Ch 84-88 + F Ch 19

Makeup of Extracellular Matrix of Tendons

Water - 65% wet weight

Collagen - 30% wet weight

Noncollagenous glycoproteins - 5% wet weight

Collagens and proteoglycans accounts for 70-80% of dry weight

What percentage of the total collagen in a tendon is made up of fibril-forming type I collagen?

About 95%

What percentage of the total collagen in a tendon is made up of type III collagen and other minor collagens?

About 5%

What is endotenon or the interfascicular matrix?

Looser connective tissue that groups collagen fibers in subunits

What are fascicles?

Collagen subunits

Structural hierarchy of the tendon from largest unit to smallest

Tendon unit surrounded by paratenon in extrasynovial locations and epitenon in synovial locations

Third-degree fascicle (1-3 mm diameter)

Second-degree fascicle (400- to 1000-um diameter)

First-degree fascicle (15- to 400-um diameter)

Collagen fiber (1- to 20-um diameter)

Collagen fibril (20- to 150-nm diameter)

Collagen triple helix (1-nm diameter)

Synthesis of Collagen Type I

Two identical a-1 chains and one a-2 chain are the molecular substructure for collagen formation Each chain contains around 1050 amino acids wound around one another in a left-handed triple helix Chains then self-assemble to form procollagen with a right-handed triple helical structure Extracellularly, amino- and carboxy-terminal extensions of procollagen are cleaved by procollagenases Resulting tropocollagen polymerizes to form a type I collagen fibril In fibrils, adjacent tropocollagen molecules are displaced from one another about 1/4 of their length (quarter stagger) Growth of the tendon occurs via a "seed-and-feed" mechanism, whereby collagen fibrils form extracellularly and accrete onto the sides of the template fibrils

What are the two classes of regulatory molecules involved in the regulation of linear and lateral fibril growth?

Small leucine-rich proteoglycans (SLRPs)

Fibril-associated collagens with interrupted triple helices (FACITs)

Small Leucine-Rich Proteoglycans (SLRPs)

Two subclasses

In the tendon, decorin (class 1) and fibromodulin (class 2) are dominant in regulation but can be modulated by biglycan (class 1) and lumican (class 2)

Fibril-Associated Collagens with Interrupted Triple Helices (FACITs)

Closely interact with the fibril-forming collagens and affect surface properties as well as fibril packing

FACITs XII and XIV may play a role during tendon development

Cartilage Oligomeric Matrix Protein (COMP)

Second most abundant protein in young tendon to collagen type I

Believed to be involved in the organization of the collagen fibril framework during formation and growth

Bring together five separate collagen molecules in the "quarter stagger" Once these collagen molecules have formed a fibril, COMP no longer functions in binding and is displaced from the collagen fibril

Levels of COMP in tensional regions of equine digital flexor tendons increase dramatically during growth an peak around 2 years of age

Extracellular Composition in the Mid-Substance (Tensional) Tendon

Collagen type I and the small proteoglycans (decorin, fibromodulin, lumican, and mimecan) predominate

Extracellular Composition in the Fibrocartilagenous Zone of the Tendon (e.g. DDFT at the level of the MCPJ/MTPJ)

Rich in collagen type II and the large proteoglycans (aggrecan and versican)

Reflects ability to cope with compressive load

Tenocytes

Constitute 90-95% of the cellular elements of the tendon

Essential for the formation and maintenance of the extracellular matrix

Exhibit long cytoplasmic processes which link together other tenocytes via gap junctions and thereby allow for communication between cells and appropriate responsiveness to mechanical stimuli

Type I Tenocytes

Thin, spindle-shaped nuclei

Type I cells predominate with aging

Type II Tenocytes

More rounded, thick, cigar-shaped nuclei

Less mature tendon has large numbers of type II cells

Type III Tenocytes

Cartilage-like appearance with round nuclei and visible nucleoli

Type III cells are identified in areas subjected to compressive forces (fibrocartilaginous zone)

What makes up the 5-10% of cellular elements of tendons that are not tenocytes?

Remaining 5-10% of cellular elements of tendons consists of chondrocytes at the bone attachment and insertion sites, synovial cells of the tendon sheaths, and vascular cells, including capillary endothelial cells and smooth muscle cells of arterioles

Endotenon (Interfascicular matrix)

Carries blood vessels and nerves

Contains more rounded cells which are believed to represent a source of multipotent stromal cells within the tendon

Contains higher levels of certain growth factors, such as TGF-B, than the content of the fascicles

Continuous with epitenon

Epitenon

Layer of connective tissue surrounding the outside of the tendon

Paratenon

Outside the epitenon around tendons that are not contained within a tendon sheath

Able to stretch considerably and therefore rarely ruptures when a tendon suffers a strain injury

Believed to play important roles in reducing frictional forces between the tendon and the surrounding soft tissues and as a supplier of new blood vessels and cellular elements for repair

Tendon Sheath

Consists of an outer fibrous wall and an inner synovial membrane

Mesotenons

Composed of two layers of synovium

Frequently carry the blood supply to the tendon

What are the two primary processes for nutrient supply of tendons?

Perfusion

Diffusion

Diffusion for Nutrient Supply of Tendons

Diffusion from compartments other than blood occurs primarily through the synovial fluid where the tendon is enclosed by a sheath

What are the three sources from which blood supply in tendons arises?

Proximal from the musculotendinous junction

Distal from the osseous insertion

In between through intra- and extratendinous vessels

Functional Characteristics of Positional Tendons

Flex, extend, or rotate joints

CDET (low-load positional tendon) and DDFT Lower levels of COMP Predominantly large collagen fibrils

Functional Characteristics of Weight- Bearing Tendons

E.g. flexor tendons, suspensory ligament

Located on the palmar/plantar aspect of the equine distal limb

Receive large weight bearing loads

More elastic

Function as elastic energy stores for energy efficient locomotion System optimized by hyperextended MCP and energy being stored in the SDFT and SL

Two weight bearing structures of the distal limb (SDFT and SL) have very similar matrix compositions and configurations High COMP levels Combination of small and large collagen fibrils

What is crimp?

Fascicle waveform in relaxed tendons

- Best seen under polarized light

- Partly responsible for tendon elasticity

Where does the majority of tendon elongation come from?

Majority of tendon elongation comes from the sliding of fascicles over one another rather than stretching of the fascicles themselves Endotenon believed to be critically important Rotational sliding in SDFT fascicles CDET fascicles slide linearly

Viscoelastic Properties of Tendons

Initially tendon stretches under relatively little load which is associated with the elimination of crimp in the fascicles (toe region)

Then curve is almost linear (operating in elastic fashion) The structural property of stiffness (load divided by deformation) is divided from this area of the curve

As the load increases further, there is a change in the gradient such that the tendon becomes less stiff - yield point (end of the linear region) Thought to arise from covalent crosslink rupture and irreversible slippage of collagen fibrils

If the tendon is stretched past the yield point, irreversible damage occurs and the tendon ruptures For SDFT is ~ 12 KN or 1.2 tons (ultimate tensile strength)

If the cross-sectional area and length of the tendon is known, the stress (force/unit area) can be plotted against the strain (change in length over original length) from which the material properties of ultimate tensile strength (N/mm2) and Young's modulus of elasticity (E[Mpa]) can be calculated

In vitro, equine flexor tendons can extend 10-12% of their length before they rupture (ultimate tensile strength) and values of up to 20% have been reported

Ultimate tensile strain reflects only the final strain before rupture and includes the yield portion of the stress-strain curve, which represents irreversible damage to the tendon tissue

Normal Strains in Digital Flexor Tendons at the Walk

3-8%

Normal Strains in Digital Flexor Tendons at the Trot

7-10%

Normal Strains in Digital Flexor Tendons at the Gallop

12-16%

Hysteresis

Difference between the stress-strain relationship when the tendon is loaded and unloaded

Area between the two curves represents the energy lost during the loading cycle (usually about 5%) Much of this energy is lost as heat Core temperatures can rise to as high as 44 C which is potentially damaging to tendon matrix and tenocytes

Loading Rate of Tendons

Rapid loading rate = stiffer tendon

Repeated loading = less stiff tendon

- Conditioning

What are the two mechanisms by which overstrain injuries of tendons occurs?

Sudden overloading of the structure which overwhelms its resistive strength

Injury preceded by a phase of degeneration which induces neither a clinically evident inflammatory reaction nor any reparative response, but instead progressively weakens the tendon

Response of Tendons to Aging and Exercise

Strength of a tendon is correlated to the number and size of the collagen fibrils and intermolecular covalent crosslinks between fibrils Collagen fibrils increase in size during development and in response to increased physical demands or training The conversion of chemically reducible divalent crosslinks to a network of nonreducible trivalent crosslinks is thought to be responsible for a large proportion of this increase in the mechanical strength of tendons as they mature

SDFT and DDFT are mature by 2 years of age Replacement of immature collagen crosslinks with no further increase in collagen fibril size and the cessation of rapid changes in the collagen fibril crimp morphology

Collagen content varies little with age and exercise

A higher proportion of small fibrils were present in the central region of horses exercised long term Suggested to be due to disassembly of the larger diameter fibrils In longer term exercised and older horses, the noncollagenous component of tendon showed an accelerated loss of glycosaminoglycans (GAGs) and COMP

Additional exercise-accelerated degenerative changes that occur inevitably with aging Regional reduction of the collagen crimp angle and length in the central core of the tendon

Under loading conditions, central fibers are straightened first and are more likely to rupture first

What does cycling loading in tendons lead to?

Cyclical loading leads to cumulative fatigue and microdamage of the tendon matrix, with a failure of the resident cell population to repair this damage

What may be involved in the mechanism for the failure of tenocytes to repair or adapt to exercise-induced microdamage in adult horses?

Reduced cell numbers and gap junctions that would enable a coordinated anabolic response

Reduced growth factor stimulus

Cellular senescence

Mechanisms for Tendon Degeneration

Number of loading cycles important

Amount of time spent at the fastest gaits is likely to contribute the most to degeneration

Primary via physical damage

Secondary because of influences on cell metabolism

Physical energy imparted to the tendon under weight-bearing load can directly damage the matrix by disrupting fibers, crosslinks, or actual matrix proteins and can induce proteolytic enzymes

Cleaved matrix proteins, generated either from direct physical forces or from enzymatic cleavage, were associated with tendon damage and can provoke further matrix degradation

Physically induced microdamage of the extracellular matrix can also result in unloading of the damaged fibrils, which results in reduction in loading of the tenocytes

Increase in temperature in SDFT during galloping could be damaging to matrix proteins or cell metabolism

Strain-Induced Tendon Injury

Degeneration is usually the first phase of a tendinopathy

Clinical injury occurs when the highest stresses encountered by the tendon overwhelm its structural integrity, resulting in irreversible damage

Once the peak load on the tendon overcomes its structural strength there is physical disruption to the tendon matrix

Clinical injury varies from fibrillar slippage, with breakage of crosslinking elements, to fibrillar rupture, and in some cases, complete separation of tendon tissue

Damage induces a repair process characterized by inflammation followed by fibroplasia

Risk Factors for Inducing Tendinopathy

Things that act to increase the peak loads on the SDFT

Speed of the horse

Increased peak impact loading

Weight the horse is carrying

Shoeing

Fatigue

Tendon Tears

Most common sites are DDFT (mainly forelimb) and manica flexoria (mainly in the hindlimb) Higher pressures within the compressed portion of the DDFT as it passes over the palmar aspect of the MCP joint may cause bursting of the lateral (less commonly medial) borders of the tendon Manica tears may develop because it impacts against the proximal scutum within the fetlock canal when the fetlock overextends Highest compressive force on the DDFT in the foot occurs over the proximal border of the navicular bone so this is another common site for intrabursal tendon tears on the tendon's dorsal border in the forelimb

Percutaneous Tendon INjury

A tendon laceration usually requires the tendon to be taut during the impact

Phases of Tendon Repair

Acute Inflammatory Phase

Subacute Reparative or Fibroblastic Phase

Remodeling Phase

Acute Inflammatory Phase of Tendon Repair

Begins with the onset of clinical injury

Characterized by intertendinous hemorrhage, increased blood supply and edema, infiltration of leukocytes, initially neutrophils, followed by microphages and monocytes, and the release of proteolytic enzymes

Designed to remove damaged tendon tissue but thought to be excessive, further damaging the tendon

Lasts 1-2 weeks, but persists at a subclinical level

Subacute Reparative or Fibroblastic Phase of Tendon Repair

Begins a few days after onset of injury, overlaps with the inflammatory phase

Characterized by a strong angiogenic response and the accumulation of fibroblasts within the damaged tissue, which are responsible for synthesizing the scar tissue

Invading fibroblasts are larger and more basophilic and have large vesicular nuclei when compared to normal tenocytes More similar to myofibroblasts than tenocytes

Scar tissue has a higher collagen III content (20-30% compared to

Remodeling Phase of Tendon Repair

Reparative phase merges with the remodeling phase

Gradual but incomplete transformation to a higher proportion of type I collage as the scar tissue matures

New collagen fibrils become thicker, crosslinks increase in number and mature, and fiber alignment improves

Large amounts of fibrous tissue are laid down within and around the tendon, giving rise to a tendon that is persistently enlarged and strong but has greater structural stiffness Increase in stiffness reduces the efficiency of the tendon as a spring Increased stiffness results in increased strain rates in adjacent and relatively undamaged regions of the tendon which are then more prone to injury

Origin of Cells Involved in the Tendon Repair Process

Initially fibroblasts and inflammatory cells from the tendon periphery, blood vessels, and circulation are recruited to the injury site, thereby contributing to cellular infiltrate

Then intrinsic cells from the endotenon are activated as they migrate and proliferate at the injury site, recognizing the extracellular matrix and giving support to the internal vascular network

Growth Factors and Cytokines Involved in Tendon Healing

TGF-B

Basic fibroblast growth factor (bFGF/FGF2)

Insulin-like growth factor (IGF)-1

Vascular endothelial growth factor (VEGF)

Bone morphologic protein (BMP)

Growth and differentiation factor (GDF)

Epidermal growth factor (EGF)

Platelet-derived growth factor (PDGF)

TGF-B in Tendon Healing

Recruits fibroblasts and macrophages to the site of injury and induces increased proliferation, angiogenesis, and upregulation of MMP inhibitors and collagen expression as well as downregulation of proteinase activity

Connective tissue growth factor (CTGF) is a downstream mediator of TGF-B1 signaling and acts as a cofactor in fibrosis

Basic Fibroblast Growth Factor in Tendon Healing

Found in early wound healing

Has a role in fibroblast chemotaxis, proliferation, and angiogenesis

Epidermal Growth Factor in Tendon Healing

Role in regulating cell growth, proliferation, and differentiation

When is the optima baseline ultrasound for the severity of tendon injuries performed?

Approximately 1 week after the onset of injury

Ultrasonographic Characterization of Acute Tendon Pathology

• Acute tendon pathology is characterized ultrasonographically by enlargement, hypoechogenicity (focal or generalized), reduced striated pattern in the longitudinal images, and changes in shape, margin, or position

Ultrasonographic Characterization of Chronic Tendinopathy

• Chronic tendinopathy is associated with variable enlargement and echogenicity (often heterogenous and with retained echogenicity on off-incidence views when the transducer is tilted 5-10 degree), and an irregular striated pattern, which indicated fibrosis

Computerized Ultrasonographic Tissue Characterization (UTC)

• A high-frequency ultrasonographic probe, fixed in a transverse position, is moved along the long axis of a tendon by a precision instrument at a constant speed

• Contiguous transverse images are stored at real time and compounded in a 3D ultrasonographic data bloc

Additional Information Provided by Molecular Markers for Tendon Injury

• May offer additional information over traditional clinical examination and imaging by providing

  • A diagnosis when other tests are negative

  • Screening as part of a preventative strategy; early detection may enable introduction of measures (e.g. altered training) to minimize the risk of a career-ending injury

  • An objective assessment of the severity of the pathology and therefore helping to determine prognosis

  • Staging of the disease process, optimizing rehabilitation protocols

  • Choices of treatment and an objective assessment of their efficacy

Molecular Markers for Tendon Injury

• Initial investigations assessed markers of both collagen I synthesis (carboxy-terminal propeptide of type I collagen [PICP] and degradation (crosslinked carboxy-terminal telopeptide of type I collage [ICTP]) after tendon injury (Jackson, Smith, and Price, 2003)

  • Tendinopathy resulted in a significant rise in PICP concentrations, whereas ICTP concentrations were not different from those in the control group

  • Serum concentrations of PICP are able to reflect changes in type I collagen formation in healing connective tissue in one area of the body

  • Confirm that PICP is not an entirely bone-specific marker

• COMP is another candidate marker because it is abundant in young flexor tendon

  • Synovial fluid levels were more than tenfold higher than serum levels and have been shown to be significantly elevated in the synovial fluid from the digital flexor tendon sheath in cases of intrathecal tendon and ligament tears

  • In older horses, increased levels of COMP within the DFTS synovial fluid appeared to be strongly suggestive of the presence of a tear even when there is no evidence of this ultrasonographically

  • Serum COMP levels were not significantly elevated with tendon disease because of the relatively high natural levels of COMP in blood

Clinical Characteristics of SDFT Strain-Induced Injuries

• May be focal or generalized

• One of the more common manifestations is a central region of injury ("core lesion")

• Usually most severe level is centered just below the mid-metacarpal region, but frequently extends throughout most of the length of the metacarpal extrasynovial tendon and gives rise to swelling on the palmar aspect of the metacarpal region ("bowed" limb)

• Regions of the SDFT enclosed with in a tendon sheath (carpal sheath proximally, tendon sheath distally) are much less often affected

• Injury to branches of the SDFT in the pastern region results in abaxial swelling with pain on palpation and ultrasonography may be necessary to distinguish injuries of the oblique distal sesamoidean ligaments and palmar ligaments of the proximal interphalangeal region

Clinical Characteristics of Strain-Induced Injuries of the Accessory Ligament of the DDFT

• May occur as an isolated injury or in conjunction with SDF tendinopathy

• Lameness is often mild or absent

• Swelling restricted to the proximal half of the palmar metacarpal region, immediately dorsal to the SDFT and is usually more evident laterally

Clinical Characteristics of DDFT Strain-Induced Injuries

• Most frequently injured within the DFTS or navicular podotrochlear bursa

Clinical Characteristics of SDFT Lacerations

• MCP/MTP joint is hyperextended (dropped) when limb is loaded

Clinical Characteristics of SDFT+DDFT Lacerations

• MCP/MTP joint is hyperextended (dropped) when limb is loaded

• Toe is raised from the ground

Clinical Characteristics of SDFT+DDFT+SL Lacerations

• Complete loss of support of the MCP/MTP joint which is hyperextended to the extent that the MCP/MTP joint contacts the ground during the stance phase

Cold Therapy for Tendon and Ligament Injuries

• Important in acute inflammatory phase

• Antiinflammatory and analgesia, largely through ability to increase vasoconstriction, decrease enzymatic activity, reduce the formation of inflammatory mediators, and slow down nerve conduction

• Recommended not to apply cold therapy for longer than 30 minutes as prolonged exposure to cold temperatures can cause a reflex vasodilation, which can accentuate tissue swelling and edema

Compression and Coaptation for Tendon and Ligament Injuries

• In the acute phase of injury, pressure applied to the affected limb reduces inflammation and edema by increasing interstitial hydrostatic pressure

• With severe injuries when there is hyperextension of the MCP joint, a palmar/plantar splint of cast can be applied or a specially designed support boot can be used

Shoeing for DDFT Injuries

• Raising the heels reduces the tension in the DDFT (and ALDDFT)

  • Short-term management strategy for DDFT tendinopathy and desmitis of the ALDDFT because there is equilibration of forces in the supporting tendons and ligament in time and the heels need to be lowered at a later point to prevent heel collapse

  • Should be avoided for primary supporters of the MCP/MTP joint (SDFT and SL injuries) as the lowering of tension in the DDFT may increase loads in those structures

Shoeing for SL Injuries

• Increasing the palmar/plantar support of the hoof with a shoe with an extended length or increased width at the heels or egg bar shoe is often advocated for SL desmopathy, but raising the toe or fitting the shoe with a wider width in the toe region so it sinks less than the heels in soft ground can also be considered

Controlled Exercise for Tendon and Ligament Injuries

• Most SDFT, DDFT, and collateral ligament of the DIPJ injuries require up to 12 months of rehabilitation before resumption of full athletic function but some require up to 18 months

• SL desmitis can usually be rehabilitated within 6-9 months

• ALDDFT injuries can usually be rehabilitated within 3 months

• Increase in tendon CSA of greater than 10% between examinations suggests a degree of reinjury and the exercise level should be reduced

• In 28 Thoroughbred racehorses with SDFT tendinopathy 71% with a controlled exercise program returned to racing compared with only 25% managed with uncontrolled turnout (Gillis, 1997)

Extracorporeal Shock Wave Therapy for Tendon and Ligament Injuries

• Mechanism of action is unclear but is most likely related to induction of analgesia through an effect on sensory nerves

• Investigation of ECSWT as a treatment for chronic SL desmopathy resulted in 41% of hind limb patients returning to full work within 6 months of diagnosis (Crowe et al, 2004) compared with the previously reported 13% for conservatively managed cases (Dyson, 1994)

Therapeutic Ultrasound for Tendon and Ligament Injuries

• Thought that the main effect of ultrasound is conversion of sound energy into thermal energy

• In experimentally split equine tendons, therapeutic ultrasound resulted in increased vascularization and fibroblastic proliferation compared with controls (Morcos and Aswad, 1978)

Therapeutic Laser for Tendon and Ligament Injury

• Low-level laser therapy has been shown to stimulate cellular metabolism and to enhance fibroblast proliferation and collagen synthesis in vitro (Henninger, 1994)

Counter-Irritation for Tendon and Ligament Injury

• Studies have shown that there are no histologic differences between the collagen arrangement in the scar in cases of tendinopathy treated with firing and that of the controls (Silver et al, 1983)

• Firing is not an effective treatment for tendon and ligament injuries

When can intralesional treatment be considered for tendon and ligament injuries?

• Intralesional treatment should not be administered until 3 days after the injury because there is potential to increase hemorrhage

Intralesional Medication for Tendon and Ligament Injury - PSGAGs

• Inhibit collagenases and metalloproteinases and inhibit macrophage activation

• Have no effect on fibroblast synthesis

• Viewed as a soft tissue antiinflammatory agent

• In one study, treatment with PSGAGs either intramuscularly or intralesionally resulted in 76% of horses returning to work versus 46% of control animals, although these results were not stastically significant (Marr et al, 1993)

• Another study demonstrated improved echogenicity of collagenase-induced superficial digital flexor tendinopathy treated with intralesional PSGAGs with faster resolution of core lesion (Redding, Booth, and Pool, 1992)

• Another study demonstrated no significant difference in reinjury rates between horses treated with PSGAGs and those treated with controlled exercise alone (Dyson, 2004)

Intralesional Medication for Tendon and Ligament Injury - HA

• Consists of repeating units of D-glucuronic acid and repeating units of N-acetyl-D-glucosamine and is a component of tendon matrix

• Study showed no significant difference between the reinjury rates of horses with a superficial digital flexor tendinopathy treated with intralesional HA and those treated conservatively (Dyson, 2004)

• In a study of collagenase-induced digital flexor tendinopathy, HA was found to minimize tendon enlargement compared with controls, although histopathologic examination of the tendons failed to demonstrate a significant difference in the degree of inflammation (Gift, Gaughan, and DeBowes, 1992)

• Peritendinous HA has been shown to have no effect on ultrasonographic or histologic appearance, biomechanical properties, or molecular composition of tendons in collagenase-induced tendinopathy compared with controls, although it did appear to reduce lameness

• HA has been shown to decrease the extent of adhesions when administered intrathecally to treat collagenase-induced DDF tendinopathy within the digital sheath

  • Horses treated with intrathecal HA showed decreased inflammatory cell infiltrate and less intratendinous hemorrhage than controls

Intralesional Medication for Tendon and Ligament Injury - Methylprednisolone

• Methylprednisolone injected into and around normal equine tendons has been shown to cause dystrophic tissue mineralization and tissue necrosis

IGF-1 for Tendon and Ligament Injury

• Stimulates extracellular tendon matrix synthesis and is a potent mitogen

• In collagenase-induced models of tendinopathy, initial swelling was decreased after intralesional injections of IGF-1 compared with controls, although no differences were found at later time points and there was no difference between the quantities of type I and type III collagen synthesized

• In a study assessing the efficacy of IGF-1 in natural disease, there appeared to be no significant benefits over other treatments

rEGH for Tendon and Ligament Injury

• rEGH administered intramuscularly has demonstrated a negative effect on some of the biomechanical properties (decreased yield point and ultimate tensile strength) of the SDFT during the early phases of healing in collagenase-induced tendinopathy, although elasticity was maintained

TGF-B for Tendon and Ligament Injury

• Horses treated with TGF-B1 showed significant enlargement of the tendon and although reinjury rates were similar to those in conservatively managed horses, these reinjuries were all on contralateral, untreated limbs

PRP for Tendon and Ligament Injury

• Has been demonstrated to enhance the expression of collagen genes 1A and 3A and COMP in equine SDFT explants with no associated increase in MMP3 or MMP13

• In a randomized, prospective clinical trial on a limited number of naturally occurring superficial digital flexor tendinopathies, a single intralesional PRP treatment contributed to an earlier reduction of lameness and to an advanced organization of the repair tissue compared with intralesional saline injection as a control (Geburek et al, 2016)

ACS (IRAP) for Tendon and Ligament Injury

• A study found no significant difference in GAG, COMP, or type I collagen between normal equine serum and ACS treated tendon explants (Dahlgren and Harvey, 2008)

• A clinical trial in horses with acute tendinopathies of the SDFT revealed a significantly faster reduction of lameness and a temporary improvement of ultrasonographic parameters in the ACS-treated group compared with controls (Geburek et al, 2015)

• A cases series of 272 horses treated with ACS for proximal suspensory desmopathy reported a high success rate combined with a shortened convalescence period, but only included cases with no or only minor fiber disruption, and provided no control group (Easter and Watts, 2014)

MSCs for Tendon and LIgament Injury

• Standard cell dosages for the treatment of a SDFT core lesion are ~50 million for minimally manipulated preparations and !20 million for culture preparations and these are delivered intralesionally

• Using scintigraphy, the distribution of hexamethyl propylene amine oxime (HMPAO) and Tc99m labeled allogenic bone marrow-derived MSCs after intraarterial (median artery) and intravenous (cephalic vein) regional limb perfusion was evaluated in healthy horses (Sole et al, 2012)

  • In contrast to intravenous RLP, distribution of labeled MSCs through the entire distal limb was achieved with intraarterial RLPS but severe arterial thrombosis occurred in 1/6 horses

  • Median persistence of MSCs was 39% and 28% at 6 hours and 29% and 16% at 24 hours following intraarterial and intravenous injection, respectively

  • Utilizing the same technique in experimentally induced lesions (Sole et al, 2013) and in naturally occurring injuries (Becerra et al, 2013), similar levels of cell retention of only 24% after 24 hours following intralesional treatment were observed in both studies

    • In naturally occurring injuries, focal uptake was evident at the site of injury in all horses after intralesional injection of labeled cells, with 4/13 horses displaying diffuse or focal uptake of radiopharmaceutical within the lung field immediately after implantation

    • Immediately after IVRLP, focal uptake at the site of injury was evident in 75% of horses

    • Cell retention was only 32% and 9% at 12 hours after intralesional injection and RLP, respectively

• Stem cell-treated racehorses showed a 50% reduction in reinjury rate compared with historical controls selected and followed up in identical fashion

Indications and Contraindications for Tendon Splitting

• Not recommended for chronic cases due to extensive granulation tissue formation, increased trauma to the tendon tissue, and persistent lameness after treatment

• Some advocate use for management of acute cases when there is an anechoic core lesion in order to decompress the core lesion by evacuating the serum or hemorrhage and to facilitate vascular ingrowth. Removal of the fluid in the core lesion may also reduce proximodistal propagation of the lesion

• In a collagenase-induced model of tendinopathy in six horses, tendon splitting using the knife technique resulted in faster resolution of the core lesion and quicker revascularization of the lesion, and increased collagen deposition compared with untreated controls (Henninger, Bramlage, and Bailey, 1992)

Tendon Splitting Technique

• Can be performed under standing sedation or general anesthesia

• Can be done blindly or using ultrasonographic guidance which reduces damage to nromal tendon tissue

• #11 scalpel blade or double-edged blade is inserted into the tendon and "fanned" proximad and distad

• The procedure can also be achieved with multiple insertions of a 23-gauge needle, possibly with less damage to the remaining, relatively intact tendon tissue

• After tendon splitting has been performed, a modified Robert Jones bandage should be applied and the horse rested in a stall for 10-14 days, after which a slow progressing exercise program should be initiated

Goal of Desmotomy of the Accessory Ligament of the SDFT

• First described as treatment for SDFT tendinopathy

• Aim is to produce a functionally longer musculotendinous unit to reduce strain on the SDFT

• Transected accessory ligament heals within 60 days but measures approximately 2 cm longer than preoperatively

• Has been shown in equine cadaver models that DALSDFT actually increases the strain on the SDFT during loading because of increased extension of the MCP joint

• Increased risk of injury of the SL after DALSDFT has also been demonstrated in vivo

• A recent retrospective published positive results with 69% of Thoroughbred racehorses with SDFT tendinopathy treated by DALSDFT returning to racing (Hu and Bramlage, 2014)

  • 70% raced more than five times after surgery

  • Horses older than 4 years were significantly less likely to return to racing than younger horses

Desmotomy of the Accessory Ligament of the SDFT Technique

• Can be performed via an open medial approach or tenoscopically through the carpal sheath

  • Horse in dorsal or lateral recumbency

  • Affected limb partially flexed, carpal sheath distended

  • Tenoscopic portal into the carpal sheath created 2-3 cm proximal to the distal radial physis on the lateral side of the limb between the ulnaris lateralis and lateral digital extensor muscles

  • Instrument portal is made immediately proximal to the distal radial physis

  • Probe used to palpate the distal and proximal limit of the subsynovially located accessory ligament which is transected directly over the flexor carpi radialis tendon using a #10 scalpel blade on a long handle, menisectomy knife, or a tenotomy knife

  • The very proximal portion of the ligament cannot be visualized directly because it extends proximad to the synovial reflection of the carpal sheath

  • For the proximal portion, careful dissection using punch biopsy forceps is needed, taking care to avoid the perforating blood vessel at the proximal limit of the accessory ligament

  • Transection can also be performed using electrosurgical instruments such as loop-headed or hook-headed monopolar electrodes or bipolar radiofrequency probes

    • Main benefit is reduction of intrathecal hemorrhage

Desmotomy or Desmectomy of the Accessory Ligament of the DDFT

• Conservative management of accessory ligament of the DDFT (ALDDFT) desmopathy is usually successful

• In some cases desmopathy recurs or causes adhesions between the ALDDFT and the SDFT which can result in a flexural deformity

  • In these cases desmotomy or desmectomy may be considered

• Open approach or less invasive techniques which utilize either ultrasonographic guided transection of the ALDDFT or a tenoscopic technique, utilizing a distomedial approach into the carpal sheath at the level of the junction between the middle and proximal third of MCIII and a contralateral instrument portal and the same level

Palmar/Plantar Annular Ligament Desmotomy Indications

• PAL desmotomy is indicated when there is a relative constriction of the PAL in the DFTS, impeding the normal gliding function of the flexor tendons causing lameness that does not respond to conservative management

• Logical to only transect the PAL if it is causing a clinical problem as second-look arthroscopies have identified adhesions to the site of the PAL transection, but a recent study revealed a trend for improved outcome if PAL desmotomy was performed in addition to tenoscopic debridement

• Best performed tenoscopically to assess the digital sheath for primary pathology but can also be achieved via an open approach or a limited open incision

Open Approach for Palmar/Plantar Annular Ligament Desmotomy

• Performed under general anesthesia in lateral recumbency

• Paramedian skin incision extends over the entire length of the PAL slightly abaxially to the palmar/plantar midline

• Dissection through the subcutaneous tissue is directed towards the palmar/plantar midline to allow transection of the PAL at the level of the mesotenon and division of adhesions if required

• Routine closure of subcutis and skin

• Disadvantages: need for general anesthesia and risk of wound dehiscence, with potential further complications such as septic tenosynovitis

Limited Open Approach for for Palmar/Plantar Annular Ligament Desmotomy

• Where only the PAL is affected, the limited open approach can be used

• 1-2 cm long skin incision at the proximal border of the PAL and transection of the ligament with a curved bistoury or a scalpel blade guided by a curved instrument or a groove director

• Can be performed in the standing animal but does not allow resection of adhesions or comprehensive assessment of the DFTS

Tenoscopic Transection of the Palmar/Plantar Annular Ligament

• Preferred because it is less traumatic, ensure accurate transection of only the PAL, and allows evaluation of the tendons to identify any primary causes

• Performed via standard tenoscopic approach and is most easily performed using a hooked knife introduced via a proximal portal and guided to the distal end of the PAL under tenoscopic control to ensure it does not pass through the manica flexoria

• Can also be performed using a slotted cannula by introducing the cannula through a proximal instrument portal and passing it out of the scope portal

• A radiofrequency probe can also be used which allows precise transection and reduces hemorrhage

Indications for Digital Flexor Tendon Sheath Tenoscopy

• The DDFT is more commonly affected than the SDFT in the forelimb, whereas tears to the manica flexoria of the SDFT are more frequently found in the hind limbs

• Intrathecal tears of the DDFT are most commonly directed longitudinally and located at the periphery of the tendon, usually laterally

• A survey further specified that most DDFT tears are long (>7 cm), extending from the proximal aspect of the DFTS distally to the PAL, and superficial (<5 mm deep)

• On study showed 63% sensitivity and 75% specificity of ultrasonography to identify longitudinal tears of the flexor tendons in the DFTS (Arensburg et al, 2011)

• Contrast radiography has a sensitivity of 96% to detect tears of the manica flexoria and sensitivity of 57% to find marginal tears of the DDFT. The specificity for both types of lesions is approximately 80%

• Tears of the manica flexoria are most commonly located at the medial attachment of the manica flexoria to the SDFT

• Standard tenoscopic portal is located slightly palmar/plantar of the center of the outpouching between the PAL and the proximal digital annular ligament, adjacent and palmar/plantar to the neurovascular bundle, and just distal to the PAL

• All tears of the manica flexoria should be treated by complete tenoscopic resection, since debridement has been associated with poor outcome

Tenoscopic Resection of the Manica Flexoria

• PAL desmotomy can be performed first if necessary for ease of movement of surgical instruments

• In the lateral recumbency approach where portals need to be created ipsilaterally, the lateral border of the MF is transected first using a #12 scalpel blade or 14 gauge needled inserted through a second instrument portal located laterally at the level of the distal end of the manica flexoria, between the DDFT and SDFT

• A third instrument portal is created in the proximal part of the DFTS to introduce a rongeur to grasp the distal and lateral edge of the manica flexoria and apply tension which rolls the SDFT medially and allows resection of the medial border of the manica flexoria dorsad to the DDFT using arthroscopic scissors, a hook knife, 14 gauge needle, or biopsy punch instruments

• When in dorsal recumbency, the manica flexoria can be severed from its attachment to the SDFT on each side of the limb using a hook knife introduced via biaxial proximal instrument portals, ensuring the blade is introduced under the manica flexoria (so the hook knife points abaxially to avoid iatrogenic damage to the DDFT) and is aligned in the same plane as the border of the SDFT

• The manica flexoria is withdrawn from one of the proximal instrument portals having transected the remaining synovial attachments to its proximal border

Digital Flexor Tendon Sheath Tenoscopy Aftercare

• Horse should be rested for at least 2 weeks after which handwalking can be started at 5 minutes/day, increasing by 5 minutes/week for at least 6 weeks

Digital Flexor Tendon Sheath Tenoscopy Prognosis

• Prognosis for a successful outcome defined as soundness and return to previous level of activity is better for patients treated with tenoscopic removal of the manica flexoria (~80% success rate) than for tears of the flexor tendons (~40% success rate)

Digital Flexor Tendon Sheath Synoviocoeles

• Not all synoviocoeles are significant, the ones that do not decompress when the limb is lifted are more likely to be significant

  • If significant, can be resected via an open approach and the defect in the DFTS carefully sutured to avoid recurrence or have also been successfully treated by enlarging the opening to the synoviocoele using a synovial resector

Approach to the Carpal Sheath

• Horse in dorsal or lateral recumbency

• Affected limb partially flexed, carpal sheath distended

• Tenoscopic portal into the carpal sheath created 2-3 cm proximal to the distal radial physis on the lateral side of the limb between the ulnaris lateralis and lateral digital extensor muscles