A. Anatomy and function
1. Function—To transfer force from muscle to bone to produce joint motion.
2. Composition and structure
a. Tendon is made up of collagen fibers embedded in water and a proteoglycan matrix. The tissue is relatively acellular.
b. The fibroblast is the predominant cell type in tendon. In longitudinal histologic sections, fibroblasts appear spindle shaped, with the preferred orientation in the direction of muscle loading. In cross section, fibroblasts are star shaped, with long cytoplasmic processes.
c. Tendon has a clearly defined hierarchical structure (
Figure 1). Collections of collagen molecules are arranged in quarter-stagger arrays, forming ordered units of microfibrils, which combine to form subfibrils, which further combine to form fibrils. Fibril units then form highly ordered parallel bundles oriented in the direction of muscle force. Fibrils accumulate to form fascicle units, which in turn combine to form the tendon.
d. Type I collagen is the major constituent of tendon (86% of the dry weight). The primary structure of collagen consists of glycine (33%), proline (15%), and hydroxyproline (15%). The collagen molecule is fibrillar in structure, with a length of 300 nm and a diameter of 1.5 nm.
e. Proteoglycans make up from 1% to 5% of the dry weight of a tendon. Proteoglycans are highly hydrophilic and therefore bind tightly to water.
f. Decorin is the predominant proteoglycan in tendon.
i. The role of decorin during development and healing is to regulate collagen fiber diameter. The presence of decorin inhibits lateral fusion of collagen fibers.
ii. The role of decorin during normal function is to transfer loads between collagen fibers. Decorin molecules form cross-links between collagen fibers and can therefore increase the stiffness of the fibrils.
g. Aggrecan (a proteoglycan abundant in articular cartilage) is found in areas of tendon that are under compression (eg, regions of hand flexor tendons that wrap around bone).
h. The vascularity of tendon varies. Sheathed tendons (eg, flexor tendons of the hand) have regions that are relatively avascular. These regions get nutrition through diffusion from the synovium. Tendons not enclosed by a sheath receive their blood supply from vessels entering from the tendon surface or from the tendon-to-bone insertion.
a. Tendons have high tensile properties and buckle under compression (ie, they behave like ropes). A typical load-elongation curve for tendon includes a toe region, a linear region, and a failure region (
b. Tendon biomechanics can be characterized by either structural properties (load-elongation behavior) or material properties (stress-strain behavior, where stress is calculated by dividing
[Figure 1. Tendon tissue has a highly ordered hierarchical structure.]
[Figure 2. The tensile behavior of tendon and ligament tissue includes a nonlinear toe region at low loads, a linear region at intermediate loads, and a failure region at high loads.]
load by cross-sectional area and strain is calculated by dividing change in elongation by initial length).
i. Structural properties describe the overall load-bearing capacity of the tissue and include the contribution of the muscle and bone attachments as well as the geometry of the tissue (cross-sectional area and length). Structural properties include stiffness (the slope of the linear portion of the curve in Figure 2) and failure load.
ii. Material properties (also referred to as mechanical properties) describe the quality of the tissue by normalizing for tissue geometry. Material properties include the modulus of elasticity (the slope of the linear portion of the stress-strain curve) and failure stress.
c. Tendons exhibit viscoelastic behavior; the mechanical properties of the tissue are dependent on loading history and time. Time dependence is best illustrated by the phenomena of creep and stress relaxation.
i. Stress relaxation—The decrease in load/stress for a constant elongation/strain.
ii. Creep—The increase in elongation/strain for a constant applied load/stress.
d. Several factors influence the biomechanical properties of tendons.
i. Anatomic location—Tendons from different locations have different structural properties; eg, digital flexor tendons have twice the ultimate strength of digital extensor tendons.
ii. Exercise and immobilization—Exercise has a positive effect and immobilization has a detrimental effect on the biomechanical properties of tendons (
[Figure 3. Immobilization leads to a dramatic drop in mechanical properties, and exercise has a positive effect on mechanical properties.]
iii. Age—Material and structural properties of tendons increase from birth through maturity. The properties then decrease from maturity through old age.
iv. Laser/heat treatment causes tendons to shrink. Long-term effects are unclear, but early evidence suggests that laser/heat treatment has a detrimental effect on the biomechanical properties of the tissue.
e. Factors to consider when mechanically testing tendons:
i. The mechanical properties of tendons vary with hydration, temperature, and pH, so tendons should be tested under physiologically relevant hydration, temperature, and pH conditions.
ii. The high strength of tendons leads to difficulty in gripping the tissue during mechanical testing. Specialized grips (eg, freeze clamps) are often necessary to prevent the tendon from slipping out of the grip.
iii. Knowledge of tissue cross-sectional area is necessary for the calculation of stress (recall that stress = load/cross-sectional area). Care must be taken when measuring the cross-sectional area of tendon because the tissue will deform if contact methods are used (eg, calipers).
iv. Because tendons are viscoelastic (their properties are time dependent), the rate at which the tendon is pulled can influence the mechanical properties. Higher strain rates result in a higher elastic modulus.
v. Specimens should be stored frozen and properly hydrated. Improper storage may affect tendon mechanical properties.
vi. The orientation of a tendon during testing will influence the mechanical properties measured; eg, the structural properties of the supraspinatus tendon depends on the angle of the humeral head relative to the glenoid.
B. Injury, repair, and healing
1. Tendon injury occurs because of direct trauma (eg, laceration of a flexor tendon) or indirect tensile overload (eg, Achilles tendon rupture).
2. Three phases of healing:
a. Hemostasis/inflammation—After injury, the wound site is infiltrated by inflammatory cells. Platelets aggregate at the wound and create a fibrin clot to stabilize the torn tendon edges. The length of this phase is on the order of days.
b. Matrix and cell proliferation—Fibroblasts infiltrate the wound site and proliferate. They produce extracellular matrix, including large amounts of type III collagen. The injury response in adult tendon is scar mediated (ie, large amounts of disorganized collagen are deposited at the repair site). The length of this phase is on the order of weeks.
c. Remodeling/maturation—Matrix metalloproteinases degrade the collagen matrix, replacing type III collagen with type I collagen. Collagen fibers are reorganized so that they are aligned in the direction of muscle loading. The length of this phase is on the order of months or years.
3. Long-term effects—The structural properties of repaired tendons typically reach only two thirds of normal, even years after repair. Material property differences are even more dramatic.
4. Sheathed tendons—Often injured through direct trauma (eg, laceration of a flexor tendon). The two critical considerations for sheathed tendon healing are prevention of adhesion formation and accrual of mechanical strength (
5. Tendons not enclosed in sheaths fail because of trauma (eg, an acute sports injury) or preexisting pathology (eg, a rotator cuff tear after years of chronic tendon degeneration). Injury often occurs at the attachments of the tendon (ie, at the musculotendinous junction or at the tendon-to-bone insertion).
[Figure 4. Sheathed tendons heal primarily through infiltration of fibroblasts from the outer and inner surfaces of the tendon (black arrows). Adhesions between the outer surface of the tendon and the sheath (white arrows) can be prevented with passive motion rehabilitation.]
6. The role of the mechanical environment in healing is complex.
a. Protective immobilization in the early period after tendon repair is beneficial in many scenarios (eg, after rotator cuff repair).
b. Exercise can be detrimental if started too early in the rehabilitation period, but it is beneficial during the remodeling phase of healing.
c. Early passive motion is beneficial for flexor tendon healing. Early motion suppresses adhesion formation between the tendon and the sheath, preventing the typical range of motion losses seen with immobilized tendons.
A. Anatomy and function
1. The function of ligaments is to restrict joint motion (ie, to stabilize joints).
2. Composition and structure
a. Ligaments are composed of dense connective tissue.
b. Ligaments are similar in composition and structure to tendons, but there are several important differences (
i. Ligaments are shorter and wider.
ii. Ligaments have a lower percentage of collagen and a higher percentage of proteoglycans and water.
[Figure 5. The biochemical composition of a typical ligament.]
iii. Collagen fibers are less organized in ligaments.
c. Ligaments have a highly ordered hierarchical structure, similar to tendons.
d. Type I collagen makes up 70% of the dry weight of ligaments.
e. Like tendons, the main cell type in ligaments is the fibroblast, but ligament fibroblasts appear rounder than tendon fibroblasts.
f. Ligaments have relatively low vascularity and cellularity.
a. The biomechanical properties of ligaments are expressed as either the structural properties of the bone-ligament-bone complex or the material properties of the ligament midsubstance itself.
b. Ligaments exhibit viscoelastic behavior similar to that of tendons.
c. Several factors that influence the mechanical properties of ligaments are the same as those described earlier for tendon (I.A.3.d).
d. Factors that must be considered when mechanically testing ligaments are the same as those listed earlier for tendon (I.A.3.e).
B. Injury, repair, and healing
1. Ligament injuries are generally classified into three grades (I, II, and III). Grade I corresponds to a mild sprain, grade II corresponds to a moderate sprain/partial tear, and grade III corresponds to a complete ligament tear. An additional type of injury is avulsion of the ligament from its bony insertion.
2. Ligament healing occurs through the same phases as tendon healing (hemostasis/inflammation, matrix and cell proliferation, remodeling/maturation).
3. Extra-articular ligaments (eg, the medial collateral ligament (MCL) of the knee) have a greater capacity to heal than do intra-articular ligaments (eg, ACL of the knee).
a. MCL of the knee
i. Grade I and II injuries to the MCL heal without surgical treatment.
ii. The optimal treatment of grade III MCL injuries is controversial. Up to 25% of patients with these injuries continue to have clinical problems whether or not the tear is surgically repaired.
b. Anterior cruciate ligament (ACL) of the knee—Midsubstance ACL injuries typically do not heal. Surgical reconstruction of the ACL often is necessary to restore stability in the injured knee. Several graft materials have been used to reconstruct the ACL, including both autograft and allograft.
i. Autografts, including bone-patellar tendon-bone, semitendinosus, quadriceps, and gracilis—are commonly used. The structural properties of the reconstructed graft reach only 50% of normal properties at the longest follow-up studied. The major disadvantage of autograft is donor site morbidity.
ii. ACL allografts (taken from cadavers) are also used for ACL reconstruction. Disadvantages of these grafts include the potential for disease transmission and the loss of mechanical properties because of graft sterilization.
iii. A process described as "ligamentization" occurs in both auto- and allografts after reconstruction when a tendon is used to replace the function of a ligament. Autograft fibroblasts die soon after reconstruction and are replaced by local fibroblasts. Similarly, allografts are infiltrated by local fibroblasts in the early period after implantation.
III. Enthesis (Tendon/Ligament-Bone Junction)
A. Anatomy and function
1. Tendons and ligaments insert into bone across a complex transitional tissue, the enthesis.
2. Composition and structure
a. Indirect insertions (eg, the femoral insertion of the MCL)—The superficial layer connects with the periosteum and the deep layer anchors to bone via Sharpey fibers.
b. Direct insertions (eg, the supraspinatus insertion of the rotator cuff) have classically been categorized into four zones.
i. First zone: tendon proper; properties similar to those found at the tendon midsubstance. Consists of well-aligned type I collagen fibers with small amounts of the proteoglycan decorin.
ii. Second zone: fibrocartilage; marks the beginning of the transition from tendinous material to bony material. Composed of types II and III collagen, with small amounts of types I, IX, and X collagen, and small amounts of the proteoglycans aggrecan and decorin.
iii. Third zone: mineralized fibrocartilage, indicating a marked transition toward bony tissue. Predominant collagen is type II, with significant amounts of type X collagen and aggrecan.
iv. Zone four: bone, which is made up predominantly of type I collagen with a high mineral content.
c. Although the insertion site is typically categorized into four zones, changes in the tissue are gradual and continuous. This continuous change in tissue composition is presumed to aid in the efficient transfer of load between two very different materials.
a. A fibrocartilaginous transition is necessary to reduce stress concentrations that would otherwise arise at the interface of two very different materials (tendon/ligament and bone).
b. The enthesis typically has lower mechanical properties in tension than does the tendon or ligament midsubstance.
B. Injury, repair, and healing
1. Tendon-to-bone and ligament-to-bone healing is necessary in several scenarios.
a. Rotator cuff injuries, which represent most soft-tissue injuries to the upper extremities, commonly require surgical repair to the humeral head.
b. Typical ACL reconstruction techniques use tendon grafts that must heal in tibial and femoral bone tunnels.
c. Avulsion injuries to the flexor tendons of the hand require tendon-to-bone repair.
2. In most cases of tendon-to-bone healing, clinical outcomes have been disappointing. The most dramatic feature of the failed healing response is the lack of a transition zone between the healing tendon and bone. Regeneration of the natural transitional tissue between tendon and bone is critical for the restoration of joint function and for the prevention of reinjury.
IV. Tissue Engineering
1. Definition—Tissue engineering is the regeneration of injured tissue through the merging of three areas: scaffold microenvironment, responding cells, and signaling biofactors.
2. Tissue engineering holds great promise for improving tendon and ligament repair.
1. Can serve as a delivery system for biofactors, an environment to attract or immobilize cells, and/or a mechanical stabilizer.
2. Scaffold matrices commonly are made of collagen, fibrin, polymer, or silk.
C. Responding cells
1. Tendon/ligament fibroblasts, mesenchymal stem cells
2. May either be seeded onto the scaffold before implantation or may infiltrate the acellular scaffold after it is implanted.
D. Signaling biofactors
1. Growth factors
a. Platelet-derived growth factor-BB (PDGF-BB) promotes cell proliferation and matrix synthesis.
b. Transforming growth factor-beta (TGF-β) promotes matrix synthesis.
c. Basic fibroblast growth factor (bFGF) promotes cell proliferation and matrix synthesis.
2. Mechanical signals
a. Cyclic tensile loads promote matrix synthesis.
b. Compressive loads promote proteoglycan production.
Top Testing Facts
1. Tendons and ligaments are materials with highly ordered hierarchical structure.
2. The composition of tendons and ligaments is primarily type I collagen, aligned in the direction of loading (anisotropic).
3. Structural properties describe the capacity of the tissue to bear load; material properties describe the quality of the tissue.
4. Tendons and ligaments are viscoelastic (their properties are time dependent).
5. Several biologic (eg, age) and environmental (eg, temperature) factors influence the mechanical properties of tendons and ligaments.
6. Tendon/ligament healing progresses through clearly defined phases: hemostasis/inflammation, matrix and cell proliferation, and remodeling/maturation.
7. Nonsheathed tendons and extra-articular ligaments have a greater capacity to heal than do sheathed tendons and intra-articular ligaments.
8. For tendon and ligament healing, increased loading can be either beneficial or detrimental, depending on the anatomic location and type of injury.
9. The physical environment influences tissue maintenance: immobilization is detrimental and exercise is beneficial to the biomechanical properties of these tissues (tendon and ligament).
10. The tendon/ligament enthesis is a specialized tissue that is necessary to minimize stress concentrations at the interface between two very different materials (tendon/ligament and bone).
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