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Paul Banaszkiewicz Paul Banaszkiewicz Section Editor
Francois Tudor Francois Tudor Segment Author
  • Degenerative and/or traumatic tendon injuries are a common cause of orthopaedic referral.
  • They present a clinical challenge to orthopaedic surgeons mainly because these injuries often respond poorly to treatment and require prolonged rehabilitation.
  • Knowledge of injury mechanisms and the tendon healing process are important to aid treatment of these problems.
  • Tendon injury may involve both intrinsic and extrinsic factors. Generally acute ruptures in the absence of preceding problems are due to extrinsic factors such as size and rate of load application.
  • Intrinsic factors such as degenerate changes will predispose to rupture without exceeding the ultimate tensile strength of the tendon. Injury mechanisms can be divided into:
  • Direct trauma/laceration
  • Acute application of tensile loads exceeding the strength of the tendon
  • Degenerative conditions

Direct trauma or laceration

  • e.g. Sharp laceration of a finger flexor tendon.

Acute application of tensile loads exceeding the strength of the tendon

  • Tendon vascularity is compromised at junctional zones and sites of focused torsion, friction, or compression, leading to greater risk of injury. Generally, tendon blood flow also decreases with increasing age and mechanical loading. These junctional locations commonly have distinct injury patterns:
  • Avulsion of the tendon from its bony insertion (the osteotendinous junction has four specialised zones to allow the transition between the flexible tendon and relatively stiffer bone while minimising the rupture risk).
  • Midsubstance rupture (often seen in degenerate tendon).
  • Disruption at the musculotendinous junction (this is the weakest point of the muscle/tendon unit due to the large forces applied to the structure by the adjacent contracting muscle, in spite of tendon collagen fibrils inserting deep into the myocyte processes).

Degenerative conditions

  • Repetitive loading of a tendon at loads below its ultimate tensile strength in general should not lead to rupture. However, a tendon with accumulated damage and inability to repair this damage will be predisposed to rupture. In fact, intrinsic factors such as malalignment and biomechanical derangement of the underlying tendon have been shown to be involved in the majority of Achilles tendon ruptures in athletes.1,2
  • Repetitive overload of a tendon or accumulated micro-trauma leads to intrinsic degeneration, and the relative ischaemia and poor vascularity prevent complete healing. This degeneration predisposes to the risk of rupture.
  • Acute injury
  • Due to a single traumatic event
  • No preceding symptoms
  • Chronic injury(tendinitis-inflammation or tendinosis-degeneration)
  • Insidious onset of symptoms
  • Tendon pain, swelling and crepitus
  • Histological analysis of these injuries has shown them to be predominantly degenerative tendonopathy present that intrinsically weakens the structure and allows rupture to occur.3
  • When a ligament/tendon is subjected to loading of more than the physiological range, microfailure occurs as individual fibres are disrupted, even before the yield point is reached. This causes elongation of the structure despite its remaining macroscopically in continuity.
  • When the yield point is reached, gross failure occurs.

Three grades of ligament or tendon injury occur

  • Grade 1: negligible clinical symptoms, no joint instability clinically, microfailure may have occurred but ligament remains grossly intact. Pain with stress testing of ligament but no laxity.
  • Grade 2: severe pain, the joint is clinically stable with a partial ligament rupture. Partial loss of ligament continuity with obvious increase in laxity.
  • Grade 3: severe pain during the course of the injury, followed by less pain after the injury. The joint is grossly unstable. Most, if not all, collagen fibres are ruptured.

There are a number of factors that affect tendon and ligament structural propertiesand may protect from or predispose to injury.

Age

  • The number and quality of collagen crosslinks increases, leading to an increase in the tensile strength and increased cross-sectional area of collagen fibrils. These changes occur up to the age of 20 years. As age increases, there is a concomitant drop in the collagen content and number of crosslinks in tendons and ligaments. Aging results in a continuous decline in the mechanical properties (strength, stiffness and ability to withstand/recover from deformation).

Mobilisation and training

  • As in most musculoskeletal structures, tendons and ligaments remodel in response to mechanical stresses applied to them. They become stronger and stiffer when subjected to stress. Physical training has been shown to increase the tensile strength of tendons and the ligament–bone interface (in dogs). Conversely, tendons and ligaments become weaker and less stiff when immobilised or not subjected to regular stresses. Studies have shown that it takes up to 12 months to regain the strength and stiffness lost during immobilisation.

Non-steroidal anti-inflammatory drugs (NSAIDs)

  • Research has demonstrated increased total collagen content and tensile strength in animals treated with indomethacin possibly due to increased crosslinkage of collagen. This suggests that short-term use of NSAIDs would not adversely affect tendon healing and may in fact be beneficial to the overall mechanical properties of the structure.
  • Steroids: previously thought to inhibit healing in acute tendon/ligament injuries, animal studies with local steroid at the site of acute injury showed no difference when compared to those without steroid. Local steroids did, however, weaken the strength of the ligament–bone junction.

Pregnancy and hormonal changes

  • There is a marked hormonally driven increase in laxity of tendons and ligaments, particularly in the pelvic region, at the end of pregnancy and during the postpartum period. This eventually returns to normal. Oestrogen fluctuations have also been shown to alter collagen production by up to 50% and may alter the composition of ligaments or tendons, making them susceptible to injury.
  • The severity of a tendon injury is affected by a number of factors associated with the musculotendinous unit as a whole. These include:
  • The amount of force produced by contraction of the muscle to which the tendon is attached.
  • The cross-sectional area of the tendon in relation to that of the attached muscle (a thicker tendon is better able to withstand greater loads).
  • Eccentric contraction of a muscle gives the greatest risk of tendon injury (e.g. forced dorsiflexion of the ankle leads to eccentric contraction of the gastrocnemius, resulting in high tensile forces through the Achilles tendon, potentially causing rupture).
  • Collagen fibres in tendons are nearly parallel, equipping them to withstand high unidirectional loads and thus have a greater yield strength than muscle tissue. This results in muscle injuries being more common than tendon injuries.
  • Tendon and ligament healing is a complex process and while typical histological stages have been defined, the exact molecular signaling and cellular control of the process is poorly understood.
  • The response to injury of different tendons and ligaments differs significantly. Factors that may affect this include:
  • Differences in intrinsic fibroblast response to injury.
  • Apposition of remnants (large gapping or surgical repair).
  • The mechanical environment of the joint or limb involved.
  • Degree of immobilisation of healing tissues.
  • Local environment: infection, tissue loss, vascular injury, presence of synovial fluid (which may have an inhibitory effect on healing).
  • Degree of local and systemic inflammatory response.
  • Healing occurs in three distinct but overlapping periods, similar to bone healing – the acute inflammatory phase, the proliferative/regenerative phase and the remodeling phase.

Inflammatory phase

  • Starts at the time of injury and lasts up to 48 hours. Acute haemorrhage leads to formation of haematoma within the damaged region and an acute inflammatory response. Release of pro-inflammatory cytokines (including platelet-derived growth factor (PDGF), transforming growth factor (TGF)-band fibroblast growth factor).
  • These signaling factors lead to the localisation and recruitment of macrophages, monocytes and neutrophils at the site of injury.
  • The monocytes and macrophages remove debris and damaged cells via phagocytosis.
  • Secreted angiogenic factors initiate the formation of a vascular network, which is responsible for the survival of the newly forming fibrous tissue at the injury site.
  • There is considerable upregulation and release of chemotactic and vasoactive factors resulting in initiation of angiogenesis, tenocyte proliferation recruitment of inflammatory cells. This leads to increased production of signaling markers such as aggreccanases, cyclo-oxygenase (COX)-2 and matrix metalloproteinase P (MMP)-1, MMP-3 and MMP-13 that are vital for extracellular matrix (ECM) network remodeling. Tenocytes will migrate to the area during this phase, initiating type III collagen synthesis.

Proliferative/repair phase

  • Locally released growth factors lead to fibroblast proliferation and formation of an initially disorganised scar tissue with predominantly type III collagen, blood vessels and matrix.
  • Over several weeks, this scar tissue becomes more organised and collagen fibres become aligned with the long axis of the structure. These newly formed collagen fibrils are weaker and smaller than normal. Increasing numbers of proteoglycans and glycosaminoglycans are released into the matrix, also resulting in increased water content.
  • Over several weeks large volumes of type III collagen are deposited as new matrix is formed.

Remodelling phase

  • After a few weeks, the proliferative phase merges into the remodelling phase often lasting for months or even years after the initial injury. During this phase, cellularity and both collagen and glycosaminoglycan synthesis decrease. The repair tissue changes from cellular to fibrous.
  • This phase encompasses two phases:
  • Consolidation
  • Maturation
  • The first substage, consolidation, is characterised by a decrease in cellularity and matrix production, as the tissue becomes more fibrous through the replacement of the weaker type III collagen by type I collagen.
  • Tenocytes and collagen fibres become organised along the longitudinal axis of the tendon, aligned with the direction of any applied stresses and crosslinking of fibrils further strengthens the healing structure.
  • This restores tendon stiffness and tensile strength. After approximately 10 weeks, the maturation stage starts, which includes an increase in collagen fibril crosslinking and the formation of more mature tendonous tissue.
  • During this phase, the fibrous tissue is digested and replaced by more normal scar-like tendon tissue.
  • Two cellular mechanisms of tendon healing, known as extrinsic and intrinsic healing, have been suggested.
  • Healing may occur intrinsically, with the proliferation of epi and endotenon tenocytes, and extrinsically, with the invasion of cells from the surrounding sheath and synovium.
  • First fibroblasts and in?ammatory cells from the tendon periphery, blood vessels and circulation are attracted to the injured site contributing to cell in?ltration and the formation of adhesions. Thereafter, intrinsic cells from the endotenon are activated as they migrate and proliferate at the injury site, reorganising the ECM and giving support to the internal vascular networking.
  • Intrinsic healing results in better biomechanics and a normal gliding mechanism remains within the tendon sheath.
  • Extrinsic healing may result in scar tissue and adhesions, leading to poor tendon gliding within the sheath.
  • Despite this healing mechanism, the mechanical and biochemical properties of healed tendons and ligaments never match those of intact structures.
  • Surgical repair of tendon injuries is standard treatment in some cases (such as the finger flexor tendons) and controversial in others (Achilles tendon rupture). This is due to a number of factors, including potential loss of function and the likelihood and quality of healing.
  • When surgical repair is undertaken, a number of techniques have been described. Repair strength is the most important factor to consider, as the tendon must be able to withstand the forces seen with early mobilisation without gapping at the repair site. Multiple core strands increase repair strength and permit more rigorous rehabilitation without the risk of rupture, which may minimise adhesion formation. However, the increased bulk increases gliding resistance. The addition of a peripheral circumferential suture is now common to ensure tendon ends meet laterally and to provide extra strength. They will also, however, produce resistance to gliding.
  • In addition to considering repair technique, surgeons must be mindful of careful, atraumatic handling of the tendon and accurate, tension-free repair with respect of the vascularity, all in order to increase the success of repair and reduce the risk of adhesions.
  • It is now widely accepted that early active mobilisation of repaired tendons leads to improved strength and formation of fewer adhesions in comparison to immobilised repairs.
  • There are a number of well described protocols currently used in finger flexor tendon repairs with excellent results and functional outcomes.

Factors that adversely affect tendon healing include:

  • Inflammation – although a vital element of the initial healing process, continued inflammatory response leads to healing via scar tissue formation rather than tissue regeneration.
  • Matrix metalloproteinases – upregulated by inflammatory mediators and involved in tendon degeneration, the inhibition of MMP production may lead to better tendon healing.
  • Smoking – has been shown to inhibit tendon healing, possibly due to poor vascularity, chronic inflammatory changes and decreased cell proliferation.
  • Vitamin D deficiency – may be involved in impaired tendon healing.
  • Associated muscle atrophy and fatty degeneration – negatively impacts on tendon healing (as seen in rotator cuff tears).
  • Diabetes – has an adverse impact on normal tendon mechanical properties and may impair healing.
  • Mechanical load – overload or load deprivation can both have detrimental effects on tendon healing. Hence the modern use of early mobilisation protocols, but more information is required.
  • Experimental approaches for enhancing tendon repair consist mainly of applying growth factors, singly or in combination, stem cells in native or genetically modi?ed form, and biomaterials, alone or cell loaded, at the site of tendon damage.

Growth factors

  • Tendon injury stimulates the production of a variety of growth factors at multiple stages in the healing process leading to increased cellularity and tissue volume. Increased expression of growth factors is particularly prominent in the early phases of healing. The following growth factors are important in tendon healing: basic fibroblast growth factor (bFGF), bone morphogenic protein (BMP)-12, BMP-13, BMP-14, connective tissue growth factor (CTGF), insulin-like growth factor (IGF)-1, PDGF, TGF-b, and vascular endothelial growth factor (VEGF). Growth factors can be applied by local injection, percutaneously or operatively, or by implanting scaffolds or even suture material containing growth factors.

Mesenchymal stem cells

  • Mesenchymal stem cells can be applied directly to the site of injury or can be delivered on a suitable carrier matrix, which functions as a scaffold while tissue repair takes place.
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Further Reading

  • 1. An excellent review of the subject can be found in Sharma P, Maffulli N. Tendon injury and tendonopathy: Healing and repair. J Bone Joint Surg 2005; 87(1): 187–202.

References

  • 1. Möller A, Åström M, Westlin NE. Increasing incidence of Achilles tendon rupture. Acta Orthopaed Scand 1996; 67(5): 479–481.
  • 2. Kvist M. Achilles tendon injuries in athletes. Sports Med 1994; 18(3): 173–201.
  • 3. Arnero O, Lindholm A, Orell S. Histologic changes in subcutaneous rupture of the Achilles tendon: a study of 74 cases. Acta Chirurg Scand 1959; 116(5–6): 484.