Ligament structure, physiology and function.
ABSTRACT Ligaments are specialized connective tissues with very interesting biomechanical properties. They have the ability to adapt to the complex functions that each are required to perform. While ligaments were once thought to be inert, they are in fact responsive to many local and systemic factors that influence their function within the organism. Injury to a ligament results in a drastic change in its structure and physiology and creates a situation where ligament function is restored by the formation of scar tissue that is biologically and biomechanically inferior to the tissue it replaces. This article will briefly review the basic structure, physiology and function of normal versus healing knee ligaments, referring specifically to what is known about two of the most extensively studied and clinically relevant knee ligaments, the anterior cruciate (ACL) and medial collateral (MCL) ligaments of the knee. Those readers wishing for more comprehensive sources of information on ligament biology and biomechanics are referred to many excellent reviews on these topics.
- 01/1988: pages 45-101; American Academy of Orthopaedic Surgeons.
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ABSTRACT: The thin layer of connective tissue covering ligaments--the epiligament--has not been well described. The aim of the present study was to define, describe, and quantify the structure of the epiligament of the rabbit medial collateral ligament (MCL) using polarized light, scanning-electron, transmission-electron microscopy, and computerized histomorphometry. Epiligament was composed of woven bundles of collagen fibers, 3 morphologically-distinct cell types (spinous-shaped cells, cuboidal-shaped cells, and fat cells), and a neurovascular network that periodically arborized into the MCL. The areal fraction of vessels was significantly greater in the epiligament than in the MCL. The epiligament was significantly thicker on the superficial surface of the MCL than the deep surface, and the thickness of epiligament changed significantly during skeletal growth. Based on these structural features we speculate that the epiligament serves several important functions including: (1) protecting the MCL against abrasion, (2) supporting the neurovasculature, (3) controlling water and metabolite flux into the epiligament and possibly the MCL, and (4) being a source of extracellular matrix, cells, and vasculature during ligament growth and during ligament healing.Connective Tissue Research 02/1991; 27(1):33-50. · 1.79 Impact Factor
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ABSTRACT: Recently, an expanding body of knowledge has documented the nature and functions of receptors in joint tissues and their potential importance in preserving the smooth normal functioning of the motor-skeletal system and in amplifying the inflammatory response to joint injuries and diseases. This review summarizes the current knowledge of the anatomical and physiological substrates of these mechanisms. The distribution, morphologic and functional characteristics of joint receptors have been well described. In the past decade there has been a new appreciation of the major role played by sensory neurons in promoting regional inflammatory responses, and many of the specific neuronal mechanisms and molecules that mediate these reflexes have been identified. This knowledge promises to significantly improve the selectivity and effectiveness of pharmacologic approaches to pain, trauma and regional inflammatory disorders. Other investigations have revealed important contributions of joint receptors to motor function. These refer not to proprioception or the sense of limb position in space, but rather to a more sophisticated tailoring of muscle activity to increase joint stability and to protect joint structures from damaging loads. Whether a loss of these reflexes may play a role in the pathogenesis of osteoarthritis remains controversial. However, there is a growing consensus that a loss of these reflexes may contribute to the morbidity associated with disruption of the anterior cruciate ligament. Synovial joints are sites of major interactions between the musculoskeletal and the nervous systems. Understanding the mechanisms that activate and control these interactions will certainly offer the opportunity to develop new, more effective treatments for patients with joint disorders.Canadian journal of surgery. Journal canadien de chirurgie 05/1999; 42(2):91-100. · 1.63 Impact Factor
Normal ligament structure and physiology
Skeletal ligaments are defined as dense bands of collage-
nous tissue (fibres) that span a joint and then become
anchored to the bone at either end. They vary in size, shape,
orientation and location. Their unique and complex bony
attachments are called insertions and they often involve unusu-
al shapes on the bone that are likely critical to how the fibres
within the ligament are recruited as the joint moves. Ligaments
often have a more vascular overlying layer termed the "epiliga-
ment" covering their surface6and this layer is often indistin-
guishable from the actual ligament and merges into the perios-
teum of the bone around the attachment sites of the ligament.
Removal of the epiligament exposes the fibrous architecture of
the ligament which is further organized hierarchically into
groups of parallel fibres known as bundles that are difficult to
separate suggesting that they are interconnected in some fash-
ion. While the ligament appears as a single structure, with joint
movement, some fibres appear to tighten or loosen depending
on the bone positions and the forces that are applied confirm-
ing that these structures are more complex than originally
thought. The epiligament is more vascular7, receiving its blood
supply from a branch of the superior medial geniculate artery,
than the ligament and more cellular with more sensory and
proprioceptive nerves. These nerves travel in close proximity to
the blood vessels with more nerves nearer to the bony ligament
insertions. Recent reports8,9have suggested that disruptions in
joint innervation combined with injury and ageing may play a
role in the pathogenesis of osteoarthritis although its patho-
genesis is likely multifactorial thus requiring further investiga-
tion to make firm conclusions. At the microscopic level, liga-
ments are much more complex, being composed of cells called
fibroblasts which are surrounded by matrix. The cells are
responsible for matrix synthesis and they are relatively few in
number and represent a small percentage of the total ligament
volume. Although these cells may appear physically and func-
tionally isolated, recent studies have indicated that normal lig-
ament cells may communicate by means of prominent cyto-
plasmic extensions that extend for long distances and connect
to cytoplasmic extensions from adjacent cells, thus forming an
elaborate 3-dimensional architecture10,11. Gap junctions have
also been detected in association with these cell connections
raising the possibility of cell-to-cell communication and the
potential to coordinate cellular and metabolic responses
throughout the tissue. Ligament microstructure can be visual-
ized using polarized light that reveals collagen bundles aligned
along the long axis of the ligament and displaying an underly-
ing "waviness" or crimp along the length. Crimp is thought to
J Musculoskel Neuron Interact 2004; 4(2):199-201
Ligament structure, physiology and function
McCaig Centre for Joint Injury and Arthritis Research, University of Calgary, Calgary, Alberta, Canada
Ligaments are specialized connective tissues with very interesting biomechanical properties. They have the ability to adapt
to the complex functions that each are required to perform. While ligaments were once thought to be inert, they are in fact
responsive to many local and systemic factors that influence their function within the organism. Injury to a ligament results in
a drastic change in its structure and physiology and creates a situation where ligament function is restored by the formation of
scar tissue that is biologically and biomechanically inferior to the tissue it replaces. This article will briefly review the basic
structure, physiology and function of normal versus healing knee ligaments, referring specifically to what is known about two
of the most extensively studied and clinically relevant knee ligaments, the anterior cruciate (ACL) and medial collateral
(MCL) ligaments of the knee. Those readers wishing for more comprehensive sources of information on ligament biology and
biomechanics are referred to many excellent reviews on these topics1-5.
Keywords: Ligament, Structure, Function, Healing, Biomechanics
The author has no conflict of interest.
Corresponding ·uthor: Cyril B. Frank, MD, FRCSC, McCaig Centre for Joint
Injury & Arthritis Research, Department of Surgery, Faculty of Medicine, Uni-
versity of Calgary, 3330 Hospital Drive NW, Calgary, Alberta, Canada, T2N 4N1
Accepted 28 May 2004
C.B. Frank: Ligament structure, physiology and function
play a biomechanical role, possibly relating to the ligaments
loading state with increased loading likely resulting in some
areas of the ligament uncrimping, allowing the ligament to
elongate without sustaining damage12. Biochemically, liga-
ments are approximately two-thirds water and one-third solid
with the water likely responsible for contributing to cellular
function and viscoelastic behaviour. The solid components of
ligaments are principally collagen (type I collagen accounting
for 85% of the collagen and the rest made up of types III, VI,
V, XI and XIV) which accounts for approximately 75% of the
dry weight with the balance being made up by proteoglycans
(<1%), elastin and finally other proteins and glycoproteins
such as actin, laminin and the integrins. Not all of the dry
weight components have been characterized and this remains
an area of continuing research focus. Ultrastructural studies
have revealed that collagen fibres are actually composed of
smaller fibrils. At the molecular level, collagen is synthesized
as procollagen molecules and these are secreted into the extra-
cellular space through structures in the cell called micro-
tubules. Once outside the cell, a post-transitional modification
takes place and the triple helical collagen molecules line up
and begin to form fibrils and then fibres. This step is promot-
ed by a specialized enzyme called lysyl oxidase, which pro-
motes crosslink formation – a process involving placement of
stable crosslinks within and between the molecules. Crosslink
formation is the critical step that gives collagen fibres such
incredible strength. During growth and development,
crosslinks are relatively immature and soluble but with age
they mature and become insoluble and increase in strength.
This process will become much more relevant during the dis-
cussion on healing ligaments.
Normal ligament function
One of the main functions of ligaments is mechanical as they
passively stabilize joints and help in guiding those joints
through their normal range of motion when a tensile load is
applied. Ligaments exhibit nonlinear anisotropic mechanical
behaviour and under low loading conditions they are relatively
compliant, perhaps due to recruitment of "crimped" collagen
fibres as well as to viscoelastic behaviours and interactions of
collagen and other matrix materials. Continued ligament-load-
ing results in increasing stiffness until a stage is reached where
they exhibit nearly linear stiffness and beyond this, then, liga-
ments continue to absorb energy until tensile failure (disrup-
tion). Another ligament function relates to its viscoelastic
behaviour in helping to provide joint homeostasis. Ligaments
"load relax" which means that loads/stresses decrease within
the ligament if they are pulled to constant deformations.
Ligaments also "creep" which is defined as the deformation (or
elongation) under a constant or cyclically repetitive load.
Creep is particularly important when considering joint injury
or reconstructive surgery as excessive creep could result in lax-
ity of the joint thus predisposing it to further injury. A third
function of ligaments is their role in joint proprioception,
which is referred to as the conscious perception of limb posi-
tion in space. In joints such as the knee, proprioception is pro-
vided principally by joint, muscle and cutaneous receptors.
When ligaments are strained, they invoke neurological feed-
back signals that then activate muscular contraction and this
appears to play a role in joint position sense. Although
progress continues to be made to elucidate the role of propri-
oception in normal ligament function and during injury, more
precise quantification is the subject of ongoing analysis.
Ligament response to injury
Ligaments are most often torn in traumatic joint injuries
that can result in either partial or complete ligament disconti-
nuities. Due to the difficulty in studying partial disruptions,
most of the discussion here will be focused on complete dis-
ruptions. Referring to the rabbit model, the medial collateral
ligament (MCL) heals by a process which includes three phas-
es: hemorrhage with inflammation, matrix and cellular prolif-
eration and finally, remodeling and maturation. The first
phase involves retraction of the disrupted ligament ends, for-
mation of a blood clot, which is subsequently resorbed, and
replaced with a heavy cellular infiltrate. Subsequently, a con-
siderable hypertrophic vascular response takes place in the
gap between the disrupted ends and results in an increase in
both vascularity and blood flow, both of which decrease with
time. The proliferative phase is defined as the production of
"scar tissue" (dense, cellular, collagenous connective tissue
matrix bridging the torn MCL ends) by hypertrophic fibrob-
lastic cells. This scar tissue is initially quite disorganized with
more defects (more blood vessels, fat cells, fibroblastic and
inflammatory cells and loose connective tissue) identified his-
tologically than normal ligament matrix13. After a few weeks
of healing, the collagen becomes quite well aligned with the
long axis of the ligament despite the fact that the types of col-
lagen are abnormal (more type III in relation to type I and an
increase in type V) and the collagen fibrils have smaller diam-
eters in the proliferating tissue. The third phase of ligament
healing is matrix remodeling. Defects in the scar become filled
in but although the matrix becomes more ligament-like with
time, some major differences in composition, architecture and
function persist. Differences which persist include altered pro-
teoglycan14(increased biglycan and decreased decorin protein
and mRNA levels) and collagen types15, failure of collagen
crosslinks to mature16, persistence of small collagen fibril
diameters17, altered cell connections18, increased vascularity19,
abnormal innervation, increased cellularity and the incom-
plete resolution of matrix "flaws". The functional recovery of
MCL scars demonstrates a slow recovery of many properties.
During the remodeling phase, viscoelastic properties recover
to within 10-20% of normal, implying that scars tend to stress-
relax to a greater extent, therefore maintaining a load less effi-
ciently than normal ligament. Ligament scars also have inferi-
or creep properties, creeping twice as much as normal MCLs
during cyclic and static loads that are only a fraction of their
failure loads20. Failure behaviours of healing MCLs do not
recover with injured complexes being weaker (50% of normal
C.B. Frank: Ligament structure, physiology and function
failure loads), less stiff and absorbing less energy before fail-
ure than normal MCLs. Biomechanically, ligament recovery
or healing in the long term may be dependent on a number of
variables including the size of the initial gap, whether contact
exists between the torn ligament ends and to what degree of
joint movement they are subjected. Many different strategies
have been employed to "heal" ligaments back to their original
properties and functions; some such as controlled joint
motion21, biochemical modulation, surgical repair22, grafting23,
gene therapy24and tissue engineering25have assisted in our
understanding of ligament healing, however, complete liga-
ment healing continues to be elusive and will remain the con-
tinuing focus of future investigations.
1. Akeson WH, Woo SL-Y, Amiel D, Frank CB. The biol-
ogy of ligaments. In: Funk FJ, Hunter LY (eds)
Rehabilitation of the Injured Knee. Mosby, St Louis;
Frank C, Woo S, Andriacchi T, Brand R, Oakes B,
Dahners L, DeHaven K, Lewis J, Sabiston P. Normal
ligament: structure, function and composition. In: Woo
SL-Y, Buckwalter JA (eds) Injury and Repair of the
Musculoskeletal Soft Tissues. Am Acad Orthop Surg,
Park Ridge; 1988:45-101.
Woo SL, Young EP. Structure and function of tendons
and ligaments. In: Mow VC, Hayes WC (eds) Basic
Orthopaedic Biomechanics. Raven Press, New York;
Lo IKY, Thornton G, Miniaci N, Frank CB, Rattner JB,
Bray RC. Structure and function of diarthrodial joints.
In: McGinty JB (ed) Operative Arthroscopy 3rdEdition.
Lippincott Williams and Wilkins, Philadelphia;
Frank CB, Shrive NG, Lo IKY, Hart DA. Form and func-
tion of tendon and ligament. In: Buckwalter JA, Einhorn
TA, Simon SR (eds) Orthopaedic Basic Science: Biology
and Biomechanics of the Musculoskeletal System. Am
Acad Orthop Surg, Rosemont; 2004: (in press).
Chowdhury P, Matyas JR, Frank CB. The "epiligament"
of the rabbit medial collateral ligament: a quantitative
morphological study. Connect Tissue Res 1991; 27:33-50.
Bray RC. Blood supply of ligaments: a brief overview.
Orthopaedics 1995; 3:39-48.
Salo P. The role of joint innervation in the pathogene-
sis of arthritis. Can J Surg 1999; 42:91-100.
Johansson H, Sjolander P, Sojka P. A sensory role for
the cruciate ligaments. Clin Orthop Relat Res 1991;
10. Benjamin M, Ralphs JR. The cell and developmental
biology of tendons and ligaments. Int Rev Cytol 2000;
11. Lo IK, Chi S, Ivie T, Frank CB, Rattner JB. The cellu-
lar matrix: a feature of tensile bearing dense soft con-
nective tissues. Histol Histopathol 2002; 17:523-537.
12. Amiel D, Chu CR, Lee J. Effect of loading on metabo-
lism and repair of tendons and ligaments. In: Funk FJ,
Hunter LY (eds) Repetitive Motion Disorders of the
Upper Extremity. Am Acad Orthop Surg, Rosemont;
13. Shrive N, Chimich D, Marchuk L, Wilson J, Brant R,
Frank C. Soft-tissue "flaws" are associated with the
material properties of the healing rabbit medial collat-
eral ligament. J Orthop Res 1995; 13:923-929.
14. Plaas AH, Wong-Palms S, Koob T, Hernandez D,
Marchuk L, Frank CB. Proteoglycan metabolism during
repair of the ruptured medial collateral ligament in
skeletally mature rabbits. Arch Biochem Biophys 2000;
15. Amiel D, Frank CB, Harwood FL, Akeson WH,
Kleiner JB. Collagen alteration in medial collateral lig-
ament healing in a rabbit model. Connect Tissue Res
16. Frank C, McDonald D, Wilson J, Eyre D, Shrive N.
Rabbit medial collateral ligament scar weakness is asso-
ciated with decreased collagen pyridinoline crosslink
density. J Orthop Res 1995; 13:157-165.
17. Frank C, McDonald D, Bray D, Bray R, Rangayyan R,
Chimich D, Shrive N. Collagen fibril diameters in the
healing adult rabbit medial collateral ligament. Connect
Tissue Res 1992; 27:251-263.
18. Lo IK, Ou Y, Rattner JP, Hart DA, Marchuk LL, Frank
CB, Rattner JB. J Anat 2002; 200:283-296.
19. Bray RC, Rangayyan RM, Frank CB. Normal and heal-
ing ligament vascularity: a quantitative histological
assessment in the adult rabbit medial collateral liga-
ment. J Anat 1996; 188:87-95.
20. Thornton GM, Leask GP, Shrive NG, Frank CB. Early
medial collateral ligament scars have inferior creep
behaviour. J Orthop Res 2000; 18:238-246.
21. Buckwalter JA. Activity vs. rest in the treatment of bone,
soft tissue and joint injuries. Iowa Orthop J 1995; 15:29-42.
22. Chimich D, Frank C, Shrive N, Dougall H, Bray R. The
effects of initial end contact on medial collateral liga-
ment healing: a morphological and biomechanical study
in a rabbit model. J Orthop Res 1991; 9:37-47.
23. Boorman RS, Thornton GM, Shrive NG, Frank CB.
Ligament grafts become more susceptible to creep with-
in days after surgery: evidence for early enzymatic
degradation of a ligament graft in a rabbit model. Acta
Orthop Scand 2002; 73:568-574.
24. Nakamura N, Hart DA, Boorman RS, Kaneda Y, Shrive
NG, Marchuk LL, Shino K, Ochi T, Frank CB. Decorin
antisense gene therapy improves functional healing of
early rabbit ligament scar with enhanced collagen fibil-
logenesis in vivo. J Orthop Res 2000; 18:517-523.
25. Huard J, Li Y, Peng H, Fu FH. Gene therapy and tissue
engineering for sports medicine. J Gene Med 2003;