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Regeneration of Hyaline Cartilage Using a Mechanically-Tuned Chondrocyte-Seeded Biomimetic Tissue-Engineered 3D Scaffold: A Theoretical Approach

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DOI: 10.4236/abb.2014.57074    2,406 Downloads   3,301 Views   Citations
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The limited ability of cartilage tissue to repair itself poses a functionally impairing health problem. While many treatment methods are available, full restoration of the tissue to its original state is rare. Often, complete joint replacement surgery is required to obtain long-term relief. Tissue engineering approaches, however, provide new opportunities for cartilage replacement. They seek to provide mechanisms to repair or replace lost tissue or function. A theoretical method is presented here for regenerating hyaline cartilage in vitro using a chondrocyte-seeded three-dimensional biomimetic engineered scaffold with mechanical properties similar to those occurring naturally. The scaffold composition, type II collagen, aggrecan, hyaluronan, hyaluronan binding protein (for link protein), and BMP-7, were chosen to encourage synthesis of hyaline cartilage by providing a more native environment and signaling cue for the seeded chondrocytes. The scaffold components mimic the macrofibrillar collagen network found in articular cartilage. Type II collagen provides tensile strength, and aggrecan, the predominant proteoglycan, provides compressive strength.

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Hicks, A. (2014) Regeneration of Hyaline Cartilage Using a Mechanically-Tuned Chondrocyte-Seeded Biomimetic Tissue-Engineered 3D Scaffold: A Theoretical Approach. Advances in Bioscience and Biotechnology, 5, 627-632. doi: 10.4236/abb.2014.57074.

Conflicts of Interest

The authors declare no conflicts of interest.


[1] Poole, A.R., Kojima, T., Yasuda, T., Mwale, F., Kobayashi, M. and Laverty, S. (2001) Composition and Structure of Articular Cartilage: A Template for Tissue Repair. Clinical Orthopaedics and Related Research, 391, S26-S33.
[2] O’Driscoll, S.W. (1998) The Healing and Regeneration of Articular Cartilage. Journal of Bone and Joint Surgery, American Volume, 80, 1795-1812.
[3] Pearle, A.D., Warren, R.F. and Rodeo, S.A. (2005) Basic Science of Articular Cartilage and Osteoarthritis. Clinics in Sports Medicine, 24, 1-12.
[4] Temenoff, J.S. and Mikos, A.G. (2000) Review: Tissue Engineering for Regeneration of Articular Cartilage. Biomaterials, 21, 431-440.
[5] Alberts, B., Johnson, A., Lewis, J., Raff, M., Roberts, K. and Walter, P. (2002) Molecular Biology of the Cell. 4th Edtion, Garland Science, New York.
[6] Martini, F.H. (2001) Fundamentals of Anatomy and Physiology. 5th Edition, Prentice Hall, Upper Saddle River.
[7] Kaps, C., Bramlage, C., Smolian, H., Haisch, A., Ungethüm, U., Burmester, G.R., Sittinger, M., Gross, G. and Häupl, T. (2002) Bone Morphogenetic Proteins Promote Cartilage Differentiation and Protect Engineered Artificial Cartilage from Fibroblast Invasion and Destruction. Arthritis and Rheumatism, 46, 149-162.<149::AID-ART10058>3.0.CO;2-W
[8] Shum, L. and Nuckolls, G. (2002) The Life Cycle of Chondrocytes in the Developing Skeleton. Arthritis Research, 4, 94-106.
[9] Daluiski, A., Engstrand, T., Bahamonde, M.E., Gamer, L.W., Agius, E., Stevenson, S.L., Cox, K., Rosen, V. and Lyons, K.M. (2001) Bone Morphogenetic Protein-3 Is a Negative Regulator of Bone Density. Nature Genetics, 27, 84-88.
[10] Klein-Nulend, J., Louwerse, R.T., Heyligers, I.C., Wuisman, P.I., Semeins, C.M., Goei, S.W. and Burger, E.H. (1998) Osteogenic Protein (OP-1, BMP-7) Stimulates Cartilage Differentiation of Human and Goat Perichondrium Tissue in Vitro. Journal of Biomedical Materials Research, 40, 614-620.<614::AID-JBM13>3.0.CO;2-F
[11] Louwerse, R.T., Heyligers, I.C., Klein-Nulend, J., Sugihara, S., van Kampen, G.P., Semeins, C.M., Goei, S.W., de Koning, M.H., Wuisman, P.I. and Burger, E.H. (2000) Use of Recombinant Human Osteogenic Protein-1 for the Repair of Subchondral Defects in Articular Cartilage in Goats. Journal of Biomaterials Research, 49, 506-516.<506::AID-JBM9>3.0.CO;2-A
[12] Chen, J.L., Duan, L., Zhu, W., Xiong, J. and Wang, D. (2014) Extracellular Matrix Production in Vitro in Cartilage Tissue Engineering. Journal of Translational Medicine, 12, 88-96.
[13] Matsiko, A., Levingstone, T.J. and O’Brien, F.J. (2013) Advanced Strategies for Articular Cartilage Defect Repair. Materials, 6, 637-668.
[14] Grande, D.A., Halberstadt, C., Naughton, G., Schwartz, R. and Manji, R. (1997) Evaluation of Matrix Scaffolds for Tissue Engineering of Articular Cartilage Grafts. Journal of Biomedical Materials Research, 34, 211-220.<211::AID-JBM10>3.0.CO;2-L
[15] Pieper, J.S., van der Kraan, P.M., Hafmans, T., Kamp, J., Buma, P., van Susante, J.L.C., van den Berg, W.B., Veerkamp, J.H. and van Kuppevelt, T.H. (2002) Crosslinked Type II Collagen Matrices: Preparation, Characterization, and Potential for Cartilage Engineering. Biomaterials, 23, 3183-3192.
[16] Sherwood, J.K., Riley, S.L., Palazzolo, R., Brown, S.C., Monkhouse, D.C., Coates, M., Griffith, L.G., Landeen, L.K. and Ratcliffe, A. (2002) A Three-Dimensional Osteochondral Composite Scaffold for Articular Cartilage Repair. Biomaterials, 23, 4739-4751.
[17] Hunziker, E.B. (1999) Articular Cartilage Repair: Are the Intrinsic Biological Constraints Undermining This Process Insuperable? Osteoarthritis Cartilage, 7, 15-28.
[18] Roberts, J.J., Nicodemus, G.D., Giunta, S. and Bryant, S.J. (2011) Incorporation of Biomimetic Matrix Molecules in PEG Hydrogels Enhances Matrix Deposition and Reduces Load-Induced Loss of Chondrocyte-Secreted Matrix. Journal of Biomedical Materials Research A, 97A, 281-291.
[19] Ko, C.S., Huang, J.P., Huang, C.W. and Chu, I.M. (2009) Type II Collagen-Chondroitin Sulfate-Hyaluronan Scaffold Cross-Linked by Genipin for Cartilage Tissue Engineering. Journal of Bioscience and Bioengineering, 107, 177-182.
[20] Benders, K.E.M., van Weeren, P.R., Badylak, S.F., Saris, D.B.F., Dhert, W.J.A. and Malda, J. (2013) Extracellular Matrix Scaffolds for Cartilage and Bone Regeneration. Trends in Biotechnology, 31, 169-176.
[21] Yang, Q., Peng, J., Guo, Q., Huang, J., Zhang, L., Yao, J., Yang, F., Wang, S., Xu, W., Wang, A. and Lu, S. (2008) A Cartilage ECM-Derived 3-D Porous Acellular Matrix Scaffold for in Vivo Cartilage Tissue Engineering with PKH26Labeled Chondrogenic Bone Marrow-Derived Mesenchymal Stem Cells. Biomaterials, 29, 2378-2387.
[22] Jin, C.Z., Park, S.R., Choi, B.H., Park, K. and Min, B.H. (2007) In Vivo Cartilage Tissue Engineering Using a Cell-Derived Extracellular Matrix Scaffold. Artificial Organs, 31, 183-192.
[23] Buckwalter, J.A., Mankin, H.J. and Grodzinsky, A.J. (2005) Articular Cartilage and Osteoarthritis. American Academy of Orthopaedic Surgeons Instructional Course Lectures, 54, 465-480.
[24] Allen, J.L., Cooke, M.E. and Alliston, T. (2012) ECM Stiffness Primes the TGFβ Pathway to Promote Chondrocyte Differentiation. Molecular Biology of the Cell, 23, 3731-3742.
[25] Raghunath, J., Salacinski, H.J., Sales, K.M., Butler, P.E. and Seifalian, A.M. (2005) Advancing Cartilage Tissue Engineering: The Application of Stem Cell Technology. Current Opinion in Biotechnology, 16, 503-509.
[26] Knudson, C.B. and Knudson, W. (1993) Hyaluronan-Binding Proteins in Development, Tissue Homeostasis, and Disease. The FASEB Journal, 7, 1233-1241.
[27] Wang, Z., Weitzmann, M.N., Sangadala, S., Hutton, W.C. and Yoon, S.T. (2013) Link Protein N-Terminal Peptide Binds to Bone Morphogenetic Protein (BMP) Type II Receptor and Drives Matrix Protein Expression in Rabbit Intervertebral Disc Cells. The Journal of Biological Chemistry, 288, 28243-28253.
[28] Zhao, G.Q. (2003) Consequences of Knocking out BMP Signaling in the Mouse. Genesis, 35, 43-56.
[29] Hidaka, C., Quitoriano, M., Warren, R.F. and Crystal, R.G. (2001) Enhanced Matrix Synthesis and in Vitro Formation of Cartilage-Like Tissue by Genetically Modified Chondrocytes Expressing BMP-7. Journal of Orthopaedic Research, 19, 751-758.
[30] Pieper, J.S., Oosterhof, A., Dijkstra, P.J., Veerkamp, J.H. and van Kuppevelt, T.H. (1999) Preparation and Characterization of Porous Cross-Linked Collagenous Matrices Containing Bioavailable Chondroitin Sulphate. Biomaterials, 20, 847-858.
[31] Williamson, A.K., Chen, A.C. and Sah, R.L. (2006) Compressive Properties and Function: Composition Relationships of Developing Bovine Articular Cartilage. Journal of Orthopaedic Research, 19, 1113-1121.

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