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Research Papers

Evolving Strategies in Mechanobiology to More Effectively Treat Damaged Musculoskeletal Tissues

[+] Author and Article Information
David L. Butler

Tissue Engineering and Biomechanics Laboratories,
Biomedical Engineering Program,
College of Engineering and Applied Sciences,
University of Cincinnati;
Cincinnati, OH 45221
e-mail: david.butler@uc.edu

Nathaniel A. Dyment

Department of Reconstructive Sciences,
College of Dental Medicine,
University of Connecticut Health Center,
Farmington, CT,
Farmington, CT 06030

Jason T. Shearn, Andrea L. Lalley

Tissue Engineering and Biomechanics Laboratories,
Biomedical Engineering Program,
College of Engineering and Applied Sciences,
University of Cincinnati,
Cincinnati, OH 45221

Kirsten R. C. Kinneberg

Department of Mechanical Engineering,
College of Engineering,
University of Colorado,
Boulder, CO 80309

Steven D. Gilday

Tissue Engineering and Biomechanics Laboratories,
Biomedical Engineering Program,
College of Engineering and Applied Sciences,
University of Cincinnati;
Medical Scientist Training Program,
College of Medicine,
University of Cincinnati,
Cincinnati, OH 45221

Cynthia Gooch

Tissue Engineering and Biomechanics Laboratories,
Biomedical Engineering Program,
College of Engineering and Applied Sciences,
University of Cincinnati,
Cincinnati, OH 45221

M. B. Rao

Department of Environmental Health,
College of Medicine,
University of Cincinnati,
Cincinnati, OH 45267

Christopher Wylie

Division of Developmental Biology,
Cincinnati Children's Hospital Medical Center,
Cincinnati, OH 45229

1Address Correspondence to: David L. Butler, Ph.D., Professor, Director, Tissue Engineering and Biomechanics Laboratories, Biomedical Engineering Program, College of Engineering and Applied Sciences, 601L Engineering Research Center, University of Cincinnati, 2901 Woodside Drive, Cincinnati, OH 45221-0048.

Contributed by the Bioengineering Division of ASME for publication in the JOURNAL OF BIOMECHANICAL ENGINEERING. Manuscript received October 10, 2012; final manuscript received January 15, 2013; accepted manuscript posted January 22, 2013; published online February 7, 2013. Editor: Victor H. Barocas.

J Biomech Eng 135(2), 021001 (Feb 07, 2013) (16 pages) Paper No: BIO-12-1475; doi: 10.1115/1.4023479 History: Received October 10, 2012; Revised January 15, 2013; Accepted January 22, 2013

In this paper, we had four primary objectives. (1) We reviewed a brief history of the Lissner award and the individual for whom it is named, H.R. Lissner. We examined the type (musculoskeletal, cardiovascular, and other) and scale (organism to molecular) of research performed by prior Lissner awardees using a hierarchical paradigm adopted at the 2007 Biomechanics Summit of the US National Committee on Biomechanics. (2) We compared the research conducted by the Lissner award winners working in the musculoskeletal (MS) field with the evolution of our MS research and showed similar trends in scale over the past 35 years. (3) We discussed our evolving mechanobiology strategies for treating musculoskeletal injuries by accounting for clinical, biomechanical, and biological considerations. These strategies included studies to determine the function of the anterior cruciate ligament and its graft replacements as well as novel methods to enhance soft tissue healing using tissue engineering, functional tissue engineering, and, more recently, fundamental tissue engineering approaches. (4) We concluded with thoughts about future directions, suggesting grand challenges still facing bioengineers as well as the immense opportunities for young investigators working in musculoskeletal research. Hopefully, these retrospective and prospective analyses will be useful as the ASME Bioengineering Division charts future research directions.

Copyright © 2013 by ASME
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Juncosa-Melvin, N., Boivin, G., Galloway, M., Gooch, C., West, J., Sklenka, A., and Butler, D., 2005, “Effects of Cell-to-Collagen Ratio in Mesenchymal Stem Cell-Seeded Implants on Tendon Repair Biomechanics and Histology,” Tissue Eng., 11(3-4), pp. 448–457. [CrossRef] [PubMed]
Dressler, M. R., Butler, D. L., and Boivin, G. P., 2005, “Effects of Age on the Repair Ability of Mesenchymal Stem Cells in Rabbit Tendon,” J. Orthop. Res., 23(2), pp. 287–293. [CrossRef] [PubMed]
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Juncosa-Melvin, N., Boivin, G. P., Gooch, C., Galloway, M. T., West, J. R., Dunn, M. G., and Butler, D. L., 2006, “The Effect of Autologous Mesenchymal Stem Cells on the Biomechanics and Histology of Gel-Collagen Sponge Constructs Used for Rabbit Patellar Tendon Repair,” Tissue Eng., 12(2), pp. 369–379. [CrossRef] [PubMed]
Juncosa-Melvin, N., Boivin, G., Galloway, M., Gooch, C., West, J., and Butler, D., 2006, “Effects of Cell-to-Collagen Ratio in Stem Cell-Seeded Constructs for Achilles Tendon Repair,” Tissue Eng., 12(4), pp. 681–689. [CrossRef] [PubMed]
Juncosa-Melvin, N., Shearn, J., Boivin, G., Gooch, C., Galloway, M., West, J., Nirmalanandhan, V., Bradica, G., and Butler, D., 2006, “Effects of Mechanical Stimulation on the Biomechanics and Histology of Stem Cell-Collagen Sponge Constructs for Rabbit Patellar Tendon Repair,” Tissue Eng., 12(8), pp. 2291–2300. [CrossRef] [PubMed]
Juncosa-Melvin, N., Matlin, K., Holdcraft, R., Nirmalanandhan, V., and Butler, D., 2007, “Mechanical Stimulation Increases Collagen Type I and Collagen Type III Gene Expression of Stem Cell-Collagen Sponge Constructs for Patellar Tendon Repair,” Tissue Eng., 13(6), pp. 1219–1226. [CrossRef] [PubMed]
Dressler, M. R., Butler, D. L., and Boivin, G. P., 2006, “Age-Related Changes in the Biomechanics of Healing Patellar Tendon,” J. Biomech., 39(12), pp. 2205–2212. [CrossRef] [PubMed]
Nirmalanandhan, V. S., Levy, M. S., Huth, A. J., and Butler, D. L., 2006, “Effects of Cell Seeding Density and Collagen Concentration on Contraction Kinetics of Mesenchymal Stem Cell-Seeded Collagen Constructs,” Tissue Eng., 12(7), pp. 1865–1872. [CrossRef] [PubMed]
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Nirmalanandhan, V., Shearn, J., Juncosa-Melvin, N., Rao, M., Gooch, C., Jain, A., Bradica, G., and Butler, D., 2008, “Improving Linear Stiffness of the Cell-Seeded Collagen Sponge Constructs by Varying the Components of the Mechanical Stimulus,” Tissue Eng., Part A, 14(11), pp. 1883–1891. [CrossRef]
Nirmalanandhan, V., Rao, M., Shearn, J., Juncosa-Melvin, N., Gooch, C., and Butler, D., 2008, “Effect of Scaffold Material, Construct Length and Mechanical Stimulation on the in vitro Stiffness of the Engineered Tendon Construct,” J. Biomech., 41(4), pp. 822–828. [CrossRef] [PubMed]
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Shearn, J. T., Juncosa-Melvin, N., Boivin, G. P., Galloway, M. T., Goodwin, W., Gooch, C., Dunn, M. G., and Butler, D. L., 2007, “Mechanical Stimulation of Tendon Tissue Engineered Constructs: Effects on Construct Stiffness, Repair Biomechanics, and Their Correlation,” ASME J. Biomech. Eng., 129(6), pp. 848–854. [CrossRef]
Butler, D., Juncosa-Melvin, N., Boivin, G., Galloway, M., Shearn, J., Gooch, C., and Awad, H., 2008, “Functional Tissue Engineering for Tendon Repair: A Multidisciplinary Strategy Using Mesenchymal Stem Cells, Bioscaffolds, and Mechanical Stimulation,” J. Orthop. Res., 26(1), pp. 1–9. [CrossRef] [PubMed]
FunctionalTissue Engineering Conference Group, 2008, “Evaluation Criteria for Musculoskeletal and Craniofacial Tissue Engineering Constructs: A Conference Report,” Tissue Eng., Part A, 14(12), pp. 2089–2104. [CrossRef]
Butler, D. L., Hunter, S. A., Chokalingam, K., Cordray, M. J., Shearn, J., Juncosa-Melvin, N., Nirmalanandhan, S., and Jain, A., 2009, “Using Functional Tissue Engineering and Bioreactors to Mechanically Stimulate Tissue-Engineered Constructs,” Tissue Eng., Part A, 15(4), pp. 741–749. [CrossRef]
Kinneberg, K. R. C., Nirmalanandhan, V. S., Juncosa-Melvin, N., Powell, H. M., Boyce, S. T., Shearn, J. T., and Butler, D. L., 2010, “Chondroitin-6-Sulfate Incorporation and Mechanical Stimulation Increase MSC-Collagen Sponge Construct Stiffness,” J. Orthop. Res., 28(8), pp. 1092–1099. [CrossRef] [PubMed]
Kinneberg, K. R. C., Galloway, M. T., Butler, D. L., and Shearn, J. T., 2011, “Effect of Implanting a Soft Tissue Autograft in a Central-Third Patellar Tendon Defect: Biomechanical and Histological Comparisons,” ASME J. Biomech. Eng., 133(9), p. 091002. [CrossRef]
Shearn, J. T., Kinneberg, K. R., Dyment, N. A., Galloway, M. T., Kenter, K., Wylie, C., and Butler, D. L., 2011, “Tendon Tissue Engineering: Progress, Challenges, and Translation to the Clinic,” J. Musculoskeletal and Neuronal Interact., 11(2), pp. 163–173.
Ingber, D., Mow, V., Butler, D., Niklason, L., Huard, J., Mao, J., Yannas, I., Kaplan, D., and Vunjak-Novakovic, G., 2006, “Tissue Engineering and Developmental Biology: Going Biomimetic,” Tissue Eng., 12(12), pp. 3265–3283. [CrossRef] [PubMed]
Chokalingam, K., Juncosa-Melvin, N., Hunter, S., Gooch, C., Frede, C., Florer, J., Bradica, G., Wenstrup, R., and Butler, D., 2009, “Tensile Stimulation of Murine Stem Cell-Collagen Sponge Constructs Increases Collagen Type I Gene Expression and Linear Stiffness,” Tissue Eng., Part A,15(9), pp. 2561–2570. [CrossRef]
Chokalingam, K., Hunter, S., Gooch, C., Frede, C., Florer, J., Wenstrup, R., and Butler, D., 2009, “Three-Dimensional in vitro Effects of Compression and Time in Culture on Aggregate Modulus and on Gene Expression and Protein Content of Collagen Type II in Murine Chondrocytes,” Tissue Eng., Part A, 15(10), pp. 2807–2816. [CrossRef]
Maye, P., Fu, Y., Butler, D. L., Chokalingam, K., Liu, Y., Florer, J., Stover, M. L., Wenstrup, R., Jiang, X., Gooch, C., and Rowe, D., 2011, “Generation and Characterization of Col10a1-mCherry Reporter Mice,” Genesis, 49(5), pp. 410–418. [CrossRef] [PubMed]
Liu, C., Aschbacher-Smith, L., Barthelery, N. J., Dyment, N., Butler, D., and Wylie, C., 2011, “What We Should Know Before Using Tissue Engineering Techniques to Repair Injured Tendons: A Developmental Biology Perspective,” Tissue Eng., Part B Rev., 17(3), pp. 165–176. [CrossRef]
Liu, C., Aschbacher-Smith, L., Bathelery, N. J., Dyment, N., Butler, D. L., and Wylie, C., 2012, “Spatial and Temporal Expression of Molecular Markers and Cell Signals During Normal Development of the Mouse Patellar Tendon,” Tissue Eng., Part A, 18(5-6), pp. 598–608. [CrossRef]
Dyment, N. A., Kazemi, N., Aschbacher-Smith, L. E., Barthelery, N. J., Kenter, K., Gooch, C., Shearn, J. T., Wylie, C., and Butler, D. L., 2011, “The Relationships Among Spatiotemporal Collagen Gene Expression, Histology, and Biomechanics Following Full-Length Injury in the Murine Patellar Tendon,” J. Orthop. Res., 30(1), pp. 28–36. [CrossRef] [PubMed]
Butler, D. L., Dyment, N. A., Shearn, J. T., Kinneberg, K. R. C., Breidenbach, A. P., Lalley, A. L., Gilday, S. D., Gooch, C., Liu, C., and Wylie, C., 2012, “Working Across Model Systems at the Interface Between Functional Tissue Engineering and Developmental Biology to Improve Adult Tendon Repair,” International Symposium of Ligaments and Tendons, San Francisco, CA.
Noyes, F. R., Bassett, R. W., Grood, E. S., and Butler, D. L., 1980, “Arthroscopy in Acute Traumatic Hemarthrosis of the Knee. Incidence of Anterior Cruciate Tears and Other Injuries,” J. Bone Jt. Surg. Am., 62(5), pp. 687–695, 757.
Praemer, A., Furner, S., and Rice, D. P., 1999, Musculoskeletal Condition in the United States, American Academy of Orthopaedic Surgeons, Park Ridge, IL, pp. 182.
Kleipool, A. E., Zijl, J. A., and Willems, W. J., 1998, “Arthroscopic Anterior Cruciate Ligament Reconstruction With Bone-Patellar Tendon-Bone Allograft or Autograft. A Prospective Study With an Average Follow Up of 4 Years,” Knee Surg. Sports Traumatol. Arthrosc., 6(4), pp. 224–230. [CrossRef] [PubMed]
Beasley, L. S., and Chudik, S. C., 2003, “Anterior Cruciate Ligament Injury in Children: Update of Current Treatment Options,” Curr. Opin. Pediatr., 15(1), pp. 45–52. [CrossRef] [PubMed]
Noyes, F. R., and Grood, E. S., 1976, “The Strength of the Anterior Cruciate Ligament in Humans and Rhesus Monkeys,” J. Bone Jt. Surg. Am., 58(8), pp. 1074–1082.
Ferretti, A., Conteduca, F., De Carli, A., Fontana, M., and Mariani, P. P., 1990, “Results of Reconstruction of the Anterior Cruciate Ligament With the Tendons of Semitendinosus and Gracilis in Acute Capsulo-Ligamentous Lesions of the Knee,” Ital. J. Orthop. Traumatol., 16(4), pp. 452–458. [PubMed]
Hanley, P., Lew, W. D., Lewis, J. L., Hunter, R. E., Kirstukas, S., and Kowalczyk, C., 1989, “Load Sharing and Graft Forces in Anterior Cruciate Ligament Reconstructions With the Ligament Augmentation Device,” Am. J. Sports Med., 17(3), pp. 414–422. [CrossRef] [PubMed]
Engebretsen, L., Lew, W. D., Lewis, J. L., and Hunter, R. E., 1990, “The Effect of an Iliotibial Tenodesis on Intraarticular Graft Forces and Knee Joint Motion,” Am. J. Sports Med., 18(2), pp. 169–176. [CrossRef] [PubMed]
Tibone, J. E., and Antich, T. J., 1988, “A Biomechanical Analysis of Anterior Cruciate Ligament Reconstruction With the Patellar Tendon. A Two Year Follow-Up,” Am. J. Sports Med., 16(4), pp. 332–335. [CrossRef] [PubMed]
Yasuda, K., Tomiyama, Y., Ohkoshi, Y., and Kaneda, K., 1989, “Arthroscopic Observations of Autogeneic Quadriceps and Patellar Tendon Grafts After Anterior Cruciate Ligament Reconstruction of the Knee,” Clin. Orthop. Relat. Res., 246, pp. 217–224. [CrossRef] [PubMed]
Race, A., and Amis, A. A., 1994, “The Mechanical Properties of the Two Bundles of the Human Posterior Cruciate Ligament,” J. Biomech., 27(1), pp. 13–24. [CrossRef] [PubMed]
Yamamoto, N., Ohno, K., Hayashi, K., Kuriyama, H., Yasuda, K., and Kaneda, K., 1993, “Effects of Stress Shielding on the Mechanical Properties of Rabbit Patellar Tendon,” ASME J. Biomech. Eng, 115(1), pp. 23–28. [CrossRef]
Xu, W. S., Butler, D. L., Stouffer, D. C., Grood, E. S., and Glos, D. L., 1992, “Theoretical Analysis of an Implantable Force Transducer for Tendon and Ligament Structures,” ASME J. Biomech. Eng., 114(2), pp. 170–177. [CrossRef]
Glos, D. L., Butler, D. L., Grood, E. S., and Levy, M. S., 1993, “In vitro Evaluation of an Implantable Force Transducer (IFT) in a Patellar Tendon Model,” ASME J. Biomech. Eng., 115(4A), pp. 335–343. [CrossRef]
Holden, J. P., Grood, E. S., Korvick, D. L., Cummings, J. F., Butler, D. L., and Bylski-Austrow, D. I., 1994, “In vivo Forces in the Anterior Cruciate Ligament: Direct Measurements During Walking and Trotting in a Quadruped,” J. Biomech., 27(5), pp. 517–526. [CrossRef] [PubMed]
Myers, R. L., Montgomery, D. C., and Anderson-Cook, C., 2009, Response Surface Methodology: Process and Product Optimization Using Designed Experiments, Wiley, Hoboken, NJ, p. 704.
Hunziker, E., Spector, M., Libera, J., Gertzman, A., Woo, S. L., Ratcliffe, A., Lysaght, M., Coury, A., Kaplan, D., and Vunjak-Novakovic, G., 2006, “Translation From Research to Applications,” Tissue Eng., 12(12), pp. 3341–3364. [CrossRef] [PubMed]
Stouffer, D. C., Butler, D. L., and Kim, H., 1983, “Tension-Torsion Characteristics of the Canine Anterior Cruciate Ligament–Part I: Theoretical Framework,” ASME J. Biomech. Eng., 105(2), pp. 154–159. [CrossRef]
Butler, D. L., Hulse, D. A., Kay, M. D., Grood, E. S., Shires, P. K., D'Ambrosia, R., and Shoji, H., 1983, “Biomechanics of Cranial Cruciate Reconstruction in the Dog: II. Mechanical Properties,” Vet. Surg., 12, pp. 113–118. [CrossRef]
Butler, D. L., and Stouffer, D. C., 1983, “Tension-Torsion Characteristics of the Canine Anterior Cruciate Ligament–Part II: Experimental Observations,” ASME J. Biomech. Eng., 105(2), pp. 160–165. [CrossRef]
Hulse, D. A., Butler, D. L., Kay, M. D., Noyes, F. R., Shires, P. K., D'Ambrosia, R., and Shoji, H., 1983, “Biomechanics of Cranial Cruciate Reconstruction in the Dog: I. in vitro Laxity Testing,” Vet. Surg., 12, pp. 109–112. [CrossRef]
Jackson, D. W., Grood, E. S., Arnoczky, S. P., Butler, D. L., and Simon, T. M., 1987, “Freeze Dried Anterior Cruciate Ligament Allografts. Preliminary Studies in a Goat Model,” Am. J. Sports Med., 15(4), pp. 295–303. [CrossRef] [PubMed]
Jackson, D. W., Grood, E. S., Arnoczky, S. P., Butler, D. L., and Simon, T. M., 1987, “Cruciate Reconstruction Using Freeze Dried Anterior Cruciate Ligament Allograft and a Ligament Augmentation Device (LAD). An Experimental Study in a Goat Model,” Am. J. Sports Med., 15(6), pp. 528–538. [CrossRef] [PubMed]
Jackson, D. W., Grood, E. S., Wilcox, P., Butler, D. L., Simon, T. M., and Holden, J. P., 1988, “The Effects of Processing Techniques on the Mechanical Properties of Bone-Anterior Cruciate Ligament-Bone Allografts. An Experimental Study in Goats,” Am. J. Sports Med., 16(2), pp. 101–105. [CrossRef] [PubMed]
Byrne, E. M., Farrell, E., McMahon, L. A., Haugh, M. G., O'Brien, F. J., Campbell, V. A., Prendergast, P. J., and O'Connell, B. C., 2008, “Gene Expression by Marrow Stromal Cells in a Porous Collagen-Glycosaminoglycan Scaffold Is Affected by Pore Size and Mechanical Stimulation,” J. Mater. Sci. Mater. Med., 19(11), pp. 3455–3463. [CrossRef] [PubMed]
Lysaght, M. J., and Crager, J., 2009, “Origins,” Tissue Eng., Part A, 15(7), pp. 1449–1450. [CrossRef]
Herfat, S. T., Shearn, J. T., Bailey, D. L., Greiwe, R. M., Galloway, M. T., Gooch, C., and Butler, D. L., 2011, “Effect of Surgery to Implant Motion and Force Sensors on Vertical Ground Reaction Forces in the Ovine Model,” ASME J. Biomech. Eng., 133(2), p. 021010. [CrossRef]
Howard, R., Rosvold, J. M., and Tapper, J. E., 2004, “Measurement of Loads in the Ovine Stifle Joint During in vitro Robotic Reproduction of in vivo Kinematics,” Transactions of the 2004 International Symposium on Ligaments and Tendons.
Howard, R. A., Rosvold, J. M., Darcy, S. P., Corr, D. T., Shrive, N. G., Tapper, J. E., Ronsky, J. L., Beveridge, J. E., Marchuk, L. L., and Frank, C. B., 2007, “Reproduction of in vivo Motion Using a Parallel Robot,” ASME J. Biomech. Eng., 129(5), pp. 743–749. [CrossRef]
Boguszewski, D. V., Shearn, J. T., Wagner, C. T., and Butler, D. L., 2011, “Investigating the Effects of Anterior Tibial Translation on Anterior Knee Force in the Porcine Model: Is the Porcine Knee ACL Dependent?” J. Orthop. Res., 29(5), pp. 641–646. [CrossRef] [PubMed]
Nesbitt, R. J., Herfat, S. T., Galloway, M. T., Gooch, C., Butler, D. L., and Shearn, J. T., 2012, “Effects of Altering Grade on Vertical Ground Reaction Forces and ACL Forces in the Sheep Model,” Transaction of the International Symposium on Ligaments and Tendons - XII, San Francisco, CA.
Tashman, S., Kolowich, P., Collon, D., Anderson, K., and Anderst, W., 2007, “Dynamic Function of the ACL-Reconstructed Knee During Running,” Clin. Orthop. Relat. Res., 454, pp. 66–73. [CrossRef] [PubMed]
Li, G., Rudy, T. W., Sakane, M., Kanamori, A., Ma, C. B., and Woo, S. L., 1999, “The Importance of Quadriceps and Hamstring Muscle Loading on Knee Kinematics and In-Situ Forces in the ACL,” J. Biomech., 32(4), pp. 395–400. [CrossRef] [PubMed]
Li, G., Zayontz, S., Most, E., DeFrate, L. E., Suggs, J. F., and Rubash, H. E., 2004, “In Situ Forces of the Anterior and Posterior Cruciate Ligaments in High Knee Flexion: An in vitro Investigation,” J. Orthop. Res., 22(2), pp. 293–297. [CrossRef] [PubMed]
Kanamori, A., Woo, S. L., Ma, C. B., Zeminski, J., Rudy, T. W., Li, G., and Livesay, G. A., 2000, “The Forces in the Anterior Cruciate Ligament and Knee Kinematics During a Simulated Pivot Shift Test: A Human Cadaveric Study Using Robotic Technology,” Arthroscopy, 16(6), pp. 633–639. [CrossRef] [PubMed]
Shin, C. S., Chaudhari, A. M., and Andriacchi, T. P., 2009, “The Effect of Isolated Valgus Moments on ACL Strain During Single-Leg Landing: A Simulation Study,” J. Biomech., 42(3), pp. 280–285. [CrossRef] [PubMed]
Kinney, A. L., Besier, T. F., Silder, A., Delp, S. L., D'Lima, D. D., and Fregly, B. J., “Changes in in vivo Knee Contact Forces Through Gait Modification,” J. Orthop. Res., (in press).
Kutzner, I., Heinlein, B., Graichen, F., Bender, A., Rohlmann, A., Halder, A., Beier, A., and Bergmann, G., 2010, “Loading of the Knee Joint During Activities of Daily Living Measured in vivo in Five Subjects,” J. Biomech., 43(11), pp. 2164–2173. [CrossRef] [PubMed]
Georgoulis, A. D., Papadonikolakis, A., Papageorgiou, C. D., Mitsou, A., and Stergiou, N., 2003, “Three-Dimensional Tibiofemoral Kinematics of the Anterior Cruciate Ligament-Deficient and Reconstructed Knee During Walking,” Am. J. Sports Med., 31(1), pp. 75–79. [PubMed]
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Benoit, D. L., Ramsey, D. K., Lamontagne, M., Xu, L., Wretenberg, P., and Renstrom, P., 2006, “Effect of Skin Movement Artifact on Knee Kinematics During Gait and Cutting Motions Measured in vivo,” Gait and Posture, 24(2), pp. 152–164. [CrossRef] [PubMed]

Figures

Grahic Jump Location
Fig. 1

(a)–(d) Prior Lissner Award winners assigned to four 9-year phases between 1977 and 2012

Grahic Jump Location
Fig. 2

An analysis of cardiovascular versus musculoskeletal research between 1977 and 2011. (a) Primary and secondary research areas for Lissner awardees working in the cardiovascular area mostly remained at the tissue and cell level during the four 9-year phases. (b) By contrast, primary and secondary areas for Lissner winners working in the musculoskeletal area moved from the organism/organ level to the tissue/cell level around 1998 (p = 0.05). Also interesting to note from PubMed is that, during this same period, (c) the number of cardiovascular publications far exceeded those in the musculoskeletal field (e.g., 50,355 versus 3152 in 2011). (d) Despite this discrepancy, when this data was restricted to biomechanics publications, the two groups were much more similar and began to converge in the late 1990 s.

Grahic Jump Location
Fig. 3

The ACL (bottom graph) is the primary ligamentous restraint up to 5 mm of anterior tibial translation (85% of total anterior restraining force). The PCL (middle graph) is the primary restraint up to 5 mm of posterior tibial translation (94%–96% of total restraining force). Adapted with permission from Ref. [9].

Grahic Jump Location
Fig. 4

Anterior knee laxity versus activity forces in intact cadaveric knee and after individual sectioning of the ACL and PCL. The surgeon may not detect a small increase in anterior laxity in the ACL-deficient knee under “light” forces of the clinical exam, but the patient definitely experiences the greater increases in laxity under more strenuous forces. The increases in posterior laxity after loss of the PCL are more pronounced at both load levels. Adapted with permission from Ref. [9].

Grahic Jump Location
Fig. 5

Maximum forces generated by graft tissues compared to the young adult anterior cruciate ligament-bone unit. Central- and medial bone-patellar tendon-bone units were the strongest tissues (159%–168% of ACL failure force). The semitendinosis (70%) and gracilis (49%) tendons were somewhat weaker than the ACL. All other structures were still weaker, with the retinacular tissues transmitting only 14%–21% of ACL maximum force. Adapted with permission from Ref. [12].

Grahic Jump Location
Fig. 6

Designing a graft to withstand normal ligament failure forces is ideal. However, designing grafts within “safety zones” for normal and strenuous ADLs might matter more. Unfortunately, researchers in the mid-1980s could only estimate these force limits. Adapted with permission from Ref. [12].

Grahic Jump Location
Fig. 7

Unloading the rabbit PT with K-wire and sutures produced 70%–80% reductions in tissue material properties by 6 weeks postsurgery. Adapted with permission from Ref. [94].

Grahic Jump Location
Fig. 8

Peak in vivo forces in the patellar tendon are larger than those in the anterior cruciate ligament. (a) Note that peak IVFs in the goat ACL are negligible during the swing phase of gait, increasing rapidly during stance but never exceeding 7%–10% of the tissue's failure force. (b) Peak PT force is 8% of failure force during stance phase, increasing rapidly during gait to 32%–40% of failure force at 2.0–2.5 m/s. Adapted with permission from Refs. [97] and [33].

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Fig. 9

Functional design limits for the goat anterior cruciate ligament were found to be less than those for the goat patellar tendon. Adapted with permission from Ref. [12].

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Fig. 10

Functional tissue engineering roadmap. Shown are the in vitro, tissue engineering phase required to create a tissue engineering substitute or construct as well as the important surgery and evaluation phase to determine if the repair regenerates the tissue to exceed in vivo forces or at least repairs to achieve functional efficacy. Adapted from Ref. [47].

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Fig. 11

Continuous improvement in traditional biomechanical properties, including maximum force, stiffness, maximum stress, and linear modulus. These improvements involved changes in cell density, collagen scaffold stiffness, and the use of mechanical preconditioning of the TEC before surgery. Adapted from Ref. [69].

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Fig. 12

Tissue-engineered constructs containing MSCs in a collagen scaffold improve central rabbit PT repair. (a) Constructs containing a high cell density (1 × 106 cells/ml) produce a small but significant improvement in the force-displacement repair curve compared to natural healing. Not only does the failure curve for the TEC repair not match that for the normal unoperated PT, the 12-week repair also does not reach the peak in vivo forces (IVFs) acting on the normal central PT or match normal tangent stiffness. (b) Lowering the cell density, stiffening the collagen scaffold, and mechanically preconditioning the constructs before surgery resulted in improvements in failure properties as well as functional parameters (exceeding peak IVFs and matching normal PT tangent stiffness with a 50% safety factor). Adapted from Ref. [56].

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Fig. 13

The murine patellar tendon rapidly changes its structure and cellularity from late fetal life to 2 weeks after birth. The tendon midsubstance and insertion are cellular and their extracellular matrices are rather poorly aligned at E17.5. Postnatally, the tissue midsubstance shows decreasing cellularity and increasing collagen alignment from P1 to P14. The insertion is also maturing into fibrocartilage and bone. Adapted with permission from Ref. [80].

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Fig. 14

Natural healing of murine central patellar tendon defect injury. (a) Healing occurs slowly between 2 and 8 weeks postinjury when compared to the normal tendon failure curve. Estimated upper and lower peak in vivo force bounds are shown (using rabbit results from Ref. [37] and goat results from Ref. [33]) (from Ref. [81]). (b) Panels of genes for normal, sham, and defect healing groups at 1, 2, and 3 weeks postsurgery analyzed using principal component analysis.

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Fig. 15

A fundamental tissue engineering strategy that seeks to more rapidly design, evaluate, and optimize tissue-engineered constructs using normal tissue development, natural healing, and TEC manipulation across species. Adapted from Ref. [82].

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Fig. 16

Tendon healing shares similar characteristics with bone healing. Central PT healing in the mouse (upper panel, cross-sectional view) results in paratenon progenitor cells proliferating and migrating to form a bridge over the anterior surface of the defect space. This response is similar to fracture callus formation in tibial fractures (lower panel). Scleraxis (Scx) GFP reporter expression and smooth muscle actin α (SMAA) immunostaining (red) label potential early progenitor cells in these healing scenarios. White arrows indicate coexpressing cells.

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