Increasing extracellular matrix production in regenerating cartilage with intermittent physiological pressure

Carver, Scott E.; Heath, Carole A.

doi:10.1002/(sici)1097-0290(19990120)62:2<166::aid-bit6>3.3.co;2-b

Cited by 17 publications

(11 citation statements)

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“…The presence of extracellular matrix, which influences the microenvironment of the cells, is not taken into account in this first implementation. Extracellular matrix deposition is a highly complex process, regulated by biochemical and biophysical signals, currently not yet comprehensively investigated (Carver and Heath 1999;Dimicco and Sah 2003). Earlier models generally included significant limitations in modeling extracellular matrix deposition.…”

Section: Discussionmentioning

confidence: 99%

An in silico bioreactor for simulating laboratory experiments in tissue engineering

Galbusera

Cioffi

Raimondi

2008

Biomed Microdevices

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This paper presents a software framework for the computational modeling of tissue engineering experiments, aimed to supplement and extend the empirical techniques currently employed in tissue engineering. The code included a model of cell population dynamics coupled to a finite element model of oxygen diffusion and consumption at the macroscale level, including the scaffold and the culture medium, and at the level of the scaffold microarchitecture. Cells were modeled as discrete entities moving in a continuum space, under the action of adhesion and repulsion forces. Oxygen distribution was calculated with the transient diffusion equation; oxygen consumption by cells was modeled by using the Michaelis-Menten equation. Other phenomena that can be formulated as a differential problem could be added in a straightforward manner to the code, due to the use of a general purpose finite element library. Two scaffold geometries were considered: a fiber scaffold and a scaffold with interconnected spherical pores. Cells were predicted to form clusters and adhere to the scaffold walls. Although the code demonstrated the ability to provide a robust performance, a calibration of the parameters employed in the model, based on specific laboratory experiments, is now required to verify the reliability of the results.

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Section: Discussionmentioning

confidence: 99%

An in silico bioreactor for simulating laboratory experiments in tissue engineering

Galbusera

Cioffi

Raimondi

2008

Biomed Microdevices

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“…7 Representative methylmethacrylate-embedded sections (6 μm thick), from the edges (a, c, e, g) and center (b, d, f, h) of loaded (a, b, e, f) and unloaded (c, d, g, h) constructs cultured at 5% O 2 and 21% O 2 for 34 days, stained with toluidine blue. Bar 1,000 μm (a, b, c, e, g), 200 μm (d, f, h) increasing pressure with regard to the synthesis of cartilagelike tissue (Toyoda et al 2003a,b;Carter et al 2004;Carver and Heath 1999). Furthermore, using finite element modeling, we have found that a confined compression system is necessary to achieve a significant pressure gradient within the highly permeable and elastic porous polyurethane scaffold during load application (Goerke et al 2004).…”

Section: Discussionmentioning

confidence: 99%

Effect of reduced oxygen tension and long-term mechanical stimulation on chondrocyte-polymer constructs

Wernike

Alini

et al. 2007

Cell Tissue Res

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We have investigated the influence of long-term confined dynamic compression and surface motion under low oxygen tension on tissue-engineered cell-scaffold constructs. Porous polyurethane scaffolds (8 mm x 4 mm) were seeded with bovine articular chondrocytes and cultured under normoxic (21% O(2)) or hypoxic (5% O(2)) conditions for up to 4 weeks. By means of our joint-simulating bioreactor, cyclic axial compression (10-20%; 0.5 Hz) was applied for 1 h daily with a ceramic ball, which simultaneously oscillated over the construct surface (+/-25 degrees; 0.5 Hz). Culture under reduced oxygen tension resulted in an increase in mRNA levels of type II collagen and aggrecan, whereas the expression of type I collagen was down-regulated at early time points. A higher glycosaminoglycan content was found in hypoxic than in normoxic constructs. Immunohistochemical analysis showed more intense type II and weaker type I collagen staining in hypoxic than in normoxic cultures. Type II collagen gene expression was slightly elevated after short-term loading, whereas aggrecan mRNA levels were not influenced by the applied mechanical stimuli. Of importance, the combination of loading and low oxygen tension resulted in a further down-regulation of collagen type I mRNA expression, contributing to the stabilization of the chondrocytic phenotype. Histological results confirmed the beneficial effect of mechanical loading on chondrocyte matrix synthesis. Thus, mechanical stimulation combined with low oxygen tension is an effective tool for modulating the chondrocytic phenotype and should be considered when chondrocytes or mesenchymal stem cells are cultured and differentiated with the aim of generating cartilage-like tissue in vitro.

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“…Indeed, an increase in the expression of mRNA for aggrecan and type IIcollagen (Ikenoue et al 2003;Toyoda et al 2003), as well as an increase in 35 SO 4 and [ 3 H]proline incorporation (Parkkinen et al 1993;Hall et al 1991) were shown to occur in chondrocytes in response to the applied hydrostatic compression. In a study of the long-term adaptation to intermittent pressure, chondrocytes subjected to 360 daily pressurization cycles to 3.44 MPa or 6.87 MPa for 5 weeks accumulated approximately tenfold the amount of glycosaminoglycan as non-pressurized controls (Carver and Heath 1999a). There is less information available on the effect of hydrostatic pressure on mesenchymal stem cells, but it was recently reported that 1.0 Hz sinusoidal hydrostatic pressure of 5.03 MPa applied to human mesenchymal progenitor cell aggregates for 4 h/day for 7 days increased proteoglycan and collagen content (Angele et al 2003).…”

Section: Introductionmentioning

confidence: 99%

Cyclic hydrostatic compression stimulates chondroinduction of C3H/10T1/2 cells

Elder

Fulzele

McCulley

2005

Biomech Model Mechanobiol

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While the potential for intermittent hydrostatic pressure to promote cartilaginous matrix synthesis is well established, its potential to influence chondroinduction remains poorly understood. This study examined the effects of relatively short- and long-duration cyclic hydrostatic compression on the chondroinduction of C3H/10T1/2 murine embryonic fibroblasts by recombinant human bone morphogenetic protein-2 (rhBMP-2). Cells were seeded at high density into round bottom wells of a 96-well plate and supplemented with 25 ng/ml rhBMP-2. Experimental cultures were subjected to either 1,800 cycles/day or 7,200 cycles/day of 1 Hz sinusoidal hydrostatic compression to 5 MPa (applied 10 min on/10 min off) for 3 days. Non-pressurized control and experimental cultures were maintained in static culture for an additional 5 days. Cultures were then analyzed for alcian blue staining intensity, DNA and sulfated glycosaminoglycan (sGAG) content, and for the rate of collagen synthesis. Whereas cultures subjected to 1,800 pressure cycles exhibited no significant differences (statistical or qualitative) compared to controls, those subjected to 7,200 cycles stained more intensely with alcian blue, contained nearly twice as much sGAG, and displayed twice the rate of collagen synthesis as non-pressurized controls. This study demonstrates the potential for cyclic hydrostatic compression to stimulate chondrogenic differentiation of the C3H/10T1/2 cell line in a duration-dependent manner.

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Increasing extracellular matrix production in regenerating cartilage with intermittent physiological pressure

Cited by 17 publications

References 0 publications

An in silico bioreactor for simulating laboratory experiments in tissue engineering

An in silico bioreactor for simulating laboratory experiments in tissue engineering

Effect of reduced oxygen tension and long-term mechanical stimulation on chondrocyte-polymer constructs

Cyclic hydrostatic compression stimulates chondroinduction of C3H/10T1/2 cells

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