Due to the high incidence of injury and osteoarthritis and the limited nature of articular cartilage self-repair, alternate means are necessary to replace the damaged tissue and regain an articulating surface that not only stops the progression of disease but functions the same as a healthy articular surface. This study focus on the early stages of damage, particularly when the outer surface layer, the superficial tangential zone, becomes damaged and fibrillation begins. We hope to achieve this by creating a tissue replacement product through tissue engineering using an abundant cell source of mesenchymal stems cells seeded in Collagen Type I scaffolds, and treated not only with chondrogenic growth media in culture, but three different stimulation algorithms to improve structural and functional properties.
The cell source was obtained from bone marrow specimens from healthy human subjects undergoing hip replacement surgery. Cells were expanded, seeded on collagen type I scaffolds and grown statically for 1 week. Following 1 week, constructs were either analyzed for histology, SEM, alignment, indentation, tensile, and aggrecan content with Western Blot analysis or stimulated for 2 additional weeks. Each of the following algorithms comprises one of the three stimulation groups, which were chosen to produce characteristics similar to the superficial tangential zone of articular cartilage: application of compression and tension without offset, application of compression and tension with offset, and tension alone.
Results showed GAG staining from histology in all test groups, however there was more abundance in the stimulated groups. For SEM results there appeared more matrix components and organization in the stimulation groups with both compression and tension. Evaluation of cell alignment showed the test group with both compression and tension without offset trending toward alignment with the direction of applied tension indicating the stimulation algorithm was producing strain effects to cause the cells to preferentially align. Additionally, this group had the best mechanical property outcome. Western blot results showed the group with compression and tension without offset had similar aggrecan content to native articular cartilage results, as well as the other stimulation groups, indicating stimulation aids in producing aggrecan content similar to the superficial tangential zone.
The overall results showed the group stimulated with both compression and tension without offset had the best structure and functional properties of the group. Although the mechanical properties were inferior to native articular cartilage, they were within range of repair tissue. Further exploration with both compression and tension without offset stimulation in longer culturing can enhance these aspects and lead to prevention of further cartilage degradation in patients with early signs of osteoarthritis or damaged articulating surface.
|2002||Davisson T, Kunig S, Chen A, Sah R, Ratcliffe A. Static and dynamic compression modulate matrix metabolism in tissue engineered cartilage. J Orthop Res. July 2002;20(4):842-848.|
|1987||Mak AF, Lai WM, Mow VC. Biphasic indentation of articular cartilage, I: theoretical analysis. J Biomech. 1987;20(7):703-714.|
|1995||Buschmann MD, Gluzband YA, Grodzinsky AJ, Hunziker EB. Mechanical compression modulates matrix biosynthesis in chondrocyte/agarose culture. J Cell Sci. April 1995;108(4):1497-1508.|
|2002||Mow VC, Guo XE. Mechano-electrochemical properties of articular cartilage: their inhomogeneities and anisotropies. Annu Rev Biomed Eng. 2002;4:175-209.|
|1984||Palmoski MJ, Brandt KD. Effects of static and cyclic compressive loading on articular cartilage plugs in vitro. Arthritis Rheum. June 1984;27(6):675-681.|
|2001||Poole AR, Kojima T, Yasuda T, Mwale F, Kobayashi M, Laverty S. Composition and structure of articular cartilage: a template for tissue repair. Clin Orthop Relat Res. October 2001;391(suppl):S26-S33.|
|1993||Setton LA, Zhu W, Mow VC. The biphasic poroviscoelastic behavior of articular cartilage: role of the surface zone in governing the compressive behavior. J Biomech. April–May 1993;26(4-5):581-592.|
|2002||Hunziker EB. Articular cartilage repair: basic science and clinical progress. a review of the current status and prospects. Osteoarthritis Cartilage. June 2002;10(6):432-463.|
|1968||Maroudas A. Physicochemical properties of cartilage in the light of ion exchange theory. Biophys J. May 1968;8(5):575-595.|
|1968||Maroudas A, Bullough P. Permeability of articular cartilage. Nature. September 21, 1968;219(5160):1260-1261.|
|2003||Angele P, Yoo JU, Smith C, Mansour J, Jepsen KJ, Nerlich M, Johnstone B. Cyclic hydrostatic pressure enhances the chondrogenic phenotype of human mesenchymal progenitor cells differentiated in vitro. J Orthop Res. May 2003;21(3):451-457.|
|1989||Sah RL-Y, Kim Y-J, Doong J-YH, Grodzinsky AJ, Plass AHK, Sandy JD. Biosynthetic response of cartilage explants to dynamic compression. J Orthop Res. 1989;7(5):619-636.|
|1976||Mansour JM, Mow VC. The permeability of articular cartilage under compressive strain and at high pressures. J Bone Joint Surg. June 1976;58A(4):509-516.|
|2002||Korhonen RK, Laasanen MS, Töyräs J, Rieppo J, Hirvonen J, Helminen HJ, Jurvelin JS. Comparison of the equilibrium response of articular cartilage in unconfined compression, confined compression and indentation. J Biomech. July 2002;35(7):903-909.|
|2000||Felson DT, Lawrence RC, Dieppe PA, Hirsch R, Helmick CG, Jordan JM, Kington RS, Lane NE, Nevitt MC, Zhang Y, Sowers M, McAlindon T, Spector TD, Poole AR, Yanovski SZ, Ateshian G, Sharma L, Buckwalter JA, Brandt KD, Fries JF. Osteoarthritis: new insights, I: the disease and its risk factors. Ann Intern Med. October 17, 2000;133(8):635-646.|
|1968||Maroudas A, Bullough P, Swanson SAV, Freeman MAR. The permeability of articular cartilage. J Bone Joint Surg. February 1968;50B(1):166-177.|
|2006||Mauck RL, Yuan X, Tuan RS. Chondrogenic differentiation and functional maturation of bovine mesenchymal stem cells in long-term agarose culture. Osteoarthritis Cartilage. February 2006;14(2):179-189.|
|2007||Mauck RL, Byers BA, Yuan X, Tuan RS. Regulation of cartilaginous ECM gene transcription by chondrocytes and MSCs in 3D culture in response to dynamic loading. Biomech Model Mechanobiol. January 2007;6(1-2):113-125.|
|1976||Hori RY, Mockros LF. Indentation tests of human articular cartilage. J Biomech. 1976;9(4):259-268.|
|2004||Vanderploeg EJ, Imler SM, Brodkin KR, Garcı́a AJ, Levenston ME. Oscillatory tension differentially modulates matrix metabolism and cytoskeletal organization in chondrocytes and fibrochondrocytes. J Biomech. December 2004;37(12):1941-1952.|
|2002||Hunziker EB, Quinn TM, Häuselmann H-J. Quantitative structural organization of normal adult human articular cartilage. Osteoarthritis Cartilage. July 2002;10(7):564-572.|
|1978||Hayes WC, Bodine AJ. Flow-independent viscoelastic properties of articular cartilage matrix. J Biomech. 1978;11(8-9):407-419.|
|2005||Li W-J, Tuli R, Huang X, Laquerriere P, Tuan RS. Multilineage differentiation of human mesenchymal stem cells in a three-dimensional nanofibrous scaffold. Biomaterials. September 2005;26(25):5158-5166.|
|1991||Athanasiou KA, Rosenwasser MP, Buckwalter JA, Malinin TI, Mow VC. Interspecies comparisons of in situ intrinsic mechanical properties of distal femoral cartilage. J Orthop Res. May 1991;9(3):330-340.|
|1982||Jones IL, Klämfeldt A, Sandström T. The effect of continuous mechanical pressure upon the turnover of articular cartilage proteoglycans in vitro. Clin Orthop Relat Res. May 1982;165:283-289.|
|1990||Schmidt MB, Mow VC, Chun LE, Eyre DR. Effects of proteoglycan extraction on the tensile behavior of articular cartilage. J Orthop Res. May 1990;8(3):353-363.|
|1980||Lai WM, Mow VC. Drag-induced compression of articular cartilage during a permeation experiment. Biorheology. 1980;17(1-2):111-123.|
|1975||Maroudas A. Biophysical chemistry of cartilaginous tissues with special reference to solute and fluid transport. Biorheology. 1975;12(3-4):233-248.|
|2004||Huang CC, Hagar KL, Frost LE, Sun Y, Cheung HS. Effects of cyclic compressive loading on chondrogenesis of rabbit bone-marrow derived mesenchymal stem cells. Stem Cells. May 2004;22(3):313-323.|