The Effect of a Long-Term Cyclic Strain on Human Dermal Fibroblasts Cultured in a Bioreactor on Chitosan-Based Scaffolds for the Development of Tissue Engineered Artificial Dermis

Sae-Hwan Lim; Youngsook Son; Chun-Ho Kim; Heungsoo Shin; Jong Il Kim

Macromolecular Research, Vol.15, No.4, 370-378, June, 2007

Sae-Hwan Lim, Youngsook Son, Chun-Ho Kim^†, Heungsoo Shin¹, and Jong Il Kim²

Laboratory of Tissue Engineering, Korea Institute of Radiological and Medical Sciences, Seoul 139-240, Korea
¹Department of Bioengineering, Hanyang University, Seoul 133-791, Korea
²Colledge of Natural Sciences, Seoul Women’s University, Seoul 139-774, Korea

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Mechanical stimulation is known to activate several cellular signal transduction pathways, leading to the induction of signaling molecules and extracellular matrix (ECM) proteins, thereby modulating cellular activities, such as proliferation and survival. In this study, primary human dermal fibroblasts (HDFs) were seeded onto chitosan-based scaffolds, and then cultured for 3 weeks in a bioreactor under a cyclic strain of 1 Hz frequency. Compared to control samples cultured under static conditions, the application of a cyclic strain stimulated the proliferation of HDFs in 1 week, and by week 3 the thickness of the cell/scaffold composites increased 1.56 fold. Moreover, immunohistochemical staining of the culture media obtained from the cell/scaffold samples subjected to the cyclic strain, revealed increases in the expression and secretion of ECM proteins, such as fibronectin and collagen. These results suggest that the preconditioning of cell/scaffold composites with a cyclic strain may enhance the proliferation of HDFs, and even facilitate integration of the engineered artificial dermal tissue into the host graft site.

Keywords:skin;chitosan;fibroblast;strain;artificial dermis;extracellular matrix

[References]

Williams D, ESB Satellite Consensus Conference, Sorrento, 9 (2005)
Kim BS, Mooney DJ, J. Biomech. Eng., 122, 210 (2000)
Akhouayri O, Lafage-Proust MH, Rattner A, Laroche N, Caillot-Augusseau A, Alexandre C, Vico L, J. Cell. Biochem., 76, 217 (1999)
Kim BS, Nikolovski J, Bonadio J, Mooney DJ, Nature Biotech., 17, 979 (1999)
Nguyen KT, Frye SR, Eskin SG, Patterson C, Runge MS, McIntire LV, Hypertension, 38, 1038 (2001)
Lee EK, Lee JS, Park HS, Kim CH, Gin YJ, Son Y, Tissue Eng. and Regen. Med., 2, 29 (2005)
Park HS, Kim YY, Kim CH, Son Y, Tissue Eng., submit (2006)
Lahiji A, Sohrabi A, Hungerford DS, Frondoza CG, J. Biomed. Mater. Res., 51, 586 (2000)
Eser Elcin A, Elcin YM, Pappas GD, Neurol. Res., 20, 648 (1998)
Varum KM, Myhr MM, Hjerde RJ, Smidsrod O, Carbohydr. Res., 299, 99 (1997)
Taravel MN, Domard A, Biomaterials, 17, 451 (1996)
Denuziere A, Ferrier D, Damour O, Domard A, Biomaterials, 19, 1275 (1998)
Chatelet C, Damour O, Domald A, Biomaterials, 22, 262 (2001)
Kim CH, Park HS, Gin YJ, Son YS, Lim SH, Choi YJ, Park KS, Park CW, Macromol. Res., 12(4), 367 (2004)
Zhan RG, Ma PX, J. Biomed. Mater. Res., 44, 446 (1999)
Park HS, Kang HJ, Kim CH, Kim CH, Han ES, Han KB, Kim TH, Gin YJ, Son YS, Tissue Eng., 10, 343 (2004)
Eshel H, Lanir Y, Ann. Biomed. Eng., 29, 164 (2001)
Grunkemeier JM, Tsai WB, McFarland CD, Horbett TA, Biomaterials, 21, 2243 (2000)
Fernandes DJ, Bonacci JV, Stewart AG, Curr. Drug Targets, 7, 567 (2006)
Mao Y, Schwarzbauer JE, Matrix Biol., 24, 389 (2005)
Gallant ND, Michael KE, Garcia AJ, Mol. Biol. Cell., 16, 4329 (2005)
Hynes R, Cell, 110, 673 (2002)
Garcia AJ, Boettiger D, Biomaterials, 20, 2427 (1999)
Chiquet M, Matrix Biol., 18, 417 (1999)
Inoh H, Ishiguro N, Sawazaki S, Amma H, Miyazu M, Iwata H, Sokabe M, Naruse K, Faseb J., 16, 405 (2002)

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[1] Williams D, ESB Satellite Consensus Conference, Sorrento, 9 (2005)

[2] Kim BS, Mooney DJ, J. Biomech. Eng., 122, 210 (2000)

[3] Akhouayri O, Lafage-Proust MH, Rattner A, Laroche N, Caillot-Augusseau A, Alexandre C, Vico L, J. Cell. Biochem., 76, 217 (1999)

[4] Kim BS, Nikolovski J, Bonadio J, Mooney DJ, Nature Biotech., 17, 979 (1999)

[5] Nguyen KT, Frye SR, Eskin SG, Patterson C, Runge MS, McIntire LV, Hypertension, 38, 1038 (2001)

[6] Lee EK, Lee JS, Park HS, Kim CH, Gin YJ, Son Y, Tissue Eng. and Regen. Med., 2, 29 (2005)

[7] Park HS, Kim YY, Kim CH, Son Y, Tissue Eng., submit (2006)

[8] Lahiji A, Sohrabi A, Hungerford DS, Frondoza CG, J. Biomed. Mater. Res., 51, 586 (2000)

[9] Eser Elcin A, Elcin YM, Pappas GD, Neurol. Res., 20, 648 (1998)

[10] Varum KM, Myhr MM, Hjerde RJ, Smidsrod O, Carbohydr. Res., 299, 99 (1997)

[11] Taravel MN, Domard A, Biomaterials, 17, 451 (1996)

[12] Denuziere A, Ferrier D, Damour O, Domard A, Biomaterials, 19, 1275 (1998)

[13] Chatelet C, Damour O, Domald A, Biomaterials, 22, 262 (2001)

[14] Kim CH, Park HS, Gin YJ, Son YS, Lim SH, Choi YJ, Park KS, Park CW, Macromol. Res., 12(4), 367 (2004)

[15] Zhan RG, Ma PX, J. Biomed. Mater. Res., 44, 446 (1999)

[16] Park HS, Kang HJ, Kim CH, Kim CH, Han ES, Han KB, Kim TH, Gin YJ, Son YS, Tissue Eng., 10, 343 (2004)

[17] Eshel H, Lanir Y, Ann. Biomed. Eng., 29, 164 (2001)

[18] Grunkemeier JM, Tsai WB, McFarland CD, Horbett TA, Biomaterials, 21, 2243 (2000)

[19] Fernandes DJ, Bonacci JV, Stewart AG, Curr. Drug Targets, 7, 567 (2006)

[20] Mao Y, Schwarzbauer JE, Matrix Biol., 24, 389 (2005)

[21] Gallant ND, Michael KE, Garcia AJ, Mol. Biol. Cell., 16, 4329 (2005)

[22] Hynes R, Cell, 110, 673 (2002)

[23] Garcia AJ, Boettiger D, Biomaterials, 20, 2427 (1999)

[24] Chiquet M, Matrix Biol., 18, 417 (1999)

[25] Inoh H, Ishiguro N, Sawazaki S, Amma H, Miyazu M, Iwata H, Sokabe M, Naruse K, Faseb J., 16, 405 (2002)