HEALING OF THE MCL--INTERDISCIPLINARY STUDIES

Summary

Principal Investigator: Savio Woo
Affiliation: University of Pittsburgh
Country: USA
Abstract: The annual incidence of medial collateral ligament (MCL) injuries in the U.S. is estimated to be greater than 60,000, one-third of which have concomitant anterior cruciate ligament (ACL) injuries. Clinically, the injured MCL can heal without operative intervention; however, animal studies have shown that the quality of the healed tissue does not return to pre-injury levels, even after one year. There are concerns that suboptimal healing, especially of combined MCL+ACL injuries, can lead to knee disability. Although many treatment methods have been recommended, there is no consensus of opinion regarding the therapeutic approach to MCL+ACL ligament injuries. Thus, the objective of this study is to systematically identify methods for improving the healing of the injured MCL with growth factors. Four specific aims are proposed: 1) EGF, PDGF-BB, betaFGF and TGF-beta1 will be applied to goat MCL fibroblasts and then isolated MCL injuries to identify the best growth factor and optimal dose. 2) The effects of the optimal growth factor treatment on MCL healing will then be explored in a combined- MCL+ACL injury with ACL reconstruction. 3) Gene transfer technology, which allows repeated percutaneous delivery of growth factors to the injury site, will be explored. 4) The combined MCL+ACL injury with ACL reconstruction will be used to study the effects of growth factors on MCL healing and remodeling up to 2 years post-injury. Using an interdisciplinary approach, the morphological, biochemical, and biomechanical properties of MCL healing will be evaluated and correlated. Morphological analyses will consist of gross, histological, and ultra examination. Biomechanical evaluation will consist of measurements of joint instability as well as tensile and viscoelastic behaviors. Biochemical evaluation will involve the quantification and classification of proteoglycans and the determination of content, typing and cross-linking of collagen. Based on published and ongoing studies, growth factors will aid MCL healing and remodeling, while gene transfer technology offers an exciting opportunity for repeated percutaneous delivery of growth factors. The knowledge gained from this study will increase our understanding of the mechanisms of MCL healing, which could be applied to other ligaments.
Funding Period: 1993-07-20 - 2002-03-31
more information: NIH RePORT

Top Publications

  1. ncbi Downregulation of human type III collagen gene expression by antisense oligodeoxynucleotide
    Fengyan Jia
    Musculoskeletal Research Center, Department of Bioengineering, University of Pittsburgh, Pittsburgh, Pennsylvania 15219, USA
    Tissue Eng 11:1429-35. 2005
  2. ncbi Positive changes in bone marrow-derived cells in response to culture on an aligned bioscaffold
    Alejandro J Almarza
    Musculoskeletal Research Center, Department of Bioengineering, University of Pittsburgh, Pittsburgh, Pennsylvania, USA
    Tissue Eng Part A 14:1489-95. 2008
  3. ncbi Contribution of biomechanics to management of ligament and tendon injuries
    Savio L Y Woo
    Musculoskeletal Research Center, Department of Bioengineering, University of Pittsburgh, 405 Center for Bioengineering, 300 Technology Drive, Pittsburgh, PA 15219, USA
    Mol Cell Biomech 5:49-68. 2008
  4. ncbi Effects of a bioscaffold on collagen fibrillogenesis in healing medial collateral ligament in rabbits
    Rui Liang
    Musculoskeletal Research Center, Department of Bioengineering, University of Pittsburgh, 300 Technology Drive, Pittsburgh, Pennsylvania 15219, USA
    J Orthop Res 26:1098-104. 2008
  5. ncbi Tensile properties of five commonly used mid-urethral slings relative to the TVT
    Pamela A Moalli
    Magee Womens Research Institute, University of Pittsburgh, 300 Halket Street, Pittsburgh, PA 15213, USA
    Int Urogynecol J Pelvic Floor Dysfunct 19:655-63. 2008
  6. ncbi Use of a bioscaffold to improve healing of a patellar tendon defect after graft harvest for ACL reconstruction: A study in rabbits
    Sinan Karaoglu
    Musculoskeletal Research Center, Department of Bioengineering, University of Pittsburgh, 405 Center for Bioengineering, 300 Technology Drive, Pittsburgh, Pennsylvania 15219, USA
    J Orthop Res 26:255-63. 2008
  7. ncbi Gene expression by fibroblasts seeded on small intestinal submucosa and subjected to cyclic stretching
    Thomas W Gilbert
    McGowan Institute for Regenerative Medicine, University of Pittsburgh, Pittsburgh, Pennsylvania, USA
    Tissue Eng 13:1313-23. 2007
  8. ncbi Fiber kinematics of small intestinal submucosa under biaxial and uniaxial stretch
    Thomas W Gilbert
    Department of Bioengineering, McGowan Institute of Regenerative Medicine, University of Pittsburgh, Pittsburgh, PA 15219, USA
    J Biomech Eng 128:890-8. 2006
  9. ncbi The effects of refreezing on the viscoelastic and tensile properties of ligaments
    Daniel K Moon
    Musculoskeletal Research Center, Department of Bioengineering, University of Pittsburgh, 405 Center for Bioengineering, 300 Technology Drive, Pittsburgh, PA 15219, USA
    J Biomech 39:1153-7. 2006
  10. ncbi Long-term effects of porcine small intestine submucosa on the healing of medial collateral ligament: a functional tissue engineering study
    Rui Liang
    Musculoskeletal Research Center, Department of Bioengineering, University of Pittsburgh, 405 Center for Bioengineering, 300 Technology Drive, Pittsburgh, Pennsylvania 15219, USA
    J Orthop Res 24:811-9. 2006

Scientific Experts

  • Savio Woo
  • Pamela Moalli
  • Rui Liang
  • Steven D Abramowitch
  • Daniel K Moon
  • Alejandro J Almarza
  • Thomas W Gilbert
  • Fengyan Jia
  • Sinan Karaoglu
  • Tan D Nguyen
  • Stephen F Badylak
  • Yoshiyuki Takakura
  • Guoguang Yang
  • Matthew B Fisher
  • Alejandro Almarza
  • Ping-Cheng Liu
  • Yin-Chih Fu
  • Ping Cheng Liu
  • Tan Nguyen
  • Yin Chih Fu
  • Serena M Augustine
  • Ann M Stewart-Akers
  • Ann M Stewart Akers
  • Jennifer Sydeski
  • Mary T Gabriel
  • Jonathan S Grashow
  • Michael S Sacks
  • Michael B Chancellor
  • Christopher Niyibizi
  • Takatoshi Shimomura

Detail Information

Publications14

  1. ncbi Downregulation of human type III collagen gene expression by antisense oligodeoxynucleotide
    Fengyan Jia
    Musculoskeletal Research Center, Department of Bioengineering, University of Pittsburgh, Pittsburgh, Pennsylvania 15219, USA
    Tissue Eng 11:1429-35. 2005
    ..Therefore, this approach offers the potential to explore the effect of the reduction of type III collagen in healing ligaments and tendons as a means to improve their mechanical properties...
  2. ncbi Positive changes in bone marrow-derived cells in response to culture on an aligned bioscaffold
    Alejandro J Almarza
    Musculoskeletal Research Center, Department of Bioengineering, University of Pittsburgh, Pittsburgh, Pennsylvania, USA
    Tissue Eng Part A 14:1489-95. 2008
    ....
  3. ncbi Contribution of biomechanics to management of ligament and tendon injuries
    Savio L Y Woo
    Musculoskeletal Research Center, Department of Bioengineering, University of Pittsburgh, 405 Center for Bioengineering, 300 Technology Drive, Pittsburgh, PA 15219, USA
    Mol Cell Biomech 5:49-68. 2008
    ..Yet, solving new and more complex problems must still follow the stepwise methods of approach as taught by Professor Fung...
  4. ncbi Effects of a bioscaffold on collagen fibrillogenesis in healing medial collateral ligament in rabbits
    Rui Liang
    Musculoskeletal Research Center, Department of Bioengineering, University of Pittsburgh, 300 Technology Drive, Pittsburgh, Pennsylvania 15219, USA
    J Orthop Res 26:1098-104. 2008
    ..05). Such significant reduction in the gene expressions are closely related to the improved morphological characteristics, which are known to be coupled with better mechanical properties, as previously reported in longer term studies...
  5. ncbi Tensile properties of five commonly used mid-urethral slings relative to the TVT
    Pamela A Moalli
    Magee Womens Research Institute, University of Pittsburgh, 300 Halket Street, Pittsburgh, PA 15213, USA
    Int Urogynecol J Pelvic Floor Dysfunct 19:655-63. 2008
    ..With the exception of AMS, the overall effect of newer sling modifications was an increase in tensile stiffness...
  6. ncbi Use of a bioscaffold to improve healing of a patellar tendon defect after graft harvest for ACL reconstruction: A study in rabbits
    Sinan Karaoglu
    Musculoskeletal Research Center, Department of Bioengineering, University of Pittsburgh, 405 Center for Bioengineering, 300 Technology Drive, Pittsburgh, Pennsylvania 15219, USA
    J Orthop Res 26:255-63. 2008
    ..SIS treatment increased the quantity of healing tissue, improved the histological appearance and biomechanical properties of the neo-PT, and prevented adhesion formation between the PT and fat pad...
  7. ncbi Gene expression by fibroblasts seeded on small intestinal submucosa and subjected to cyclic stretching
    Thomas W Gilbert
    McGowan Institute for Regenerative Medicine, University of Pittsburgh, Pittsburgh, Pennsylvania, USA
    Tissue Eng 13:1313-23. 2007
    ....
  8. ncbi Fiber kinematics of small intestinal submucosa under biaxial and uniaxial stretch
    Thomas W Gilbert
    Department of Bioengineering, McGowan Institute of Regenerative Medicine, University of Pittsburgh, Pittsburgh, PA 15219, USA
    J Biomech Eng 128:890-8. 2006
    ..Nonaffine structural models will be necessary to fully predict the fiber kinematics under large uniaxial strains in SIS...
  9. ncbi The effects of refreezing on the viscoelastic and tensile properties of ligaments
    Daniel K Moon
    Musculoskeletal Research Center, Department of Bioengineering, University of Pittsburgh, 405 Center for Bioengineering, 300 Technology Drive, Pittsburgh, PA 15219, USA
    J Biomech 39:1153-7. 2006
    ..68). These results suggest that careful refreezing of the specimens had little or no effect on the biomechanical properties measured...
  10. ncbi Long-term effects of porcine small intestine submucosa on the healing of medial collateral ligament: a functional tissue engineering study
    Rui Liang
    Musculoskeletal Research Center, Department of Bioengineering, University of Pittsburgh, 405 Center for Bioengineering, 300 Technology Drive, Pittsburgh, Pennsylvania 15219, USA
    J Orthop Res 24:811-9. 2006
    ..05). The findings extend the shorter term 12-week results, and support the potential of porcine SIS as a bioscaffold to enhance ligament healing...
  11. ncbi Treatment with bioscaffold enhances the the fibril morphology and the collagen composition of healing medial collateral ligament in rabbits
    Savio L Y Woo
    Musculoskeletal Research Center, Department of Bioengineering University of Pittsburgh, Pittsburgh, Pennsylvania, USA
    Tissue Eng 12:159-66. 2006
    ..05). These improvements in the morphological characteristics and biochemical constituents of healing MCLs following SIS treatment are the likely reasons for improved mechanical properties...
  12. ncbi The development and validation of a charge-coupled device laser reflectance system to measure the complex cross-sectional shape and area of soft tissues
    Daniel K Moon
    Musculoskeletal Research Center, Department of Bioengineering, University of Pittsburgh, Pittsburgh, PA 15213, USA
    J Biomech 39:3071-5. 2006
    ..Thus, the CCD laser reflectance system is an improved method for measuring the cross-sectional shape and area of soft tissues since it can detect and account for concavities without physically contacting the specimen...
  13. ncbi Biomechanics of knee ligaments: injury, healing, and repair
    Savio L Y Woo
    Department of Bioengineering, Musculoskeletal Research Center, University of Pittsburgh, Pittsburgh, PA 15219, USA
    J Biomech 39:1-20. 2006
    ..The research summarized here is multidisciplinary and cutting edge that will ultimately help improve the treatment of ligament injuries. The material presented should serve as an inspiration to future investigators...
  14. ncbi Changes in gene expression of matrix constituents with respect to passage of ligament and tendon fibroblasts
    Alejandro J Almarza
    Musculoskeletal Research Center, 405 Center for Bioengineering, Department of Bioengineering, University of Pittsburgh, 300 Technology Drive, Pittsburgh, PA 15219, USA
    Ann Biomed Eng 36:1927-33. 2008
    ....