本研究目標是設計一套能針對骨膜提供機械力刺激的生物反應裝置。剪力和壓力這兩種機械力可以單獨或結合調整以刺激骨膜生成軟骨，我們使用水幫浦來產生一個穩定的流場，利用此流場來提供剪力(0~2.21N/m2)，使用空氣幫浦來產生並提供壓力(0~3kg/cm2)。因為骨膜本身的基質就是一天然的支架，所以骨膜是一個容易接受機械力刺激的試件。我們預期此系統可以產生一個類似軟骨的組織，並使用此系統找出生成最佳的似軟骨組織的最佳參數，最終希望此培養出的似軟骨組織能替代天然軟骨來治療關節軟骨的疾病。

The bioreactor in this study was designed to provide mechanical stimulation for culture of chondrogenesis in periosteal explants. The shear and compression forces would be provided by the bioreactor to stimulate the periosteum. A water pump was used to generate shear force (0~2.21N/m2) by a steady flow, and an air pump is used to generate compression force (0~3kg/cm2). The periosteum would accept the stimulus of mechanical force since the matrix of periosteum is a natural scaffold. We expect that the bioreactor could produce a tissue which could function like natural cartilage and help to find the best parameters for culture by a series of experiments.

[1] L. S. Lohmander, "Tissue engineering of cartilage: do we need it, can we do it, is it good and can we prove it?" Novartis Found Symp, vol. 249, pp. 2-10; discussion 10-6, 170-4, 239-41, 2003.
[2] M. Brittberg, A. Lindahl, A. Nilsson, C. Ohlsson, O. Isaksson, and L. Peterson, "Treatment of deep cartilage defects in the knee with autologous chondrocyte transplantation," N Engl J Med, vol. 331, pp. 889-95, 1994.
[3] Y. Miura, J. S. Fitzsimmons, C. N. Commisso, S. H. Gallay, and S. W. O'Driscoll, "Enhancement of periosteal chondrogenesis in vitro. Dose-response for transforming growth factor-beta 1 (TGF-beta 1)," Clin Orthop Relat Res, pp. 271-80, 1994.
[4] S. W. O'Driscoll and R. B. Salter, "The repair of major osteochondral defects in joint surfaces by neochondrogenesis with autogenous osteoperiosteal grafts stimulated by continuous passive motion. An experimental investigation in the rabbit," Clin Orthop Relat Res, pp. 131-40, 1986.
[5] S. W. O'Driscoll, F. W. Keeley, and R. B. Salter, "The chondrogenic potential of free autogenous periosteal grafts for biological resurfacing of major full-thickness defects in joint surfaces under the influence of continuous passive motion. An experimental investigation in the rabbit," J Bone Joint Surg Am, vol. 68, pp. 1017-35, 1986.
[6] S. Nagel-Heyer, C. Goepfert, F. Feyerabend, J. P. Petersen, P. Adamietz, N. M. Meenen, and R. Portner, "Bioreactor cultivation of three-dimensional cartilage-carrier-constructs," Bioprocess Biosyst Eng, vol. 27, pp. 273-80, 2005.
[7] G. Vunjak-Novakovic, "The fundamentals of tissue engineering: scaffolds and bioreactors," Novartis Found Symp, vol. 249, pp. 34-46; discussion 46-51, 170-4, 239-41, 2003.
[8] D. M. Raab-Cullen, M. A. Thiede, D. N. Petersen, D. B. Kimmel, and R. R. Recker, "Mechanical loading stimulates rapid changes in periosteal gene expression," Calcif Tissue Int, vol. 55, pp. 473-8, 1994.

[9] N. Mukherjee, D. B. Saris, F. M. Schultz, L. J. Berglund, K. N. An, and O. D. SW, "The enhancement of periosteal chondrogenesis in organ culture by dynamic fluid pressure," J Orthop Res, vol. 19, pp. 524-30, 2001.
[10] F. Boschetti, G. Pennati, F. Gervaso, G. M. Peretti, and G. Dubini, "Biomechanical properties of human articular cartilage under compressive loads," Biorheology, vol. 41, pp. 159-66, 2004.
[11] T. Ikenoue, M. C. Trindade, M. S. Lee, E. Y. Lin, D. J. Schurman, S. B. Goodman, and R. L. Smith, "Mechanoregulation of human articular chondrocyte aggrecan and type II collagen expression by intermittent hydrostatic pressure in vitro," J Orthop Res, vol. 21, pp. 110-6, 2003.
[12] E. M. Darling and K. A. Athanasiou, "Articular cartilage bioreactors and bioprocesses," Tissue Eng, vol. 9, pp. 9-26, 2003.
[13] R. L. Smith, J. Lin, M. C. Trindade, J. Shida, G. Kajiyama, T. Vu, A. R. Hoffman, M. C. van der Meulen, S. B. Goodman, D. J. Schurman, and D. R. Carter, "Time-dependent effects of intermittent hydrostatic pressure on articular chondrocyte type II collagen and aggrecan mRNA expression," J Rehabil Res Dev, vol. 37, pp. 153-61, 2000.
[14] K. J. Gooch, J. H. Kwon, T. Blunk, R. Langer, L. E. Freed, and G. Vunjak-Novakovic, "Effects of mixing intensity on tissue-engineered cartilage," Biotechnol Bioeng, vol. 72, pp. 402-7, 2001.
[15] R. L. Smith, B. S. Donlon, M. K. Gupta, M. Mohtai, P. Das, D. R. Carter, J. Cooke, G. Gibbons, N. Hutchinson, and D. J. Schurman, "Effects of fluid-induced shear on articular chondrocyte morphology and metabolism in vitro," J Orthop Res, vol. 13, pp. 824-31, 1995.
[16] C. T. Hung, R. L. Mauck, C. C. Wang, E. G. Lima, and G. A. Ateshian, "A paradigm for functional tissue engineering of articular cartilage via applied physiologic deformational loading," Ann Biomed Eng, vol. 32, pp. 35-49, 2004.