Skip to main content

Advertisement

SpringerLink
Log in

Adult Stem Cell Driven Genesis of Human-Shaped Articular Condyle

  • Published:
Annals of Biomedical Engineering Aims and scope Submit manuscript

Abstract

Uniform design of synovial articulations across mammalian species is challenged by their common susceptibility to joint degeneration. The present study was designed to investigate the possibility of creating human-shaped articular condyles by rat bone marrow-derived mesenchymal stem cells (MSCs) encapsulated in a biocompatible poly(ethylene glycol)-based hydrogel. Rat MSCs were harvested, expanded in culture, and treated with either chondrogenic or osteogenic supplements. Rat MSC-derived chondrogenic and osteogenic cells were loaded in hydrogel suspensions in two stratified and yet integrated hydrogel layers that were sequentially photopolymerized in a human condylar mold. Harvested articular condyles from 4-week in vivo implantation demonstrated stratified layers of chondrogenesis and osteogenesis. Parallel in vitro experiments using goat and rat MSCs corroborated in vivo data by demonstrating the expression of chondrogenic and osteogenic markers by biochemical and mRNA analyses. Ex vivo incubated goat MSC-derived chondral constructs contained cartilage-related glycosaminoglycans and collagen. By contrast, goat MSC-derived osteogenic constructs expressed alkaline phosphatase and osteonectin genes, and showed escalating calcium content over time. Rat MSC-derived osteogenic constructs were stiffer than rat MSC-derived chondrogenic constructs upon nanoindentation with atomic force microscopy. These findings may serve as a primitive proof of concept for ultimate tissue-engineered replacement of degenerated articular condyles via a single population of adult mesenchymal stem cells.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

REFERENCES

  1. Abukawa, H., H. Terai, D. Hannouche, J. P. Vacanti, L. B. Kaban, and M. J. Troulis. Formation of a mandibular condyle in vitro by tissue engineering. J.Oral Maxillofac.Surg. 61:94–100, 2003.

    Google Scholar 

  2. Ahmad, C. S., Z. A. Cohen, W. N. Levine, G. A. Ateshian, and V. C. Mow. Biomechanical and topographic considerations for autologous osteochondral grafting in the knee. Am.J.Sports Med. 29:201–206, 2001.

    Google Scholar 

  3. Ahmad, C. S., W. B. Guiney, and C. J. Drinkwater. Evaluation of donor site intrinsic healing response in autologous osteochondral grafting of the knee. Arthroscopy 18:95–98, 2002.

    Google Scholar 

  4. Alhadlaq, A., and J. J. Mao. Tissue-engineered neogenesis of human-shaped mandibular condyle from rat mesenchymal stem cells. J.Dent.Res. 82:951–956, 2003.

    Google Scholar 

  5. Alsberg, E., K. W. Anderson, A. Albeiruti, J. A. Rowley, and D. J. Mooney. Engineering growing tissues. Proc.Natl.Acad.Sci.U.S.A. 17:12025–12030, 2002.

    Google Scholar 

  6. Athanasiou, K. A., A. Agarwal, A. Muffoletto, F. J. Dzida, G. Constantinides, and M. Clem. Biomechanical properties of hip cartilage in experimental animal models. Clin.Orthop. 316:254–266, 1995.

    Google Scholar 

  7. Aubin, J. E. Advances in the osteoblast lineage. Biochem.Cell.Biol. 76:899–910, 1998.

    Google Scholar 

  8. Awad, H. A., D. L. Butler, G. P. Boivin, F. N. Smith, P. Malaviya, B. Huibregtse, and A. I. Caplan. Autologous mesenchymal stem cell-mediated repair of tendon. Tissue Eng. 5:267–277, 1999.

    Google Scholar 

  9. Bentley, G., and R. B. Greer. Homotransplantation of isolated epiphyseal and articular cartilage chondrocytes into joint sur-faces of rabbits. Nature 230:385–388, 1971.

    Google Scholar 

  10. Bruder, S. P., N. Jaiswal, N. S. Ricalton, J. D. Mosca, K. H. Kraus, and S. Kadiyala. Mesenchymal stem cells in osteobiology and applied bone regeneration. Clin.Orthop. 355:247S–256S, 1998.

    Google Scholar 

  11. Burdick, J. A., and K. S. Anseth. Photoencapsulation of os-teoblasts in injectable RGD-modified PEG hydrogels for bone tissue engineering. Biomaterials 23:4315–4323, 2002.

    Google Scholar 

  12. Caplan, A. I. Mesenchymal stem cells. J.Orthop.Res. 9:641, 1991.

    Google Scholar 

  13. Carter, D. R., G. S. Beaupre, N. J. Giori, and J. A. Helms. Mechanobiology of skeletal regeneration. Clin.Orthop. 355:41S–55S, 1998.

    Google Scholar 

  14. Caterson, E. J., L. J. Nesti, W. J. Li, K. G. Danielson, T. J. Albert, A. R. Vaccaro, and R. S. Tuan. Three-dimensional car-tilage formation by bone marrow-derived cells seeded in poly-lactide/ alginate amalgam. J.Biomed.Mater.Res. 57:394–403, 2001.

    Google Scholar 

  15. Deschamps, A. A., D. W. Grijpma, and J. Feijen. Phase separation and physical properties of PEO-containing poly(ether ester amide)s. J.Biomater.Sci.Polym.Ed. 13:1337–1352, 2002.

    Google Scholar 

  16. Elisseeff, J., W. McIntosh, K. Anseth, S. Riley, P. Ragan, and R. Langer. Photoencapsulation of chondrocytes in poly(ethylene oxide)-based semi-interpenetrating networks. J.Biomed.Mater.Res. 51:164–171, 2000.

    Google Scholar 

  17. Elisseeff, J., W. McIntosh, K. Fu, B. T. Blunk, and R. Langer. Controlled-release of IGF-I and TGF-beta1 in a photopolymerizing hydrogel for cartilage tissue engineering. J.Orthop.Res. 19:1098–1104, 2001.

    Google Scholar 

  18. Freed, L. E., D. A. Grande, Z. Lingbin, J. Emmanual, J. C. Marquis, and R. Langer. Joint resurfacing using allograft chondrocytes and synthetic biodegradable polymer scaffolds. J.Biomed.Mater.Res. 28:891–899, 1994.

    Google Scholar 

  19. Froimson, M. I., A. Ratcliffe, T. R. Gardner, and V. C. Mow. Differences in patellofemoral joint cartilage material properties and their significance to the etiology of cartilage surface fibrillation. Osteoarth.Cartil. 5:377–386, 1997.

    Google Scholar 

  20. Fu, J., J. Fiegel, E. Krauland, and J. Hanes. Newpolymeric carriers for controlled drug delivery following inhalation or injection. Biomaterials 23:4425–4433, 2002.

    Google Scholar 

  21. Gao, J., J. E. Dennis, L. A. Solchaga, A. S. Awadallah, V. M. Goldberg, and A. I. Caplan. Tissue-engineered fabrication of an osteochondral composite graft using rat bone marrow-derived mesenchymal stem cells. Tissue Eng. 7:363–371, 2001.

    Google Scholar 

  22. Gay, S., S. Kuchen, R. E. Gay, and M. Neidhart. Cartilage de-struction in rheumatoid arthritis. Ann.Rheum.is. 61:87, 2002.

    Google Scholar 

  23. Goldberg, V. M., and A. I. Caplan. Biological resurfacing: An alternative to total joint arthroplasty. Orthopedics 17:819–821, 1994.

    Google Scholar 

  24. Goldstein, A. S. Effects of cell concentration and growth period on articular and ear chondrocyte transplants for tissue engineering. Plast.Reconstr.Surg. 108:392–402, 2001.

    Google Scholar 

  25. Goldstein, S. A. Tissue engineering: Functional assessment and clinical outcome. Ann.N.Y.Acad.Sci. 961:183–192, 2002.

    Google Scholar 

  26. Gravallese, E. M. Bone destruction in arthritis. Ann.Rheum.Dis. 61:84–86, 2002.

    Google Scholar 

  27. Grodzinsky, A. J., M. E. Levenston, M. Jin, and E. H. Frank. Cartilage tissue remodeling in response to mechanical forces. Ann.Rev.Biomed.Eng. 2:691–713, 2000.

    Google Scholar 

  28. Guilak, F., and V. C. Mow. The mechanical environment of the chondrocyte: A biphasic finite element model of cell–matrix interactions in articular cartilage. J.Biomech. 33:1663–1673, 2000.

    Google Scholar 

  29. Hanada, K., L. A. Solchaga, A. I. Caplan, T. M. Hering, V. M. Goldberg, J. U. Yoo, and B. Johnstone. BMP-2 induction and TGF-beta1 modulation of rat periosteal cell chondrogenesis. J.Cell.Biochem. 81:284–294, 2001.

    Google Scholar 

  30. Hangody, L., P. Feczko, L. Bartha, G. Bodo, and G. Kish. Mosaicplasty for the treatment of articular defects of the knee and ankle. Clin.Orthop. 391:328S–336S, 2001.

    Google Scholar 

  31. Hollinger, J. O., J. M. Schmitt, D. C. Buck, R. Shannon, S. P. Joh, H. D. Zegzula, and J. Wozney. Recombinant human bone morphogenetic protein-2 and collagen for bone regeneration. J.Biomed.Mater.Res. 43:356–364, 1998.

    Google Scholar 

  32. Hong, L., S. Miyamoto, N. Hashimoto, and Y. Tabata. Syner-gistic effect of gelatin microspheres incorporating TGF-beta1 and a physical barrier for fibrous tissue infiltration on skull bone formation. J.Biomater.Sci.Polym.Ed. 11:1357–1369, 2000.

    Google Scholar 

  33. Hu, K., P. Radhakrishnan, R. V. Patel, and J. J. Mao. Regional structural and viscoelastic properties of fibrocartilage upon dy-namic nanoindentation of the articular condyle. J.Struct.Biol. 136:470–475, 2001.

    Google Scholar 

  34. Hunziker, E. B. Articular cartilage repair: Basic science and clinical progress. A review of the current status and prospects. Osteoarth.Cartil. 10:432–463, 2002.

    Google Scholar 

  35. Isogai, N., W. Landis, T. H. Kim, L. C. Gerstenfeld, J. Upton, and J. P. Vacanti. Formation of phalanges and small joints by tissue-engineering. J.Bone Joint Surg.Am. 81:306–316, 1999.

    Google Scholar 

  36. Kopher, R. A., and J. J. Mao. Sutural growth modulated by the oscillatory component of micromechanical strain. J.Bone Miner.Res. 18:521–528, 2003.

    Google Scholar 

  37. Korhonen, R. K., M. S. Laasanen, J. Toyras, J. Rieppo, J. Hirvonen, H. J. Helminen, and J. S. Jurvelin. Comparison of the equilibrium response of articular cartilage in unconfined compression, confined compression and indentation. J.Biomech. 35:903–909, 2002.

    Google Scholar 

  38. Krebsbach, P. H., S. A. Kuznetsov, P. Bianco, and P. G. Robey. Bone marrow stromal cells: Characterization and clinical application. Crit.Rev.Oral Biol.Med. 10:165–181, 1999.

    Google Scholar 

  39. Lammi, M., and M. Tammi. Densitometric assay of nanogram quantities of proteoglycans precipitated on nitrocellulose mem-brane with safranin O. Anal.Biochem. 168:352–357, 1988.

    Google Scholar 

  40. Langer, R. S., and J. P. Vacanti. Tissue engineering: The chal-lenges ahead. Science 280:86–89, 1999. 41 Lee, K. Y., and D. J. Mooney. Hydrogels for tissue engineering. Chem.Rev. 101:1869–1879, 2001.

    Google Scholar 

  41. Lietman, S. A., S. Miyamoto, P. R. Brown, N. Inoue, and A. H. Reddi. The temporal sequence of spontaneous repair of os-teochondral defects in the knees of rabbits is dependent on the geometry of the defect. J.Bone Joint Surg.Br. 84:600–606, 2002.

    Google Scholar 

  42. Lutolf, M. P., F. E. Weber, H. G. Schmoekel, J. C. Schense, T. Kohler, R. Muller, and J. A. Hubbell. Repair of bone defects using synthetic mimetics of collagenous extracellular matrices. Nat.Biotechnol. 21:513–518, 2003.

    Google Scholar 

  43. MacKenzie, T. C., and A. W. Flake. Human mesenchymal stem cells: Insights from a surrogate in vivo assay system. Cells Tis-sues Organs 171:90–95, 2002.

    Google Scholar 

  44. Martin, R. B., D. B. Burr, and N. A. Sharkey. Skeletal Tissue Mechanics. New York: Springer-Verlag, 1998.

    Google Scholar 

  45. Mooney, D. J., and A. G. Mikos. Growing new organs. Science 280:60–65, 1999.

    Google Scholar 

  46. Naumann, A., J. E. Dennis, A. Awadallah, D. A. Carrino, J. M. Mansour, E. Kastenbauer, and A. I. Caplan. Immunochemical and mechanical characterization of cartilage subtypes in rabbit. J.Histochem.Cytochem. 50:1049–1058, 2002.

    Google Scholar 

  47. Nguyen, K. T., and J. L. West. Photopolymerizable hydrogels for tissue engineering applications. Biomaterials 23:4307–4314, 2002.

    Google Scholar 

  48. Patel, R. V., and J. J. Mao. Microstructural and elastic properties of the extracellular matrices of the superficial zone of neonatal articular cartilage by atomic force microscopy. Front.Biosci. 8:18–25, 2003.

    Google Scholar 

  49. Peacock, M., C. H. Turner, M. J. Econs, and T. Foroud. Genetics of osteoporosis. Endocr.Rev. 23:303–326, 2002.

    Google Scholar 

  50. Pei, M., L. A. Solchaga, J. Seidel, L. Zeng, G. Vunjak-Novakovic, A. I. Caplan, and L. E. Freed. Bioreactors mediate the effectiveness of tissue engineering scaffolds. FASEB J. 16:1691–1694, 2002.

    Google Scholar 

  51. Pelled, G., H. Aslan, Z. Gazit, and D. Gazit. Mesenchymal stem cells for bone gene therapy and tissue engineering. Curr.Pharm.Des. 8:1917–1928, 2002.

    Google Scholar 

  52. Pittenger, M. F., A. M. Mackay, S. C. Beck, R. K. Jaiswal, R. Douglas, J. D. Mosca, M. A. Moorman, D. W. Simonetti, S. Craig, and D. R. Marshak. Multilineage potential of adult human mesenchymal stem cells. Science 284:143–147, 1999.

    Google Scholar 

  53. Puelacher, W. C., J. Wisser, C. A. Vacanti, N. F. Ferraro, D. Jaramillo, and J. P. Vacanti. Temporomandibular joint disc re-placement made by tissue-engineered growth of cartilage. J.Oral Maxillofac.Surg. 52:1172–1177, 1994.

    Google Scholar 

  54. Roder, C., S. Eggli, M. Aebi, and A. Busato. The validity of clinical examination in the diagnosis of loosening of compo-nents in total hip arthroplasty. J.Bone Joint Surg.Br. 85:37–44, 2003.

    Google Scholar 

  55. Schaefer, D., I. Martin, G. Jundt, J. Seidel, M. Heberer, A. Grodzinsky, I. Bergin, G. Vunjak-Novakovic, and L. E. Freed. Tissue-engineered composites for the repair of large osteochondral defects. Arthritis Rheum. 46:2524–2534, 2002.

    Google Scholar 

  56. Schaefer, D., I. Martin, P. Shastri, R. F. Padera, R. Langer, L. E. Freed, and G. Vunjak-Novakovic. In vitro genera-tion of osteochondral composites. Biomaterials 21:2599–2606, 2000.

    Google Scholar 

  57. Sikavitsas, V. I., G. N. Bancroft, and A. G. Mikos. Formation of three-dimensional cell/polymer constructs for bone tissue engineering in a spinner flask and a rotating wall vessel bioreactor. J.Biomed.Mater.Res. 62:136–148, 2002.

    Google Scholar 

  58. Shum, L., and G. Nuckolls. The life cycle of chondrocytes in the developing skeleton. Arthritis Res. 4:94–106, 2002.

    Google Scholar 

  59. Solchaga, L. A., J. Gao, J. E. Dennis, A. Awadallah, M. Lundberg, A. I. Caplan, and V. M. Goldberg. Treatment of.Tissue-Engineered Articular Condyle 923 osteochondral defects with autologous bone marrow in a hyaluronan-based delivery vehicle. Tissue Eng. 8:333–347, 2002.

    Google Scholar 

  60. Tabata, Y., L. Hong, S. Miyamoto, M. Miyao, N. Hashimoto, and Y. Ikada. Bone formation at a rabbit skull defect by autol-ogous bone marrow cells combined with gelatin microspheres containing TGF-beta1. J.Biomater.Sci.Polym.Ed. 11:891–901, 2000.

    Google Scholar 

  61. Vacanti, C. A., W. Kim, B. Schloo, J. Upton, and J. P. Vacanti. Joint resurfacing with cartilage grown in situ from cell-polymer structures. Am.J.Sports Med. 22:485–488, 1994.

    Google Scholar 

  62. Vacanti, J. P., and R. Langer. Tissue engineering: The design and fabrication of living replacement devices for surgical reconstruction and transplantation. Lancet 354:132S–134S, 1999.

    Google Scholar 

  63. Wang, X., and J. J. Mao. Accelerated chondrogenesis of the rabbit cranial base growth plate upon oscillatory mechanical stimuli. J.Bone Miner.Res. 17:457–462, 2002.

    Google Scholar 

  64. Winn, S. R., J. M. Schmitt, D. Buck, Y. Hu, D. Grainger, and J. O. Hollinger. Tissue-engineered bone biomimetic to regenerate calvarial critical-sized defects in athymic rats. J.Biomed.Mater.Res. 45:414–421, 1999.

    Google Scholar 

  65. Zysset, P. K., X. E. Guo, C. E. Hoffler, K. E. Moore, and S. A. Goldstein. Elastic modulus and hardness of cortical and trabec-ular bone lamellae measured by nanoindentation in the human femur. J.Biomech. 32:1005–1012, 1999.

    Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Tissue Engineering Laboratory, Departments of Anatomy and Cell Biology, Bioengineering, and Orthodontics, University of Illinois at Chicago, Chicago, IL, USA

    Adel Alhadlaq, Liu Hong, Ross A. Kopher, Sara Tomkoria, Aurora Lopez & Jeremy J. Mao

  2. Departments of Biomedical Engineering and Plastic Surgery, Johns Hopkins University, Baltimore, MD, USA

    Jennifer H. Elisseeff, Christopher G. Williams & Blanka Sharma

  3. Skeletal Research Center, Department of Biology, Case Western Reserve University, Cleveland, OH, USA

    Arnold I. Caplan & Donald P. Lennon

Authors
  1. Adel Alhadlaq
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Jennifer H. Elisseeff
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Liu Hong
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Christopher G. Williams
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Arnold I. Caplan
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Blanka Sharma
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Ross A. Kopher
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Sara Tomkoria
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Donald P. Lennon
    View author publications

    You can also search for this author in PubMed Google Scholar

  10. Aurora Lopez
    View author publications

    You can also search for this author in PubMed Google Scholar

  11. Jeremy J. Mao
    View author publications

    You can also search for this author in PubMed Google Scholar

Rights and permissions

Reprints and permissions

About this article

Cite this article

Alhadlaq, A., Elisseeff, J.H., Hong, L. et al. Adult Stem Cell Driven Genesis of Human-Shaped Articular Condyle. Annals of Biomedical Engineering 32, 911–923 (2004). https://doi.org/10.1023/B:ABME.0000032454.53116.ee

Download citation

  • Issue Date:

  • DOI: https://doi.org/10.1023/B:ABME.0000032454.53116.ee

Search

Navigation