The incidence of ligament injury has recently been estimated at 400,000/year. The preferred treatment is reconstruction using an allograft, but outcomes are limited by donor availability, biomechanical incompatibility, and immune rejection. The creation of an engineered ligament in vitro solely from patient bone marrow stromal cells (has the potential to greatly enhance outcomes in knee reconstructions. Our laboratory has developed a scaffoldless method to engineer three-dimensional (3D) ligament and bone constructs from rat bone marrow stem cells in vitro. Coculture of these two engineered constructs results in a 3D bone-ligament-bone (BLB) construct with viable entheses, which was successfully used for medial collateral ligament (MCL) replacement in a rat model. 1 month and 2 month implantations were applied to the engineered BLBs. Implantation of 3D BLBs in a MCL replacement application demonstrated that our in vitro engineered tissues grew and remodeled quickly in vivo to an advanced phenotype and partially restored function of the knee. The explanted 3D BLB ligament region stained positively for type I collagen and elastin and was well vascularized after 1 and 2 months in vivo. Tangent moduli of the ligament portion of the 3D BLB 1 month explants increased by a factor of 2.4 over in vitro controls, to a value equivalent to those observed in 14-day-old neonatal rat MCLs. The 3D BLB 1 month explants also exhibited a functionally graded response that closely matched native MCL inhomogeneity, indicating the constructs functionally adapted in vivo.
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e-mail: arruda@umich.edu
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October 2009
Research Papers
Morphological and Functional Characteristics of Three-Dimensional Engineered Bone-Ligament-Bone Constructs Following Implantation
Jinjin Ma,
Jinjin Ma
Department of Mechanical Engineering,
University of Michigan
, Ann Arbor, MI 48109
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Kristen Goble,
Kristen Goble
Department of Molecular and Integrative Physiology,
University of Michigan, Ann Arbor, MI 48109
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Michael Smietana,
Michael Smietana
Department of Biomedical Engineering,
University of Michigan
, Ann Arbor, MI 48109
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Tatiana Kostrominova,
Tatiana Kostrominova
Department of Anatomy and Cell Biology,
Indiana University School of Medicine-Northwest
, Gary, IN 46409-1008
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Lisa Larkin,
Lisa Larkin
Department of Biomedical Engineering, and Department of Molecular and Integrative Physiology,
University of Michigan
, Ann Arbor, MI 48109
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Ellen M. Arruda
Ellen M. Arruda
Fellow ASME
Department of Mechanical Engineering,
e-mail: arruda@umich.edu
University of Michigan
, Ann Arbor, MI 48109; Macromolecular Science and Engineering Program, University of Michigan
, Ann Arbor, MI 48109
Search for other works by this author on:
Jinjin Ma
Department of Mechanical Engineering,
University of Michigan
, Ann Arbor, MI 48109
Kristen Goble
Department of Molecular and Integrative Physiology,
University of Michigan, Ann Arbor, MI 48109
Michael Smietana
Department of Biomedical Engineering,
University of Michigan
, Ann Arbor, MI 48109
Tatiana Kostrominova
Department of Anatomy and Cell Biology,
Indiana University School of Medicine-Northwest
, Gary, IN 46409-1008
Lisa Larkin
Department of Biomedical Engineering, and Department of Molecular and Integrative Physiology,
University of Michigan
, Ann Arbor, MI 48109
Ellen M. Arruda
Fellow ASME
Department of Mechanical Engineering,
University of Michigan
, Ann Arbor, MI 48109; Macromolecular Science and Engineering Program, University of Michigan
, Ann Arbor, MI 48109e-mail: arruda@umich.edu
J Biomech Eng. Oct 2009, 131(10): 101017 (9 pages)
Published Online: October 13, 2009
Article history
Received:
November 15, 2008
Revised:
August 4, 2009
Posted:
September 3, 2009
Published:
October 13, 2009
Citation
Ma, J., Goble, K., Smietana, M., Kostrominova, T., Larkin, L., and Arruda, E. M. (October 13, 2009). "Morphological and Functional Characteristics of Three-Dimensional Engineered Bone-Ligament-Bone Constructs Following Implantation." ASME. J Biomech Eng. October 2009; 131(10): 101017. https://doi.org/10.1115/1.4000151
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