Review
Biomechanics of knee ligaments: injury, healing, and repair

https://doi.org/10.1016/j.jbiomech.2004.10.025Get rights and content

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.

Introduction

Injuries to knee ligaments are very common. It has been estimated that the incidence could be at 2/1000 people per year in the general population (Miyasaka et al., 1991) and a much higher rate for those involved in sports activities (Bruesch and Holzach, 1993). Ninety percent of knee ligament injuries involve the anterior cruciate ligament (ACL) and the medial collateral ligament (MCL) (Miyasaka et al., 1991). In fact, recent studies have documented that ACL injuries in females are reaching epidemic proportions with the frequency of rupture more than 3 times greater than that of their male counterparts (Anderson et al., 2001; Arendt and Dick, 1995; Powell and Barber-Foss, 2000). The results of ligament injuries can be devastating. Frequently, surgery is required, but the outcomes are variable. Further, post-surgical rehabilitation could require an extended absence from work or athletic competition.

Basic science and clinical studies have revealed that a ruptured MCL can heal spontaneously (Frank et al., 1983; Indelicato, 1983; Jokl et al., 1984; Kannus, 1988). However, laboratory studies have shown that its ultrastructure and biochemical composition remain significantly altered (Frank et al., 1983; Niyibizi et al., 2000; Weiss et al., 1991). Furthermore, the mechanical properties of the ligament substance remain substantially inferior to those of normal ligaments even after years of remodeling (Loitz-Ramage et al., 1997; Ohland et al., 1991). On the other hand, midsubstance tears of the ACL and posterior cruciate ligament (PCL) would not heal spontaneously and surgical reconstruction using a replacement graft is often required (Hirshman et al., 1990; Kannus and Jarvinen, 1987). While the majority of ligament reconstructions yield good short-term clinical results, 20–25% of patients experience complications including instability that could progressively damage other knee structures (Aglietti et al., 1997; Bach et al., 1998; Daniel et al., 1994; Jomha et al., 1999; Ritchie and Parker, 1996; Shelbourne et al., 1995; Yagi et al., 2002).

Thus, there has been a tremendous quest for knowledge to better understand ligament injuries, healing and remodeling in hope to develop new and improved treatment strategies. The needs in meeting this goal have stimulated researchers to seek new and innovative methods of investigation. Because of the complex biological process, it has become clear that collaborations from different disciplines rather than an individualistic approach in research must be developed. In this review, the properties of normal ligaments, including their anatomical, biological, biochemical and mechanical properties, as well as the changes that occur following injury will be described. The MCL will be used as a model because of its uniform cross-sectional area, large aspect ratio, and propensity for healing. Subsequently, novel functional tissue engineering methodologies and some of the early findings will be presented. The challenging problems which remain to be solved and the potential of new treatment strategies will be explored. In terms of ligament reconstruction, the biomechanics of surgical reconstruction of the ACL and the utilization of robotics technology to study some of the key surgical parameters that affect the performance of the replacement grafts will be reviewed. It is hoped that these creative research approaches will inspire many to join this course of investigation and ultimately help improve the treatment of ligament injuries.

Section snippets

Anatomy, histological appearance and biochemical constituents of normal ligaments

Ligaments are composed of closely packed collagen fiber bundles oriented in a parallel fashion to provide for stability of joints in the musculoskeletal system. The major cell type is the fibroblast and they are interspersed in the parallel bundles of collagen.

In the human knee, the MCL is approximately 80 mm long and runs from the medial femoral epicondyle distally and anteriorly to the posteromedial margin of the metaphysis of the tibia. The lateral collateral ligament (LCL) originates from

Tensile properties of ligaments

Ligaments are best suited to transfer load from bone to bone along the longitudinal direction of the ligament. Thus, their properties are commonly studied via a uniaxial tensile test of a bone–ligament–bone complex (e.g. femur-MCL-tibia complex). These tests result in a load–elongation curve that is non-linear and concave upward. This enables ligaments to help to maintain smooth movement of joints under normal, physiologic circumstances and to restrain excessive joint displacements under high

Viscoelastic properties of ligaments

The complex interactions of collagen with elastin, proteoglycans, ground substance, and water results in the time- and history-dependent viscoelastic behaviors of ligaments. In response to various tensile loading protocols, ligaments exhibit hysteresis (i.e. internal energy dissipation), creep, and stress relaxation. The following is a comprehensive review of the theories to describe these properties.

MCL healing

Because the injured MCL of the knee can heal spontaneously, it has been used as an excellent experiment model for many studies, especially those from the rabbit (Weiss et al., 1991; Woo et al., 1987, Woo et al., 1987). These studies have helped to understand that the rate, quality and composition of the healing MCL are dependent on the treatment modality. Conservative treatment of an isolated MCL injury produced better results to those with surgical repair either with or without immobilization (

New approaches to improve healing of ligaments—functional tissue engineering

In order to improve the quality of healing tissues and restore the normal function of ligaments, functional tissue engineering based on novel biological and bioengineering techniques has been explored. Examples include the usage of a variety of growth factors, gene transfer and gene therapy, cell therapy, as well as the use of scaffolding materials. Together with mechanical factors, these technologies offer great potential for the utilization of functional tissue engineering in ligament healing.

ACL reconstruction

It is hoped that the new knowledge gained from studying and treating healing ligaments may one day lead to alternative strategies for treating other ligaments that do not heal (e.g. ACL and PCL of the knee). For now, however, injuries to the ACL and PCL are managed by ligament reconstruction using replacement auto- or allografts. While many patients have benefited from these transplantations, a large percentage (20–25%) of patients for ACL reconstruction and a higher percentage (up to 60%) for

Future directions

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 determining the contribution of ligaments to joint kinematics and function. The tensile and viscoelastic properties of ligaments, together with experimental and biologic factors, have all helped to move the field forward. Further, significant knowledge on the healing process and replacement of ligaments after

Acknowledgements

The authors acknowledge the financial support provided by the National Institute of Health Grants AR41820 and AR39683.

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