazer, N.; Wiesmann, Hans Peter

doi:10.1016/j.bjoms.2005.05.001

Cited by 44 publications

(21 citation statements)

References 24 publications

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“…We hypothesized that combined stimuli could increase cell proliferation because several studies had reported that each stimulus has a positive effect to enhance cell proliferation in the specific range of intensity or strain (Rubin et al, 2001;Davisson et al, 2002;Yang et al, 2005;Meyer et al, 2006). The CCK-8 results, however, indicated no significant differences among groups when cells on 3-D PCL/PLLA scaffolds were exposed to cyclic strain, ultrasound, or both simultaneously in our system.…”

Section: Discussioncontrasting

confidence: 37%

“…Such environments involve biochemical, biophysical (e.g., pH, gas exchange, humidity, and temperature), and mechanical stimuli inside as well as outside the body. While biochemical stimuli have been researched extensively, mechanical stimuli have not, although mechanical environments generated by ultrasound or cyclic strain have been studied by many researchers, as these stimuli were found help bone wound healing (Rubin et al, 2001;Davisson et al, 2002;Yang et al, 2005;Meyer et al, 2006).…”

Section: Introductionmentioning

confidence: 99%

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Effects of combined mechanical stimulation on the proliferation and differentiation of pre-osteoblasts

Kang

Lee

et al. 2011

Exp Mol Med

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We observed how combined mechanical stimuli affect the proliferation and differentiation of pre-osteoblasts. For this research, a bioreactor system was developed that can simultaneously stimulate cells with cyclic strain and ultrasound, each of which is known to effectively stimulate bone tissue regeneration. MC3T3-E1 pre-osteoblasts were chosen for bone tissue engineering due to their osteoblast-like characteristics. 3-D scaffolds were fabricated with polycaprolactone (PCL) and poly-L-lactic acid (PLLA) using the salt leaching method. The cells were stimulated by the bioreactor with cyclic strain and ultrasound. The bioreactor was set at a frequency of 1.0 Hz and 10 % strain for cyclic strain and 1.0 MHz and 30 mW/cm 2 for ultrasound. Three experimental groups (ultrasound, cyclic strain, and combined stimulation) and a control group were examined. Each group was stimulated for 20 min/day. Mechanical stimuli did not affect MC3T3-E1 cell proliferation significantly up to 10 days when measured with the cell counting kit-8. However, gene expression analysis of collagen type-I (COL-I), osteocalcin (OC), RUNX2, and osterix (OSX) revealed that the combined mechanical stimulation accelerated the matrix maturation of MC3T3-E1 cells. These results indicate that the combined mechanical stimulation can enhance the differentiation of pre-osteoblasts more efficiently than simple stimuli, in spite of no effect on cell proliferation.

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Section: Discussioncontrasting

confidence: 37%

Section: Introductionmentioning

confidence: 99%

Effects of combined mechanical stimulation on the proliferation and differentiation of pre-osteoblasts

Kang

Lee

et al. 2011

Exp Mol Med

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“…This has led tissue engineers to include mechanical stimulation in their construct formation protocols. [23][24][25][26][27][28][29][30][31][32][33] However, there is little data that elucidates how mechanical forces change the dynamics of fibroblast populations in cell culture systems. This is because most investigations are performed by examining the culture at fixed time points either during or after the mechanical stimulation protocol is complete.…”

Section: Introductionmentioning

confidence: 99%

Design and Performance of an Optically Accessible, Low-Volume, Mechanobioreactor for Long-Term Study of Living Constructs

Paten

Zareian

Saeidi

et al. 2011

Tissue Engineering Part C: Methods

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Currently available bioreactor systems used by tissue engineers permit either direct, high-magnification observation of cell behavior or application of mechanical loads to growing tissue constructs, but not both simultaneously. Further, in most loading bioreactors, the volume of the dead space is not minimized to reduce the cost associated with perfusion media, exogenous stimulatory/inhibitory agents, proteases, and label. We have designed, developed, and tested a bioreactor that simultaneously satisfies the combined requirements of providing (i) controlled tensile mechanical stimulation, (ii) direct high-magnification imaging capability, and (iii) low dead-space volume. This novel mechanostimulatory (uniaxial tensile loading) bioreactor operates on an inverted microscope and permits continuous optical access (up to 600 · ) to a loaded, growing construct for extended periods of time (weeks). The reactor employs an adjustable reaction chamber in which the dead space can be reduced to < 2 mL. The device has been used to cultivate our human primary corneal fibroblastderived, tissue-engineered system for up to 14 days. Using the instrument we have successfully recorded (i) the process of fibroblasts populating, growing to confluence, and stratifying on different substrates; (ii) recorded complex and organized cell sheet motions; and (iii) recorded the behavior of a subpopulation of what appear to be degradative/catabolic cells within our fibroblast culture. The device is capable of providing detailed, long-term, dynamic images of mechanically stimulated cell/matrix interaction that have not been observed previously.

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“…It has been well reported that the mechanical stimuli altered the physiological behaviors of cells [1,2] and mediated the scaffold degradation [3,4].…”

Section: Introductionmentioning

confidence: 99%

A Finite Element Model Revealing Stress Distribution on Tissue Engineering Scaffold in Perfused Bioreactor

2013

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Abstract-It has been well reported that the mechanical stimuli altered the physiological behaviors of cells and mediated the tissue engineering scaffold degradation. However, the accurate local stress was still unknown inside the scaffold since the microstructure is too complicated to study using traditional methods. In this study, we developed a simplified finite element model to evaluate the stress range and distribution on the porous scaffold in perfused bioreactor. Due to our results, the stress on scaffold decreased from inlet to outlet under perfusing while increased under drawing; the stress distribution range on scaffold was closely correlated with the flow rate and scaffold permeability. In conclusion, our study suggests that lower flow rate and higher scaffold permeability generated more uniform mechanical environment for cell growth and scaffold degradation.

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Design and performance of a bioreactor system for mechanically promoted three-dimensional tissue engineering

Cited by 44 publications

References 24 publications

Effects of combined mechanical stimulation on the proliferation and differentiation of pre-osteoblasts

Effects of combined mechanical stimulation on the proliferation and differentiation of pre-osteoblasts

Design and Performance of an Optically Accessible, Low-Volume, Mechanobioreactor for Long-Term Study of Living Constructs

A Finite Element Model Revealing Stress Distribution on Tissue Engineering Scaffold in Perfused Bioreactor

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