Hostname: page-component-78c5997874-8bhkd Total loading time: 0 Render date: 2024-11-09T02:26:10.576Z Has data issue: false hasContentIssue false
  • English
  • Français

Quantification of Collagen Organization and Extracellular Matrix Factors within the Healing Ligament

Published online by Cambridge University Press:  13 September 2011

Connie S. Chamberlain ,
Erin M. Crowley ,
Hirohito Kobayashi ,
Kevin W. Eliceiri  and
Ray Vanderby
Connie S. Chamberlain
Affiliation:
Department of Orthopedics and Rehabilitation, University of Wisconsin, Madison, WI 53705, USA
Erin M. Crowley
Affiliation:
Department of Orthopedics and Rehabilitation, University of Wisconsin, Madison, WI 53705, USA
Hirohito Kobayashi
Affiliation:
Department of Orthopedics and Rehabilitation, University of Wisconsin, Madison, WI 53705, USA
Kevin W. Eliceiri
Affiliation:
Laboratory for Optical and Computational Instrumentation, University of Wisconsin, Madison, WI 53705, USA Department of Biomedical Engineering, University of Wisconsin, Madison, WI 53705, USA
Ray Vanderby*
Affiliation:
Department of Orthopedics and Rehabilitation, University of Wisconsin, Madison, WI 53705, USA Department of Biomedical Engineering, University of Wisconsin, Madison, WI 53705, USA
*
Corresponding author. E-mail: vanderby@ortho.wisc.edu
Get access

Abstract

Ligament healing of a grade III injury (i.e., a complete tear) involves a multifaceted chain of events that forms a neoligament, which is more scar-like in character than the native tissue. The remodeling process may last months or even years with the injured ligament never fully recovering pre-injury mechanical properties. With tissue engineering and regenerative medicine, understanding the normal healing process in ligament and quantifying it provide a basis to create and assess innovative treatments. Ligament fibroblasts produce a number of extracellular matrix (ECM) components, including collagen types I and III, decorin and fibromodulin. Using a combination of advanced histology, molecular biology, and nonlinear optical imaging approaches, the early ECM events during ligament healing have been better characterized and defined. First, the dynamic changes in ECM factors after injury are shown. Second, the factors associated with creeping substitution are identified. Finally, a method to quantify collagen organization is developed and used. Each ECM factor described herein as well as the temporal quantification of fiber organization helps elucidate the complexity of ligament healing.

Keywords

ligamentmultiphoton microscopyhealingcollagentissue engineering
Type
Biological Applications
Information
Microscopy and Microanalysis , Volume 17 , Issue 5 , October 2011 , pp. 779 - 787
Copyright
Copyright © Microscopy Society of America 2011

Access options

Get access to the full version of this content by using one of the access options below. (Log in options will check for institutional or personal access. Content may require purchase if you do not have access.)

References

REFERENCES

Bashford, G.R., Tomsen, N., Arya, S., Burnfield, J.M. & Kulig, K. (2008). Tendinopathy discrimination by use of spatial frequency parameters in ultrasound B-mode images. IEEE Trans Med Imaging 27(5), 608–615.CrossRefGoogle ScholarPubMed
Brown, D.C. & Vogel, K.G. (1989). Characteristics of the in vitro interaction of a small proteoglycan (PG II) of bovine tendon with type I collagen. Matrix (Stuttgart, Germany) 9(6), 468–478.Google ScholarPubMed
Centonze, V.E. & White, J.G. (1998). Multiphoton excitation provides optical sections from deeper within scattering specimens than confocal imaging. Biophys J 75(4), 2015–2024.CrossRefGoogle ScholarPubMed
Chamberlain, C.S., Crowley, E. & Vanderby, R. (2009). The spatio-temporal dynamics of ligament healing. Wound Repair Regen 17(2), 206–215.CrossRefGoogle ScholarPubMed
Dagher, E., Hays, P.L., Kawamura, S., Godin, J., Deng, X.H. & Rodeo, S.A. (2009). Immobilization modulates macrophage accumulation in tendon-bone healing. Clin Orthop Relat Res 467(1), 281–287.CrossRefGoogle ScholarPubMed
Danielson, K.G., Baribault, H., Holmes, D.F., Graham, H., Kadler, K.E. & Iozzo, R.V. (1997). Targeted disruption of decorin leads to abnormal collagen fibril morphology and skin fragility. J Cell Biol 136(3), 729–743.CrossRefGoogle ScholarPubMed
Denk, W., Strickler, J.H. & Webb, W.W. (1990). Two-photon laser scanning fluorescence microscopy. Science 248(4951), 73–76.CrossRefGoogle ScholarPubMed
Desmouliere, A., Chaponnier, C. & Gabbiani, G. (2005). Tissue repair, contraction, and the myofibroblast. Wound Repair Regen 13(1), 7–12.CrossRefGoogle ScholarPubMed
Gray, S.D., Titze, I.R., Chan, R. & Hammond, T.H. (1999). Vocal fold proteoglycans and their influence on biomechanics. Laryngoscope 109(6), 845–854.CrossRefGoogle ScholarPubMed
Hedbom, E. & Heinegard, D. (1989). Interaction of a 59-kDa connective tissue matrix protein with collagen I and collagen II. J Biol Chem 264(12), 6898–6905.CrossRefGoogle ScholarPubMed
Iozzo, R.V. (1999). The biology of the small leucine-rich proteoglycans. Functional network of interactive proteins. J Biol Chem 274(27), 18843–18846.CrossRefGoogle ScholarPubMed
Jepsen, K.J., Wu, F., Peragallo, J.H., Paul, J., Roberts, L., Ezura, Y., Oldberg, A., Birk, D.E. & Chakravarti, S. (2002). A syndrome of joint laxity and impaired tendon integrity in lumican- and fibromodulin-deficient mice. J Biol Chem 277(38), 35532–35540.CrossRefGoogle ScholarPubMed
Lacomb, R., Nadiarnykh, O. & Campagnola, P.J. (2008). Quantitative second harmonic generation imaging of the diseased state osteogenesis imperfecta: Experiment and simulation. Biophys J 94(11), 4504–4514.CrossRefGoogle ScholarPubMed
Levenson, S.M., Geever, E.F., Crowley, L.V., Oates, J.F. 3rd, Berard, C.W. & Rosen, H. (1965). The healing of rat skin wounds. Ann Surg 161, 293–308.CrossRefGoogle ScholarPubMed
Lin, T.W., Cardenas, L. & Soslowsky, L.J. (2004). Biomechanics of tendon injury and repair. J Biomech 37(6), 865–877.CrossRefGoogle ScholarPubMed
Marsolais, D., Cote, C.H. & Frenette, J. (2001). Neutrophils and macrophages accumulate sequentially following Achilles tendon injury. J Orthop Res 19(6), 1203–1209.CrossRefGoogle ScholarPubMed
Masters, B.R. (2009). Correlation of histology and linear and nonlinear microscopy of the living human cornea. J Biophotonics 2(3), 127–139.CrossRefGoogle ScholarPubMed
Matheson, S., Larjava, H. & Hakkinen, L. (2005). Distinctive localization and function for lumican, fibromodulin and decorin to regulate collagen fibril organization in periodontal tissues. J Periodontal Res 40(4), 312–324.CrossRefGoogle ScholarPubMed
Nordin, M., Lorenz, T. & Campello, M. (2001). Biomechanics of tendons and ligament. In Basic Biomechanics of the Musculoskeletal System, Nordine, M. & Frankel, V.H. (Eds.), pp. 103–125. Philadelphia, PA: Lippincott Williams and Wilkins.Google Scholar
Provenzano, P.P., Alejandro-Osorio, A.L., Valhmu, W.B., Jensen, K.T. & Vanderby, R. Jr. (2005). Intrinsic fibroblast-mediated remodeling of damaged collagenous matrices in vivo. Matrix Biol 23(8), 543–555.CrossRefGoogle ScholarPubMed
Provenzano, P.P., Rueden, C.T., Trier, S.M., Yan, L., Ponik, S.M., Inman, D.R., Keely, P.J. & Eliceiri, K.W. (2008). Nonlinear optical imaging and spectral-lifetime computational analysis of endogenous and exogenous fluorophores in breast cancer. J Biomed Optics 13(3), 031220.CrossRefGoogle ScholarPubMed
Qian, H., Xiao, Y. & Bartold, P.M. (2004). Immunohistochemical localization and expression of fibromodulin in adult rat periodontium and inflamed human gingiva. Oral Dis 10(4), 233–239.CrossRefGoogle ScholarPubMed
R Development Core Team (2006, last update). A language and environment for statistical computing. Available at http://www.R-project.org.Google Scholar
Scott, J.E. (1988). Proteoglycan-fibrillar collagen interactions. Biochem J 252(2), 313–323.CrossRefGoogle ScholarPubMed
Squirrell, J.M., Wokosin, D.L., White, J.G. & Bavister, B.D. (1999). Long-term two-photon fluorescence imaging of mammalian embryos without compromising viability. Nat Biotechnol 17(8), 763–767.CrossRefGoogle ScholarPubMed
Thornton, G.M., Johnson, J.C., Maser, R.V., Marchuk, L.L., Shrive, N.G. & Frank, C.B. (2005). Strength of medial structures of the knee joint are decreased by isolated injury to the medial collateral ligament and subsequent joint immobilization. J Orthop Res 23(5), 1191–1198.CrossRefGoogle Scholar
Tuthill, T.A., Rubin, J.M., Fowlkes, J.B., Jamadar, D.A. & Bude, R.O. (1999). Frequency analysis of echo texture in tendon. Ultrasound Med Biol 25(6), 959–968.CrossRefGoogle ScholarPubMed
Venkatesan, N., Ebihara, T., Roughley, P.J. & Ludwig, M.S. (2000). Alterations in large and small proteoglycans in bleomycin-induced pulmonary fibrosis in rats. Am J Resp Crit Care Med 161(6), 2066–2073.CrossRefGoogle ScholarPubMed
White, J.G., Squirrell, J.M. & Eliceiri, K.W. (2001). Applying multiphoton imaging to the study of membrane dynamics in living cells. Traffic 2(11), 775–780.CrossRefGoogle Scholar
Wokosin, D.L., Squirrell, J.M., Eliceiri, K.W. & White, J.G. (2003). Optical workstation with concurrent, independent multiphoton imaging and experimental laser microbeam capabilities. Rev Sci Instrum 74(1), 193–201.CrossRefGoogle ScholarPubMed