ARTICLE IN PRESS
Journal of Biomechanics 39 (2006) 1 20
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Review
Biomechanics of knee ligaments: injury, healing, and repair
Savio L.-Y. Woo , Steven D. Abramowitch, Robert Kilger, Rui Liang
Department of Bioengineering, Musculoskeletal Research Center, University of Pittsburgh, Pittsburgh, PA, 15219, USA
Accepted 20 October 2004
Abstract
Knee ligament injuries are common, particularly in sports and sports related activities. Rupture of these ligaments upsets the
balance between knee mobility and stability, resulting in abnormal knee kinematics and damage to other tissues in and around the
joint that lead to morbidity and pain. During the past three decades, significant advances have been made in characterizing the
biomechanical and biochemical properties of knee ligaments as an individual component as well as their contribution to joint
function. Further, significant knowledge on the healing process and replacement of ligaments after rupture have helped to evaluate
the effectiveness of various treatment procedures.
This review paper provides an overview of the current biological and biomechanical knowledge on normal knee ligaments, as well
as ligament healing and reconstruction following injury. Further, it deals with new and exciting functional tissue engineering
approaches (ex. growth factors, gene transfer and gene therapy, cell therapy, mechanical factors, and the use of scaffolding
materials) aimed at improving the healing of ligaments as well as the interface between a replacement graft and bone. In addition, it
explores the anatomical, biological and functional perspectives of current reconstruction procedures. Through the utilization of
robotics technology and computational modeling, there is a better understanding of the kinematics of the knee and the in situ forces
in knee ligaments and replacement grafts.
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.
r 2004 Elsevier Ltd. All rights reserved.
Keywords: Biomechanics; Knee ligaments; Tissue engineering; Healing
Contents
1. Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 2
2. Anatomy, histological appearance and biochemical constituents of normal ligaments. . . . . . . . . . . . . . . . . . . . . . . . . . . . 3
3. Tensile properties of ligaments . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 4
3.1. Ligament anisotropy. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 4
3.2. Significant biological factors on the properties of ligaments . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 5
4. Viscoelastic properties of ligaments . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 5
4.1. The quasi-linear viscoelastic theory . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 6
4.2. Continuum based viscoelastic models . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 6
Corresponding author. Department of Bioengineering, Musculoskeletal Research Center, 405 Center for Bioengineering, 300 Technology Drive,
P.O. Box 71199, Pittsburgh, PA 15219, USA. Tel.: [phone]; Fax: [phone].
E-mail addresses: [e-mail], [e-mail] (S.L.-Y. Woo).
0021-9290/$ - see front matter r 2004 Elsevier Ltd. All rights reserved.
doi:10.1016/j.jbiomech.2004.10.025
ARTICLE IN PRESS
2 S.L.-Y. Woo et al. / Journal of Biomechanics 39 (2006) 1 20
5. Healing of knee ligaments . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 7
5.1. MCL healing . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 7
5.2. Phases of ligament healing . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 7
5.3. New animal model . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 8
6. New approaches to improve healing of ligaments functional tissue engineering . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 8
6.1. Growth factors . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 8
6.2. Gene transfer and gene therapy . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 9
6.3. Cell therapy. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 9
6.4. Biological scaffolds. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 9
6.5. Mechanical factors . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 10
7. ACL reconstruction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 10
7.1. Graft function . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 10
7.2. Graft incorporation and remodeling. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 13
8. Future directions . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 13
Acknowledgements . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 15
References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 15
1. Introduction majority of ligament reconstructions yield good short-
term clinical results, 20 25% of patients experience
Injuries to knee ligaments are very common. It has complications including instability that could progres-
been estimated that the incidence could be at 2/1000 sively damage other knee structures (Aglietti et al., 1997;
people per year in the general population (Miyasaka et Bach et al., 1998; Daniel et al., 1994; Jomha et al., 1999;
al., 1991) and a much higher rate for those involved in Ritchie and Parker, 1996; Shelbourne et al., 1995; Yagi
sports activities (Bruesch and Holzach, 1993). Ninety et al., 2002).
percent of knee ligament injuries involve the anterior Thus, there has been a tremendous quest for knowl-
cruciate ligament (ACL) and the medial collateral edge to better understand ligament injuries, healing and
ligament (MCL) (Miyasaka et al., 1991). In fact, recent remodeling in hope to develop new and improved
studies have documented that ACL injuries in females treatment strategies. The needs in meeting this goal
are reaching epidemic proportions with the frequency of have stimulated researchers to seek new and innovative
rupture more than 3 times greater than that of their male methods of investigation. Because of the complex
counterparts (Anderson et al., 2001; Arendt and Dick, biological process, it has become clear that collabora-
1995; Powell and Barber-Foss, 2000). The results of tions from different disciplines rather than an indivi-
ligament injuries can be devastating. Frequently, surgery dualistic approach in research must be developed. In this
is required, but the outcomes are variable. Further, review, the properties of normal ligaments, including
post-surgical rehabilitation could require an extended their anatomical, biological, biochemical and mechan-
absence from work or athletic competition. ical properties, as well as the changes that occur
Basic science and clinical studies have revealed that a following injury will be described. The MCL will be
ruptured MCL can heal spontaneously (Frank et al., used as a model because of its uniform cross-sectional
1983; Indelicato, 1983; Jokl et al., 1984; Kannus, 1988). area, large aspect ratio, and propensity for healing.
However, laboratory studies have shown that its Subsequently, novel functional tissue engineering meth-
ultrastructure and biochemical composition remain odologies and some of the early findings will be
significantly altered (Frank et al., 1983; Niyibizi et al., presented. The challenging problems which remain to
2000; Weiss et al., 1991). Furthermore, the mechanical be solved and the potential of new treatment strategies
properties of the ligament substance remain substan- will be explored. In terms of ligament reconstruction, the
tially inferior to those of normal ligaments even after biomechanics of surgical reconstruction of the ACL and
years of remodeling (Loitz-Ramage et al., 1997; Ohland the utilization of robotics technology to study some of
et al., 1991). On the other hand, midsubstance tears of the key surgical parameters that affect the performance
the ACL and posterior cruciate ligament (PCL) would of the replacement grafts will be reviewed. It is hoped
not heal spontaneously and surgical reconstruction that these creative research approaches will inspire many
using a replacement graft is often required (Hirshman to join this course of investigation and ultimately help
et al., 1990; Kannus and Jarvinen, 1987). While the improve the treatment of ligament injuries.