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RESEARCH PAPERS

Mechanical Stimulation of Tendon Tissue Engineered Constructs: Effects on Construct Stiffness, Repair Biomechanics, and Their Correlation

[+] Author and Article Information
Jason T. Shearn1

Tissue Engineering and Biomechanics Laboratories, Department of Biomedical Engineering, University of Cincinnati, Mail Location 0048, Cincinnati, OH 45221-0048shearnj@email.uc.edu

Natalia Juncosa-Melvin

Tissue Engineering and Biomechanics Laboratories, Department of Biomedical Engineering, University of Cincinnati, Mail Location 0048, Cincinnati, OH 45221-0048juncosln@email.uc.edu

Gregory P. Boivin

 Veterans Affairs Medical Center, Cincinnati, Ohio 45220; Department of Pathology and Laboratory Medicine, University of Cincinnati, Mail Location 0529, Cincinnati, OH 45267-0529boivingp@email.uc.edu

Marc T. Galloway

 Cincinnati Sports Medicine and Orthopaedic Center, 12115 Sheraton Lane, Cincinnati, OH 45249mtgalloway@aol.com

Wendy Goodwin

Tissue Engineering and Biomechanics Laboratories, Department of Biomedical Engineering, University of Cincinnati, Mail Location 0048, Cincinnati, OH 45221-0048goodwiwg@email.uc.edu

Cynthia Gooch

Tissue Engineering and Biomechanics Laboratories, Department of Biomedical Engineering, University of Cincinnati, Mail Location 0048, Cincinnati, OH 45221-0048goochc@uc.edu

Michael G. Dunn

 Robert Wood Johnson Medical Center, Department of Orthopedic Surgery, P.O. Box 19, New Brunswick, NJ 08903-0019dunnmg@umdnj.edu

David L. Butler

Tissue Engineering and Biomechanics Laboratories, Department of Biomedical Engineering, University of Cincinnati, Mail Location 0048, Cincinnati, OH 45221-0048david.butler@uc.edu

1

Corresponding author.

J Biomech Eng 129(6), 848-854 (Mar 13, 2007) (7 pages) doi:10.1115/1.2800769 History: Received May 26, 2006; Revised March 13, 2007

The objective of this study was to determine how in vitro mechanical stimulation of tissue engineered constructs affects their stiffness and modulus in culture and tendon repair biomechanics 12weeks after surgical implantation. Using six female adult New Zealand White rabbits, autogenous tissue engineered constructs were created by seeding mesenchymal stem cells (0.1×106cellsml) in collagen gel (2.6mgml) and combining both with a collagen sponge. Employing a novel experimental design strategy, four constructs from each animal were mechanically stimulated (one 1Hzcycle every 5min to 2.4% peak strain for 8hday for 2weeks) while the other four remained unstretched during the 2week culture period. At the end of incubation, three of the mechanically stimulated (S) and three of the nonstimulated (NS) constructs from each animal were assigned for in vitro mechanical testing while the other two autogenous constructs were implanted into bilateral full-thickness, full-length defects created in the central third of rabbit patellar tendons (PTs). No significant differences were found in the in vitro linear stiffnesses between the S (0.15±0.1Nmm) and NS constructs (0.08±0.02Nmm; mean±SD). However, in vitro mechanical stimulation significantly increased the structural and material properties of the repair tissue, including a 14% increase in maximum force (p=0.01), a 50% increase in linear stiffness (p=0.001), and 23–41% increases in maximum stress and modulus (p=0.01). The S repairs achieved 65%, 80%, 60%, and 40% of normal central PT maximum force, linear stiffness, maximum stress, and linear modulus, respectively. The results for the S constructs exceed values obtained previously by our group using the same animal and defect model, and to our knowledge, this is the first study to show the benefits of in vitro mechanical stimulation on tendon repair biomechanics. In addition, the linear stiffnesses for the construct and repair were positively correlated (r=0.56) as were their linear moduli (r=0.68). Such in vitro predictors of in vivo outcome hold the potential to speed the development of tissue engineered products by reducing the time and costs of in vivo studies.

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Copyright © 2007 by American Society of Mechanical Engineers
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Figures

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Figure 1

Mechanical stimulation system showing four stations in the incubator. Each station contains a silicone dish, a pneumatic cylinder to stretch the dish, and a LVDT to monitor the end-to-end displacement of the dish.

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Figure 2

Force versus displacement curves (mean±SD) for the nonstimulated (NS; n=6) and stimulated constructs (S; n=6) at 14days in culture

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Figure 3

Average (mean±SD) force versus displacement curves for the normal PT (N; n=8), stimulated (S; n=6), and nonstimulated PT repairs (NS; n=6) at 12weeks after surgery. The curve includes peak in vivo force (IVF) and in vivo displacement (IVD) thresholds for inclined hopping, the most vigorous activity examined in a normal rabbit (18).

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Figure 4

(a) Correlation between construct linear stiffness at 14days in culture and repair linear stiffness at 12weeks after surgery (r=0.56). (b) Correlation between construct linear modulus at 14days in culture and repair linear modulus at 12weeks after surgery (r=0.68).

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