Functional Anatomy, Histology and Biomechanics of the human Achilles Tendon – a comprehensive review

Journal Pre-proof Functional Anatomy, Histology and Biomechanics of the human Achilles Tendon – a comprehensive review Kamil Winnicki, Anna Ochała-Kłos, Bartosz Rutowicz, Przemysław ˛ A. Pekala, Krzysztof A. Tomaszewski

PII:

S0940-9602(20)30004-2

DOI:

https://doi.org/10.1016/j.aanat.2020.151461

Reference:

AANAT 151461

To appear in:

Annals of Anatomy

Received Date:

7 June 2019

Revised Date:

12 November 2019

Accepted Date:

7 January 2020

˛ Please cite this article as: Winnicki K, Ochała-Kłos A, Rutowicz B, Pekala PA, Tomaszewski KA, Functional Anatomy, Histology and Biomechanics of the human Achilles Tendon – a comprehensive review, Annals of Anatomy (2020), doi: https://doi.org/10.1016/j.aanat.2020.151461

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Functional Anatomy, Histology and Biomechanics of the human Achilles Tendon – a comprehensive review

Kamil Winnicki1, Anna Ochała-Kłos1, Bartosz Rutowicz1, Przemysław A. Pękala1, Krzysztof A. Tomaszewski2,3

Department of Anatomy, Jagiellonian University Medical College, Krakow, Poland

2

Faculty of Medicine and Health Sciences, Andrzej Frycz Modrzewski Krakow University,

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Scanmed St. Raphael Hospital, Krakow, Poland

*Corresponding Author:

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Krzysztof A. Tomaszewski MD, PhD, DSc

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3

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Krakow, Poland

Department of Orthopaedics, Trauma and Rehabilitation

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Faculty of Medicine and Health Sciences

Andrzej Frycz Modrzewski Krakow University 1 Gustawa Herlinga-Grudzinskiego Street 30-705 Krakow, Poland

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e-mail: [email protected]

Abstract:

Objectives

The aim of this study was to provide a comprehensive overview of the anatomical, histological, and biomechanical aspects of the Achilles tendon.

Methods A comprehensive search on the relevant aspects of the Achilles tendon was performed through the

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main electronic databases up to October 2019. Data from relevant articles was gathered, analyzed,

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and included in this review.

Results

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This review outlines crucial topics on the anatomy, histology, and biomechanics of the Achilles

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tendon. The first part, focusing on clinically relevant anatomy, describes the tendon as well as its surrounding structures. Particular focus is made on anatomical divisions. The second part discusses

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histologic features, contrasting normal morphology with pathologic changes. The third part summarizes various biomechanical aspects of the Achilles tendon, especially those crucial to

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understanding the key functionality of the tendon. These components make up this review aimed to aggregate relevant information regarding the Achilles tendon to provide an up to date assessment of current knowledge, as well as visions for future directions of Achilles tendon

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research.

Conclusions

Comprehensive knowledge regarding the Achilles tendon is crucial whilst rates of injury continue to be relevant. A proper understanding of the anatomy, histology, and biomechanics is vital for clinical perception as well as establishing the direction of further research in new therapies.

Keywords: Achilles tendon, histology, biomechanics, anatomy, rupture 1. Introduction The Achilles tendon (AT) [Figure 1] is a well-studied structure that permits foot plantar flexion. The calcaneal tendon was given its informal name in 1693, alluding to the death of the

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semi-immortalized Greek god Achilles who was killed by a poisoned arrow in this area (Klenerman, 2007).

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With the number of ruptures in North America up to 9.9 per 100,000 (Suchak et al., 2005), and rates of tendinopathy in adults as high as 2.35 per 1,000 (De Jonge et al., 2011), risk factors

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such as high obesity rates have driven a demand to develop a better understanding of AT

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biomechanics (Abate et al., 2012). Characterized by pain, swelling, and diminished performance of the tendon, Achilles tendinopathy continues to remain of clinical relevance, driving forward

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prospects in new potential therapies (Maffulli et al., 2015). There has also been a push for a better anatomical understanding to facilitate the development of less invasive surgeries to minimize

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nerve damage and shorten recovery time (Bhattacharyya and Gerber, 2009). As a result, a deeper understanding of AT microcirculation and innervation have increased in relevance, especially for explanations of surgery-related complications. Improved imaging techniques in parallel with computer modeling have given new insights into the biomechanical motion that makes the AT

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vulnerable to injury (Franz and Thelen, 2016; Handsfield et al., 2017). All of these contributing elements interplay during consideration of conservative versus surgical treatment in AT injury, and the importance of anatomic knowledge is paramount in developing improved techniques and approaches. Despite the last decade’s countless advances in study techniques and a considerable amount of research, many aspects of the AT still remain untouched.

The aim of this review is to present the current state of knowledge on the functional anatomy, histology, and biomechanics of the human AT, and relate it to possible future investigations and clinically important translational research.

2. Anatomy

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2.1 Muscles The muscles that contribute to the AT are located in the posterior compartment of the

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anatomical leg and comprise the calf muscle. The most superficial muscle connected to the AT is the gastrocnemius. This muscle is built of a medial and lateral head that connect to each other in

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the midline of the posterior compartment (O’Brien, 2005). Immediately inferior to the

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gastrocnemius in most individuals is the plantaris muscle. While not usually part of the AT, it has been found to invaginate within the AT and is a source of mid-Achilles tendinopathy (Spang et al.,

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2013). Anterior to the plantaris lies the soleus. While identical in function to the gastrocnemius, it contains different muscle fibers (Gollnick et al., 1974). The general name for soleus and the two

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heads of gastrocnemius is triceps surae. The tendon is formed by fascicles from this triceps and is rotated within the lower leg (Pekala et al., 2017). The medial head of the gastrocnemius forms a more posterior layer of fibers while the lateral head contributes anterior fibers. Fibers from the soleus compose the central and medial areas, providing a secondary contribution to the tendon

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(Szaro et al., 2009) [Figure 2].

2.2 Muscle Attachments The lateral and medial heads of the gastrocnemius originate on the lateral and medial

femoral condyles, respectively, while the soleus originates on the upper fibular head and on the

soleal line of the tibia. Both insert into the calcaneus via the Achilles tendon (O’Brien, 2005). The insertion of the tendon to the calcaneus is in a crescentic shape corresponding to the posterior calcaneal prominence with a radius ranging between 13.8 and 43.6 mm. Furthermore, there are extensions to the lateral and medial calcaneal surfaces that average distances between 1 and 3.5 mm (Lohrer et al., 2008). The actual location of the musculotendinous junction as compared to the

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point of distal attachment on the calcaneal tuberosity varies, and may be assessed by measuring the distance between the two. Pichler et al found that 12.5% of cases have a distance of 0-2.54 cm,

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70% of cases have a distance of 2.54-7.62 cm, and 17.5% of cases have a distance greater than 7.62 cm. Importantly, the soleus muscle may extend more distally than the beginning of the tendon

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and may appear as an incomplete rupture (Pichler et al., 2007).

2.3 Tendon Anatomy

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To increase specificity when describing disorders, detailed naming for each part of the tendon was proposed in 2013. Beginning at the calcaneus is the calcaneal insertion, followed

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superiorly by the pre-insertion site, about 2 cm above the calcaneus. The non-insertional region, containing the mid-portion of the tendon, supersedes this pre-insertion site. Classification for sagittal MRI scans was proposed, naming the most superior part encompassing muscle tissue as the intramuscular part. This is followed by a free tendinous region, and most distally, a calcaneal

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section. The free tendinous part is further divided into proximal, middle, and distal regions (Del Buono et al., 2013). The location at which the tendon inserts into the calcaneus is protected by the heel fat pad (HFP). The HFP is on average 1.43 mm thick and lies behind the plantar tuberosity (Campanelli et al., 2011). Damage to this pad has been associated with achillodynia (Jorgensen, 1985). In order to image the anatomy of the tendon, freehand 3D ultrasound has been used to

provide accurate length, volume, and cross sectional area. This data is accurate in vivo under both, load or static conditions (Steven J. Obst et al., 2014).

2.4 Circulation The posterior compartment of the leg is traversed medially by the posterior tibial artery

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(PTA) and laterally by the peroneal artery (PA). The proximal and distal portions of the tendon are supplied by the PTA while the midsection is supplied by the PA. Attributed to the large number

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and caliber of arteries, the anterior surface of the AT is considerably better vascularized than the posterior surface of the AT, where the vessels go through or around the tendon. The vessels within

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the AT run in three main directions: longitudinal, transverse, and deep. The superficial transverse

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vessels are the biggest in size and give a large number of longitudinal branches which are parallel to the tendon's fibers. Torsion of AT fibers may cause rotation of the tendon's vessels (Chen et al.,

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2009). Yepes et al. used angiography following an injection of lead-oxide, gelatin, and water to further describe the vasculature. Three vascular zones of the skin covering the AT were elaborated:

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a medial zone with the richest vascularization, a posterior zone with poor circulation, and a lateral zone where blood supply is worse than within the medial zone, but better than the posterior. With this in mind, surgeons should plan skin incisions in the medial and lateral zones to improve healing of the wound after AT surgery (Yepes et al., 2010). Diminished vasculature in the midsection was

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described by Chen in 2009, and this area was believed to be more vulnerable to damage (Chen et al., 2009) [Figure 3, 4]. Wolff et al., using angiography to eliminate methodological errors, studied the anterior tibial (TA) and posterior tibial (PTA) arteries, concluding that avascularization may be detected due to methodological differences as a result of the small diameter of the arteries. The

results of their study characterized a dense net of five small arteries carrying blood from the TA and seven from the PTA into the paratenon region (Wolff et al., 2012). Apart from the larger vessels, the microcirculation of the Achilles tendon can also play a role in the etiology of AT tendinopathy. Neovascularization of the microcirculation in the Achilles tendon has been closely associated with tendinopathy. The cause of this angiogenesis, regulated

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by endostatin, may have varying sources. These changes, further leading to growth of neural fibers and inflammation, may cause pain symptoms in patients suffering from AT tendinopathy

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(Knobloch, 2008). Tendons affected by tendinopathy have increased blood flow which may be detected by ultrasonographic imaging (Astrom, 2000; Kristoffersen et al., 2005; Reiter et al., 2004;

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Zanetti et al., 2003). A recent study using contrast enhanced ultrasonography has shown

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improvements in detection of neovascularization as compared with power Doppler sonography, although it did not find correlation between pain and disability with detection of

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neovascularization. The authors, however, concluded that an ability to differentiate between arterial and venous neovessels could provide greater understanding of the specific effects of new

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vessels in vivo, a future direction in this subject (De Marchi et al., 2018). Variable vascularization of the mid-portion of the tendon may play a crucial role in the AT's rupture, and these variations may contribute to differences in the mechanical durability of the AT (Chen et al., 2009; Pedowitz and Kirwan, 2013; Wolff et al., 2012). Tendon repair, however,

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is strongly associated with the development of small vessels and is impossible without it. Wolff et al. reported that the use of extracorporeal shockwave treatment with unfocused ultrasound can improve healing (Wolff et al., 2012). More studies, such as those using immunohistochemical techniques, are needed to determine the precise scope of the microvasculature of the AT, albeit being limited to in vitro conditions. Enhanced imaging techniques such as microtomography could

also be used to characterize a more decisive three-dimensional network of capillaries and how it differs in various states, such as comparing healthy ATs with those affected by tendinopathy. Such knowledge at a microscopic level could bring further understanding to the development of

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pathologic changes of the AT and how they may potentially be prevented.

2.5 Innervation

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The AT is innervated chiefly by nerve fibers originating from the sural nerve (SN). These also supply the skin on the distal posterolateral third of the lower extremity and the lateral part of

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the foot. The SN, also known as the short saphenous nerve, additionally gives off the lateral

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calcaneal branch which innervates the lateral aspect of the heel. The nerve is formed by the union of the medial sural cutaneous nerve, originating from the tibial nerve, and the peroneal

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communicating nerve, branching from the common peroneal nerve in the middle third of the leg. At a level 8-10 cm proximal to the superior border of the calcaneus, the SN passes the lateral

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border of the AT (Blackmon et al., 2013). The SN is thus at high risk for iatrogenic injury during surgeries performed on the AT. Disruption of this nerve may lead to sensory deficits, and awareness of its presence during procedures conducted on the AT is very important for surgeons in order to avoid subsequent paresthesia (Maes et al., 2006; Rebeccato et al., 2001). The path of

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the SN is closer to the AT in younger patients as compared to older, and they are at higher risk of nerve damage during surgical procedures. New studies recommend the use of intraoperative ultrasound examination to locate this critical structure and decrease the risk of iatrogenic injury. A recent study reiterated the usefulness of high-frequency, high resolution, real time ultrasonography probes for sural nerve visualization, which could be used either intraoperatively

or perioperatively to minimize the risks of nerve injury when undertaking percutaneous repair of Achilles tendon tears (Kammar et al., 2014; Zappia et al., 2018). Other actions that may diminish the risk of injury to the SN include choosing the distal 45% of the AT when placing sutures near the lateral side of the AT (Apaydin et al., 2009) and using a distal lateral portal for tendinoscopy when in contact with the AT, although the risk remains moderate and is also present in regards to

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the lateral calcaneal nerve (Appy-Fedida et al., 2015). The tibial nerve gives less supply to the AT but innervates the gastrocnemius and soleus. This nerve has a profundal location and as a result

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has a low risk of iatrogenic injury during surgeries performed on the AT. An understanding of the innervation of the AT is crucial to ensure proper maintenance of the integrity of the nerves and

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diminish possible injury during therapeutic intervention.

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The sensory receptors in the AT are comprised of Ruffini type 1 corpuscles for pressure sensitivity, type II Vater-Pacinian for movement, Golgi tendon organs that sense changes in

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tension, and free nerve endings for pain (Doral et al., 2010). Immunohistochemistry has located these nerve components to be closely associated with blood vessels in tendinosis tendons as well

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as paratendinous connective tissue (Bjur et al., 2005).

3. Histological Structure of Healthy and Pathological Achilles tendons

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All tendons in the human body have a similar histological structure. They are composed of

connective tissue which includes an extracellular matrix (ECM) that consists mostly of collagen and specialized cells termed tenocytes (Waggett et al., 1998). Collagen constitutes 65-80% of the dry mass of healthy tendons (Kannus, 2000). Collagen proteins may be divided by their features and properties. The collagens that form fibrils are composed of types I, II, III, V and XI. Forms of

collagen that are associated with fibrils include types IX, XII, XIV, and XIX - XXI. Hexagonal networks are created by type VIII and type X collagen, and microfibrils by type VI collagen (Tresoldi et al., 2013). The tendon’s basal membrane is composed of type IV collagen, whereas anchoring fibrils are provided by type VII collagen. In addition, tendons may have transmembrane proteins in the form of type XIII and type XVII collagen (Tresoldi et al., 2013).

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The Achilles tendon is composed of a typical connective tissue (Waggett et al., 1998) and has a hierarchical structure composed of type I collagen. It consists of fiber bundles, fascicles, and

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fibrils. Besides proteins, proteoglycans (PGs) make up a large part of the composition (Waggett et al., 1998). The basic PGs, which are connected to fibrils in the Achilles tendon, are decorin and

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fibromodulin (Franchi et al., 2007; Freedman et al., 2014; Longo et al., 2009; Waggett et al., 1998).

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Among the collagens, type I collagen comprises over 90% of a healthy Achilles tendon (Waggett et al., 1998). Besides type I collagen, the other major variant found is type III collagen,

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present not only in the tendon, but also within the fibrocartilage of the tendon. Considering the composition and distribution of collagen fibers in tendons, it can be concluded that their primary

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function is to guarantee tensile strength. Type V collagen forms the core of type I collagen fibrils and is involved in the regulation of the diameter of the fibers. Immunohistochemical research by Wagget et al. detected type II collagen in the attachment and fibrocartilage regions, but did not find any in the mid-tendon area (Waggett et al., 1998). With type I, II, and III collagen in mind,

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this confirms the intermediate character of this tissue, exhibiting properties of both dense fibrous connective tissue as well as hyaline cartilage (Benjamin and Evans, 1990). Fukuta et al. demonstrated the presence of type X collagen in the Achilles tendon, with its presence dominating the mineralized area (Fukuta et al., 1998). Type VI collagen was also observed widely throughout the central region of the tendon (as in fibrous tissue, within the ECM), and within the fibrocartilage,

although located around cells (Waggett et al., 1998). Therefore, it seems that type VI collagen helps fulfill different functions in these regions. Type VI collagen is thought to be involved in connecting cells with ECM molecules such as decorin, fibrillar collagen, and hyaluronate (Kielty et al., 1992). In fibrocartilage, tendon-bone junctions, and especially in mineralized regions, there are large quantities of type X collagen (Fukuta et al., 1998; Niyibizi et al., 1996). Because this type

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of collagen is characteristic for cartilage, its presence at the site of attachment of the Achilles tendon to the calcaneus may indicate that this area is cartilaginous by natural origin (Fukuta et al.,

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1998).

Besides collagen, it is believed that elastin provides mechanical properties of tendons

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despite only accounting for approximately 1% of the total wet weight (Henninger et al., 2013).

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Elastin, formed in the extracellular space, consists of a core in the form of tropoelastin molecules connected to a microfibrillary scaffold. Elastin fibers can stretch and contract, and are located

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along both the surface of collagen fibers and within their network, allowing for the repair of tissue after deformation (Henninger et al., 2013). High elastin content was additionally localized to the

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endotendinium in regions of primary collagen bundles (Gibson and Cleary, 1987). Proteoglycans (PGs) and non-collagenous glycoproteins may also be found in the matrix (Kannus, 2000). In addition to structural and regulatory functions, this matrix is also a transmitter of both biochemical and mechanical signals into tendon cells. They provide an integrated control

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of proliferation, differentiation, migration, and survival of tenocytes (Tresoldi et al., 2013). Proteoglycans give the extracellular matrix specific properties (Rigozzi et al., 2013; Waggett et al., 1998). The Achilles tendon does not contain large amounts of PGs, but both small and large proteoglycans have been detected (Rigozzi et al., 2009). Among the small PGs, the most abundant is decorin, which like the others proteoglycans from this group, extends along the entire length of

the tendon. Biglycan, fibromodulin, and lumican have been detected in both fibrocartilage as well as mid-tendon regions (Waggett et al., 1998). Their presence in the ECM influences the formation and regulation of a hierarchical construction of collagen (Hedbom and Heinegard, 1989). Large PGs include versican within the midtendon and aggrecan in fibrocartilage areas. In contrast, chondroitin sulfate, dermatan sulfate, and keratan sulfate were localized in both attachment areas

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and the central part of the tendon (Waggett et al., 1998). Versican, detected by monoclonal antibodies in sesamoid fibrocartilage and in the mid-tendon, was not identified in areas of

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fibrocartilage attachment. It has, however, been detected in these areas through the usage of immunohistochemistry. Versican, bound to hyaluronan, can adhere to tendon cells which may

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contribute to their motility, growth, and differentiation (LeBaron et al., 1992; Perides et al., 1992).

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It is believed to be synthesized in regions other than sesamoid fibrocartilage, while its incorporation takes place mostly within this structure (Waggett et al., 1998). Using western blot

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and immunohistochemistry, another large PG, aggrecan, was detected in sesamoid fibrocartilage and at points of fibrocartilage attachment in ATs (Waggett et al., 1998). Its general function is to

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provide resistance to compression (Corps et al., 2006). The presence of versican (characteristic to fibrotic tissue) and aggrecan (characteristic to cartilage) may explain the intermediate nature of the fibrocartilage (Waggett et al., 1998).

The ECM of the Achilles tendon also contains small amounts of non-collagenous

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glycoproteins which are constructed largely by protein and sugar residues. These proteins primarily include fibronectin, laminin, thrombospondin, and tenascin-C (Kannus, 2000). Fibronectin is a large glycoprotein occurring in blood vessel walls, chiefly in basement membranes. Cooperating with type IV collagen, it connects the basal membrane with the intracellular matrix. Fibronectin may also allow connective tissue to interact with type III collagen

(Jozsa et al., 1989). In a healthy Achilles tendon, fibronectin is localized in specific areas. Deposits of this glycoprotein have been observed in regions of connection between the tendon and muscles, especially in regions of rupture or degeneration (Jozsa et al., 1989). The results of histological and immunohistochemical studies have shown that fibronectin interacted more effectively with denatured collagen fibers than native collagen. The presence of large quantities of this glycoprotein

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within a tendon may be a symptom of connective tissue degeneration. Both laminin and fibronectin were found in large quantities within the myotendineal junction (Jozsa et al., 1989). Laminin, with

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type IV collagen, builds the basement membrane and the walls of blood vessels in connective tissue (Jozsa et al., 1989; Tresoldi et al., 2013). Its presence is used for the microscopic imaging

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of Achilles tendon vasculature (Zantop et al., 2003). The presence of laminin on the surface of

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intact basement membrane contributes to long-term stability. In addition, it participates in the regulation of tendon cell survival (Taylor et al., 2011).

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A related group of proteins are the thrombospondins (TSP), which are involved in the regulation of cell function and vascularization. They also influence interaction between the cell

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and proteins, and between proteins themselves in the extracellular matrix (Adams, 2001). Such TSP interactions with other components of the ECM give these glycoproteins the ability to influence motility, proliferation, apoptosis, and tenocyte response to various factors (Adams, 2001; Adams and Lawler, 2011). The main thrombospondin found in the tendon is the protein TSP-4,

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which is localized in the extracellular matrix and regulates its deposition. In addition, thrombospondin-4 is required to create the proper hierarchy of collagen fibers (Frolova et al., 2014). ATs also contain TSP-1(Kannus et al., 1998), TSP-5, and TSP-3, albeit in lesser quantity (Frolova et al., 2014; Kannus et al., 1998).

An equally important Achilles tendon glycoprotein, tenascin-C, is a hexameric protein containing disulfide (De Palma et al., 2004). Like other glycoproteins, tenascin-C is a component of the extracellular matrix. In immunohistochemical studies, a high reactivity of tenascin-C has been detected in the areas of connection between muscle and tendon, in the vicinity of the tendon cells themselves, and on collagen fiber surfaces. Significantly smaller quantities of this protein

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have been observed in the fibrocartilage at the junction of the Achilles tendon with the calcaneus (Kannus et al., 1998). Tenascin-C has the ability to act as an anti-adhesive, thus it may be involved

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in tenocyte adaptation to the compression force of mechanical stimuli (De Palma et al., 2004). Due to a lack of difference in tenascin expression in healthy and pathological ATs, this protein cannot

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be used as a satisfactory diagnostic marker (Pajala et al., 2009).

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Tenocytes and tenoblasts, classified as tendon cells, constitute 90-95% of cells within tendons. Synovial cells, chondrocytes, and vascular cells can also be found (Doral et al., 2010;

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Kannus, 2000; Tresoldi et al., 2013). During pathological conditions the tendon may also contain inflammatory cells such as macrophages and myofibroblasts (Kannus, 2000). In a newly

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developing tendon, the quantity of cells dominates the contents of the extracellular matrix. These cells are tenoblasts, arranged in a long, parallel chains, although in different shapes and sizes. They are primitive tendon cells having nuclei of various shapes ranging from oval to elongated. Characteristic structures of these cells include a very prominent Golgi complex and rough

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endoplasmic reticulum. This suggests an intense biosynthesis of protein. Pinocytotic vesicles, actin and myosin filaments, and lysosomes are present in the cytoplasm and are characteristic for tenoblasts (Kannus, 2000; Tresoldi et al., 2013). As the tendon matures, the ratio of cells to matrix changes. Tenoblasts produce components of the ECM and increase surface area while beginning to take on a spindle shape. In the adult tendon, long cells termed tenocytes are formed from

tenoblasts. They are characterized by an elongated nucleus, which extends through the whole length of the cell (Kannus, 2000). Tenocytes demonstrate organized cellular arrangement. In crosssection, they have a starry shape; in a longitudinal perspective, they are in parallel rows. In cases of tendinopathy or rupture of the Achilles tendon, tenocytes produce much more type III collagen, and

the

tendon

becomes

less

resistant

to

tensile

forces

(Doral

et

al.,

2010).

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A pathological Achilles tendon, regardless if damaged by mechanical forces, genetic factors, impaired development, or even aging, is significantly different from the healthy tendon on

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histologic examination (Neugebauer and Hawkins, 2012; Plate et al., 2013; Wang et al., 2006). Regardless of the pathology, disorders of the tendon occur both within cells and the extracellular

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matrix (Chamberlain et al., 2013). In tendinosis, one may see the disruption and disorientation of

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collagen organization, separation of fibers, and a simultaneous increase in the content of basic synovial substances. The cells and vascular spaces become more apparent, and there may be

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vascularization, necrosis, or calcification within the tendon (Khan et al., 1999). Partial rupture of the Achilles tendon is associated with inflammation. Histologically, it is

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characterized by a high content of fibroblasts and myofibroblasts, degenerative changes, and the presence of typical inflammatory cells (Khan et al., 1999). Tendinopathies of the AT occur as a result of failed tendon regeneration. The process of self-healing within the pathological tendon occurs chaotically and is accompanied by random proliferation of damaged tenocytes. Following

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a tear, the amount of collagen fibers and other ECM proteins is increased (Pingel et al., 2014; van Dijk et al., 2011). Additionally, there is increased production of type III collagen to maintain sufficient amounts for repair (Pingel et al., 2014). The pathological changes that occur in these diseases cause instability in the structure of the Achilles tendon and disturb its mechanical properties. This increases the risk of additional damage (Maffulli et al., 1998). The usage of light

microscopy, along with histological and immunohistochemical methods, may be considered as a good diagnostic tool for diseases of the Achilles tendon. Comprehensive knowledge on many of the histological components of the AT is available and additionally offers insight on factors that may contribute to potential tendinopathy. A complex understanding of the interplay of these factors in healthy tissue as compared with pathologic tissue could provide further clues to potential therapies. Although there is a wide range of components

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in the Achilles tendon’s structure, more studies on genetic associations are needed to determine

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variations within the framework of the tendon. For example, recent studies have reported genetic polymorphisms leading to varying expression levels of matrix metalloproteinase-3 (MMP3) and

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tissue inhibitor of metalloproteinase-2 (TIMP2) to be significantly associated with chronic

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Achilles tendinopathy risk (Nie et al., 2019). Another study found an association between vascular endothelial growth factor A (VEGF-A) isoforms and Achilles tendinopathy risk, thought to be

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related to angiogenesis signaling and extracellular matrix remodeling (Rahim et al., 2016). Many of the previously mentioned histologic components of the tendon may be affected by genetic

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polymorphisms that may stratify population groups having increased risk of developing tendinopathy, and bring such awareness into light. Studies at a more molecular level continue to elucidate the precise elements leading to tendinopathy and its related developmental elements. One such study elaborated on the distribution

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of protease-activated receptors (PARs) within the AT, finding them within the tendon tissue, the paratendinous tissue and in nerves and vasculature. Such activated PARs are associated with hyperalgesia and neovascularization, which may contribute to clinical symptoms of tendinopathy and could potentially be a therapeutic target in the future, although future studies must first compare their relative distributions in healthy and pathologic AT tissue (Christensen et al., 2015).

4. Biomechanics The Achilles tendon is the strongest, largest, and thickest tendon in the human body (Freedman et al., 2014; Joseph et al., 2012; Ying et al., 2003). It has a length of about 150 mm, a thickness of 5-7 mm, and a width of approximately 20 mm (Nickisch, 2009; O’Brien, 2009). The

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AT transmits forces generated by the strongest ankle plantar flexors (Dawe and Davis, 2011). It also crosses and acts on the knee, ankle, and subtalar joint. In this way, it provides optimal motion

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and stability (Joseph et al., 2012). The tendon can stretch up to 4% before incurring damage (O’Brien, 2005). It has been reported that the AT has a twisted structure: when viewed from the

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proximal to distal end, this twist was clockwise in the left leg and counterclockwise in the right

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leg (Edama et al., 2015; Szaro et al., 2009; van Gils et al., 1996). The elastic properties of the ATs change as one ages, including a decrease in thickness and an increase in stiffness (Narici and

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Maganaris, 2006; O’Brien et al., 2010). Young people have lower stiffness (Young’s modulus) and a higher tensile rupture stress (Narici et al., 2008; Thermann et al., 1995). Studies have shown

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that immobilization and a lack of physical activity have negative effects on tendon properties (Kvist et al., 1988; Narici and Maganaris, 2006). This is likely due to changes in cross sectional area (CSA) and Young’s modulus (Kasashima et al., 2002; Reeves et al., 2003). The average CSA of the AT is greater in runners than in non-runners, but no differences in stiffness were noted

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(Rosager et al., 2002). Additionally, as compared to women, it has been reported that ATs of men are stiffer, have a bigger CSA, and possess a higher maximum rupture force (Kubo et al., 2003; Maffulli et al., 2010; Thermann et al., 1995). During walking, the Achilles tendon yields loads of 2.6 kN (Komi, 1990), hopping yields 3.8 kN (Finni et al., 2000; Fukashiro et al., 1995), 2.2 kN during squat jumping, and a yield of 1.9

kN during countermovement jumping (Fukashiro et al., 1995). During running, the AT experiences loads greater than 9 kN, over 12 times the body weight (Byers and Berquist, 1996; Giddings et al., 2000; Komi, 1990). The mechanical properties of the AT have been based mainly on early in vitro studies (Blevins et al., 1994; Wren et al., 2001). The method of stretching isolated Achilles tendons provided a force-elongation curve, identifying four distinct regions: a toe region, linear region, a region of partial failure, and of total failure. A second useful method which measured intrinsic

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material properties of the AT was the stress-strain curve, obtaining the Young’s modulus (GPa,

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range: 1-2), the ultimate tendon stress – (tensile stress at failure: 100 MPa), and the ultimate tendon strain (strain at failure, range: 4-10%) (Maganaris et al., 2008; Stokes et al., 2010). Due to the

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usage of in vitro methods (factoring specimen differences, sterilization, and preservation methods)

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the relation of the stress-strain curve to AT pathology remains unclear (Smith et al., 1996; Stokes et al., 2010).

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The second approach, based on real-time examination, is in vivo methodology. The function of the AT has been measured by high resolution ultrasonography (Kongsgaard et al.,

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2011; Ying et al., 2003), 3D ultrasonography (Steven J Obst et al., 2014), panoramic ultrasound (Stokes et al., 2010), MRI (Kinugasa et al., 2010; Shin et al., 2008), dynamometry (Kubo et al., 2000; Maganaris and Paul, 1999; Reeves et al., 2003) and transient shear wave elastography (Aubry et al., 2013). The most crucial advantage of in vivo methods is the ability to assess the

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mechanical behavior of the AT during various activities (Arampatzis et al., 2005; Kubo et al., 2004, 2000; Maganaris and Paul, 2002; Muramatsu et al., 2001). During running, the AT may carry up to 110 MPa, more than the average ultimate tensile tendon stress of 100 MPa (Komi et al., 1992). This may be an explanation as to why the AT can sometimes rupture in a single movement (Maganaris et al., 2008). The Achilles tendon has demonstrated effective elasticity and

is able to recover around 16% of input energy while jumping on one foot and approximately 6% while walking (Lichtwark, 2005). Methodological differences, including the calculations of force or location of an ultrasonographic device, may lead to variable results in regard to biomechanics. For example, in young sedentary adults, ultimate tendon stress was found to range between 20-42 MPa, ultimate

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tendon strain was established between 5-8%, maximal tendon forces were calculated in a range of 200-3800 N, and elongation values were measured between 2-24 mm. Young's modulus was

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elaborated as ranging between 0.3-1.4 GPa and AT stiffness between 17-760 N/mm (Arampatzis et al., 2005; Kubo et al., 2004; Maganaris et al., 2008; Maganaris and Paul, 2002; Magnusson et

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al., 2001; Muramatsu et al., 2001). In vivo testing can be used in longitudinal investigations to

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study properties of the AT under various conditions such as aging, training methods, tendinopathies, and immobilization (Arya and Kulig, 2010; Barber et al., 2012; Grigg et al., 2012;

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Narici et al., 2008; Obst et al., 2013; Ohberg et al., 2004; Zhao et al., 2009). Studies with more accurate biomechanical systems are needed, especially with fresh AT samples, to establish

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definitive precision of biomechanical reference values for the tendon. New developments in MR and ultrasonography may help in future studies of the aforementioned biomechanical parameters and how various factors may affect them. Such in vivo testing may help to further understand not only the potential risk factors and mechanisms behind pathology, but also establish advances in

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the treatment of Achilles tendon pathology. Because of the high peak loads during various activities, the AT is the most frequently

ruptured tendon. The estimated injury rate is 12 in 100 000 individuals (Aubry et al., 2013). Approximately 59% of all AT tendinopathies are sports-related and this count has increased over the last 20-30 years (Bennett et al., 1986; Jarvinen et al., 2005; Maffulli et al., 1998; Stokes et al.,

2010). It is estimated that 75% of AT ruptures affecting middle aged men (between 30-49 years of age) were sports related (Jarvinen et al., 2005; Raikin et al., 2013). Risk factors which can predispose to rupture of the AT include poor ankle flexibility and strength, training mistakes, and hard running surfaces (Gibbon et al., 2000). The most common area for AT rupture is 2-6 cm proximal to its insertion (Dawe and Davis, 2011; Fukashiro et al., 1995).

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Early rehabilitation protocols following AT repair are balanced against increased risks of complications. Their resulting changes of AT biomechanical parameters may be analyzed and

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compared with physiological ones at baseline to develop a further understanding of the recovery process, which could potentially guide refinement of such protocols or help in the development of

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new ones. A recent in-vitro study using swine-harvested ATs looked at the usage of synthetic

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polyester augmentation across a variety of repair techniques to compare differences in stability with non-augmented ATs. Although cyclic testing was without influence, augmentation with such

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polyester tapes increased the maximum force and stress as compared with non-augmented ATs. Such advances could potentially be beneficial in patients with existing degeneration of the tendon

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or in those with high risks of re-rupture, although further studies to elucidate feasibility and possible indications are needed (Jahnke et al., 2019). Biomechanical changes, such as foot strike patterns, have been implicated in modification of various parameters of the Achilles tendon including the rate of loading, exerted force, and

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potential for injury. Functional AT properties have been shown to vary across differing footfall patterns: a forefoot strike pattern had significantly higher peak ultrasound transmission velocity during walking and running as compared with a rearfoot strike pattern, suggesting a difference in specific elastic modulus of the ATs in these two groups. A greater instantaneous elastic modulus of the AT in forefoot strike patterns may be advantageous during activities needing rapid force

development and potentially protect against strain if they may be attributed to tendon adaptation; more studies are required to determine the precise etiology of these variations (Wearing et al., 2019).

5. Conclusion

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The Achilles tendon is among the most studied tendons of the human body, with significant details elucidated in respect to its anatomy, histology, and biomechanics. This knowledge plays a

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key role in understanding normal function as well as potential imbalances within pathological states. With continued prevalence of injury, a proper understanding of the tendon’s properties and

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its supporting anatomical structures may help surgeons gain a better understanding of physical

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examination findings and remain alert to crucial components of the tendon. Within existing biomechanical knowledge, studies should be undertaken in respect to possible mechanics that may

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reduce wear on the tendon and help understand the factors that lead to the development of AT pathology. Potential modifiers of the biomechanical properties (both preventive, such as foot-strike

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patterns, and therapeutic, such as artificial augmentation) should be studied to facilitate the development of new interventions and rehabilitation protocols for tendinopathy. On the basis of histological findings, further research should be attempted in respect to potential therapies of benefit at a more microscopic level, spanning from possible pathology-inducing receptors to

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potentiators of tendinopathy development. Genetic factors influencing such histologic components should also continue to be studied to determine potential predisposition to tendon pathology. Declarations of interest: none. We wish to confirm that there are no known conflicts of interest associated with this publication. Ethical statement None/Not applicable.

ACKNOWLEDGEMENTS Krzysztof A. Tomaszewski was supported by the Polish Ministry of Science and Higher Education grant for young scientists. Authors acknowledge the financial support provided by the National

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Science Center Poland (Opus program no. UMO-2014/13/B/ST7/00690).

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Dr. Przemysław A. Pękala was supported by the Foundation for Polish Science.

References Abate, M., Oliva, F., Schiavone, C., Salini, V., 2012. Achilles tendinopathy in amateur runners: role of adiposity (Tendinopathies and obesity). Muscles. Ligaments Tendons J. 2, 44–8. https://doi.org/10.13838/j.cnki.kjgc.2014.02.041 Adams, J.C., 2001. Thrombospondins: multifunctional regulators of cell interactions. Annu. Rev.

of

Cell Dev. Biol. 17, 25–51. https://doi.org/10.1146/annurev.cellbio.17.1.25 Adams, J.C., Lawler, J., 2011. The thrombospondins. Cold Spring Harb. Perspect. Biol. 3, 1–29.

ro

https://doi.org/10.1101/cshperspect.a009712

Almonroeder, T., Willson, J.D., Kernozek, T.W., 2013. The effect of foot strike pattern on achilles load

during

running.

Ann.

Eng.

41,

1758–1766.

re

https://doi.org/10.1007/s10439-013-0819-1

Biomed.

-p

tendon

Apaydin, N., Bozkurt, M., Loukas, M., Vefali, H., Tubbs, R.S., Esmer, A.F., 2009. Relationships

lP

of the sural nerve with the calcaneal tendon: an anatomical study with surgical and clinical implications. Surg. Radiol. Anat. 31, 775–780. https://doi.org/10.1007/s00276-009-0520-0

ur na

Appy-Fedida, B., Vernois, J., Krief, E., Gouron, R., Mertl, P., Havet, E., 2015. Risk of sural nerve injury during lateral distal Achilles tendinoscopy: a cadaver study. Orthop. Traumatol. Surg. Res. 101, 93–96. https://doi.org/10.1016/j.otsr.2014.10.019 Arampatzis, A., Stafilidis, S., DeMonte, G., Karamanidis, K., Morey-Klapsing, G., Bruggemann,

Jo

G.P., 2005. Strain and elongation of the human gastrocnemius tendon and aponeurosis during maximal

plantarflexion

effort.

J.

Biomech.

38,

833–841.

https://doi.org/10.1016/j.jbiomech.2004.04.031

Arya, S., Kulig, K., 2010. Tendinopathy alters mechanical and material properties of the Achilles tendon. J. Appl. Physiol. 108, 670–675. https://doi.org/10.1152/japplphysiol.00259.2009

Åström, M., 2000. Laser Doppler flowmetry in the assessment of tendon blood flow. Scand. J. Med. Sci. Sport. 10, 365–367. https://doi.org/10.1034/j.1600-0838.2000.010006365.x Aubry, S., Risson, J.-R., Kastler, A., Barbier-Brion, B., Siliman, G., Runge, M., Kastler, B., 2013. Biomechanical properties of the calcaneal tendon in vivo assessed by transient shear wave elastography. Skeletal Radiol. 42, 1143–1150. https://doi.org/10.1007/s00256-013-1649-9

of

Barber, L., Barrett, R., Lichtwark, G., 2012. Medial gastrocnemius muscle fascicle active torquelength and Achilles tendon properties in young adults with spastic cerebral palsy. J. Biomech.

ro

45, 2526–2530. https://doi.org/10.1016/j.jbiomech.2012.07.018 Benjamin, M., Evans, E.J., 1990. Fibrocartilage. J. Anat. 171, 1–15.

tendons.

J.

Zool.

209,

537–548.

https://doi.org/10.1111/j.1469-

re

mammalian

-p

Bennett, M.B., Ker, R.F., Imery, N.J., Alexander, R.M.N., 1986. Mechanical properties of various

7998.1986.tb03609.x

lP

Bhattacharyya, M., Gerber, B., 2009. Mini-invasive surgical repair of the Achilles tendon-does it reduce post-operative morbidity? Int. Orthop. 33, 151–156. https://doi.org/10.1007/s00264-

ur na

008-0564-5

Bjur, D., Alfredson, H., Forsgren, S., 2005. The innervation pattern of the human Achilles tendon: studies of the normal and tendinosis tendon with markers for general and sensory innervation. Cell Tissue Res. 320, 201–206. https://doi.org/10.1007/s00441-004-1014-3

Jo

Blackmon, J.A., Atsas, S., Clarkson, M.J., Fox, J.N., Daney, B.T., Dodson, S.C., Lambert, H.W., 2013. Locating the sural nerve during calcaneal (Achilles) tendon repair with confidence: a cadaveric

study

with

clinical

applications.

J.

Foot

Ankle

Surg.

52,

42–47.

https://doi.org/10.1053/j.jfas.2012.09.010 Blevins, F.T., Hecker, A.T., Bigler, G.T., Boland, A.L., Hayes, W.C., 1994. The effects of donor

age and strain rate on the biomechanical properties of bone-patellar tendon-bone allografts. Am. J. Sports Med. 22, 328–333. https://doi.org/10.1177/036354659402200306 Byers, G.E. 3rd, Berquist, T.H., 1996. Radiology of sports-related injuries. Curr. Probl. Diagn. Radiol. 25, 1–49. Campanelli, V., Fantini, M., Faccioli, N., Cangemi, A., Pozzo, A., Sbarbati, A., 2011. Three-

219, 622–631. https://doi.org/10.1111/j.1469-7580.2011.01420.x

of

dimensional morphology of heel fat pad: an in vivo computed tomography study. J. Anat.

ro

Chamberlain, C.S., Duenwald-Kuehl, S.E., Okotie, G., Brounts, S.H., Baer, G.S., Vanderby, R., 2013. Temporal healing in rat achilles tendon: ultrasound correlations. Ann. Biomed. Eng.

-p

41, 477–487. https://doi.org/10.1007/s10439-012-0689-y

re

Chen, T.M., Rozen, W.M., Pan, W.-R., Ashton, M.W., Richardson, M.D., Taylor, G.I., 2009. The arterial anatomy of the Achilles tendon: anatomical study and clinical implications. Clin.

lP

Anat. 22, 377–385. https://doi.org/10.1002/ca.20758

Christensen, J., Alfredson, H., Andersson, G., 2015. Protease-Activated Receptors in the Achilles

ur na

Tendon–A Potential Explanation for the Excessive Pain Signalling in Tendinopathy. Mol. Pain 11. https://doi.org/10.1186/s12990-015-0007-4 Corps, A.N., Robinson, A.H.N., Movin, T., Costa, M.L., Hazleman, B.L., Riley, G.P., 2006. Increased expression of aggrecan and biglycan mRNA in Achilles tendinopathy.

Jo

Rheumatology (Oxford). 45, 291–294. https://doi.org/10.1093/rheumatology/kei152

Dawe, E.J.C., Davis, J., 2011. (vi) Anatomy and biomechanics of the foot and ankle. Orthop. Trauma 25, 279–286. https://doi.org/10.1016/j.mporth.2011.02.004

De Jonge, S., Van Den Berg, C., De Vos, R.J., Van Der Heide, H.J.L., Weir, A., Verhaar, J.A.N., Bierma-Zeinstra, S.M.A., Tol, J.L., 2011. Incidence of midportion Achilles tendinopathy in

the general population. Br. J. Sports Med. 45, 1026–1028. https://doi.org/10.1136/bjsports2011-090342 De Marchi, A., Pozza, S., Cenna, E., Cavallo, F., Gays, G., Simbula, L., De Petro, P., Massè, A., Massazza, G., 2018. In Achilles tendinopathy, the neovascularization, detected by contrastenhanced ultrasound (CEUS), is abundant but not related to symptoms. Knee Surgery, Sport.

of

Traumatol. Arthrosc. 26, 2051–2058. https://doi.org/10.1007/s00167-017-4710-8 De Palma, L., Marinelli, M., Memè, L., Pavan, M., 2004. Immunohistochemistry of the enthesis of

the

human

Achilles

tendon.

Foot

Ankle

Int.

25,

414–418.

ro

organ

https://doi.org/10.1177/107110070402500609

-p

Del Buono, A., Chan, O., Maffulli, N., 2013. Achilles tendon: functional anatomy and novel

re

emerging models of imaging classification. Int. Orthop. https://doi.org/10.1007/s00264-0121743-y

lP

Doral, M.N., Alam, M., Bozkurt, M., Turhan, E., Atay, O.A., Donmez, G., Maffulli, N., 2010. Functional anatomy of the Achilles tendon. Knee Surg. Sports Traumatol. Arthrosc. 18, 638–

ur na

643. https://doi.org/10.1007/s00167-010-1083-7 Edama, M., Kubo, M., Onishi, H., Takabayashi, T., Inai, T., Yokoyama, E., Hiroshi, W., Satoshi, N., Kageyama, I., 2015. The twisted structure of the human Achilles tendon. Scand. J. Med. Sci. Sports 25, e497-503. https://doi.org/10.1111/sms.12342

Jo

Finni, T., Komi, P. V., Lepola, V., 2000. In vivo human triceps surae and quadriceps femoris muscle function in a squat jump and counter movement jump. Eur. J. Appl. Physiol. 83, 416– 426. https://doi.org/10.1007/s004210000289

Franchi, M., Fini, M., Quaranta, M., De Pasquale, V., Raspanti, M., Giavaresi, G., Ottani, V., Ruggeri, A., 2007. Crimp morphology in relaxed and stretched rat Achilles tendon. J. Anat.

210, 1–7. https://doi.org/10.1111/j.1469-7580.2006.00666.x Franz, J.R., Thelen, D.G., 2016. Imaging and simulation of Achilles tendon dynamics: Implications for walking performance in the elderly. J. Biomech. 49, 1403–1410. https://doi.org/10.1016/j.jbiomech.2016.04.032 Freedman, B.R., Gordon, J.A., Soslowsky, L.J., 2014. The Achilles tendon: fundamental

of

properties and mechanisms governing healing. Muscles. Ligaments Tendons J. 4, 245–255. Frolova, E.G., Drazba, J., Krukovets, I., Kostenko, V., Blech, L., Harry, C., Vasanji, A., Drumm,

ro

C., Sul, P., Jenniskens, G.J., Plow, E.F., Stenina-Adognravi, O., 2014. Control of organization

https://doi.org/10.1016/j.matbio.2014.02.003

-p

and function of muscle and tendon by thrombospondin-4. Matrix Biol. 37, 35–48.

re

Fukashiro, S., Komi, P. V, Jarvinen, M., Miyashita, M., 1995. In vivo Achilles tendon loading during jumping in humans. Eur. J. Appl. Physiol. Occup. Physiol. 71, 453–458.

lP

Fukuta, S., Oyama, M., Kavalkovich, K., Fu, F.H., Niyibizi, C., 1998. Identification of types II, IX and X collagens at the insertion site of the bovine achilles tendon. Matrix Biol. 17, 65–73.

ur na

Gibbon, W.W., Cooper, J.R., Radcliffe, G.S., 2000. Distribution of sonographically detected tendon abnormalities in patients with a clinical diagnosis of chronic Achilles tendinosis. J. Clin.

Ultrasound

28,

61–66.

https://doi.org/10.1002/(SICI)1097-

0096(200002)28:2<61::AID-JCU1>3.0.CO;2-R

Jo

Gibson, M.A., Cleary, E.G., 1987. The immunohistochemical localisation of microfibrilassociated glycoprotein (MAGP) in elastic and non-elastic tissues. Immunol. Cell Biol. 65 ( Pt 4), 345–356. https://doi.org/10.1038/icb.1987.39

Giddings, V.L., Beaupré, G.S., Whalen, R.T., Carter, D.R., 2000. Calcaneal loading during walking

and

running.

Med.

Sci.

Sports

Exerc.

32,

627–634.

https://doi.org/10.1097/00005768-200003000-00012 Gollnick, P.D., Sjödin, B., Karlsson, J., Jansson, E., Saltin, B., 1974. Human soleus muscle: A comparison of fiber composition and enzyme activities with other leg muscles. Pflügers Arch. Eur. J. Physiol. 348, 247–255. https://doi.org/10.1007/BF00587415 Grigg, N.L., Wearing, S.C., Smeathers, J.E., 2012. Achilles tendinopathy has an aberrant strain to

eccentric

exercise.

Med.

Sci.

Sports

Exerc.

44,

12–17.

of

response

https://doi.org/10.1249/MSS.0b013e318227fa8c

ro

Handsfield, G.G., Inouye, J.M., Slane, L.C., Thelen, D.G., Miller, G.W., Blemker, S.S., 2017. A 3D model of the Achilles tendon to determine the mechanisms underlying nonuniform tendon

-p

displacements. J. Biomech. 51, 17–25. https://doi.org/10.1016/j.jbiomech.2016.11.062

re

Hedbom, E., Heinegard, D., 1989. Interaction of a 59-kDa connective tissue matrix protein with collagen I and collagen II. J. Biol. Chem. 264, 6898–6905.

lP

Henninger, H.B., Underwood, C.J., Romney, S.J., Davis, G.L., Weiss, J.A., 2013. Effect of elastin digestion on the quasi-static tensile response of medial collateral ligament. J. Orthop. Res.

ur na

31, 1226–1233. https://doi.org/10.1002/jor.22352 Jahnke, A., Gernandt, M., Hudel, H., Ahmed, G.A., Rickert, M., Fonseca Ulloa, C.A., Stolz, D., 2019. Biomechanical testing of various suture techniques for Achilles tendon repair with and without augmentation by using synthetic polyester grafts. J. Biomech. 93, 132–139.

Jo

https://doi.org/10.1016/j.jbiomech.2019.06.021

Jarvinen, T.A.H., Kannus, P., Maffulli, N., Khan, K.M., 2005. Achilles tendon disorders: etiology and epidemiology. Foot Ankle Clin. 10, 255–266. https://doi.org/10.1016/j.fcl.2005.01.013

Jorgensen, U., 1985. Achillodynia and loss of heel pad shock absorbency. Am. J. Sports Med. 13, 128–132. https://doi.org/10.1177/036354658501300209

Joseph, M.F., Lillie, K.R., Bergeron, D.J., Denegar, C.R., 2012. Measuring Achilles tendon mechanical properties: a reliable, noninvasive method. J. strength Cond. Res. 26, 2017–2020. https://doi.org/10.1519/JSC.0b013e31825bb47f Jozsa, L., Lehto, M., Kannus, P., Kvist, M., Reffy, A., Vieno, T., Järvinen, M., Demel, S., Elek, E., 1989. Fibronectin and laminin in achilles tendon. Acta Orthop. 60, 469–471.

of

https://doi.org/10.3109/17453678909149322 Kammar, H., Carmont, M.R., Kots, E., Laver, L., Mann, G., Nyska, M., Mei-Dan, O., 2014.

ro

Anatomy of the sural nerve and its relation to the achilles tendon by ultrasound examination. Orthopedics 37, e298-301. https://doi.org/10.3928/01477447-20140225-64

-p

Kannus, P., 2000. Structure of the tendon connective tissue. Scand. J. Med. Sci. Sport. 10, 312–

re

320. https://doi.org/10.1034/j.1600-0838.2000.010006312.x

Kannus, P., Jozsa, L., Järvinen, T.A.H., Järvinen, T.L.N., Kvist, M., Natri, A., Järvinen, M., 1998.

lP

Location and distribution of non-collagenous matrix proteins in musculoskeletal tissues of rat. Histochem. J. 30, 799–810. https://doi.org/10.1023/A:1003448106673

ur na

Kasashima, Y., Smith, R.K.W., Birch, H.L., Takahashi, T., Kusano, K., Goodship, A.E., 2002. Exercise-induced tendon hypertrophy: cross-sectional area changes during growth are influenced by exercise. Equine Vet. J. Suppl. 264–268. https://doi.org/10.1111/j.20423306.2002.tb05430.x

Jo

Khan, K.M., Cook, J.L., Bonar, F., Harcourt, P., Åstrom, M., 1999. Histopathology of common tendinopathies: Update and implications for clinical management. Sport. Med. 27, 393–408. https://doi.org/10.2165/00007256-199927060-00004

Kielty, C.M., Whittaker, S.P., Grant, M.E., Shuttleworth, C.A., 1992. Type VI collagen microfibrils: evidence for a structural association with hyaluronan. J. Cell Biol. 118, 979–

990. Kinugasa, R., Hodgson, J.A., Edgerton, V.R., Shin, D.D., Sinha, S., 2010. Reduction in tendon elasticity from unloading is unrelated to its hypertrophy. J. Appl. Physiol. 109, 870–877. https://doi.org/10.1152/japplphysiol.00384.2010 Klenerman, L., 2007. The early history of tendo Achillis and its rupture. J. Bone Joint Surg. Br.

of

89–B, 545–547. https://doi.org/10.1302/0301-620x.89b4.18978 Knobloch, K., 2008. The role of tendon microcirculation in Achilles and patellar tendinopathy. J.

ro

Orthop. Surg. Res. 3. https://doi.org/10.1186/1749-799X-3-18

Komi, P. V., 1990. Relevance of in vivo force measurements to human biomechanics. J. Biomech.

-p

23, 23–34. https://doi.org/10.1016/0021-9290(90)90038-5

re

Komi, P. V, Fukashiro, S., Jarvinen, M., 1992. Biomechanical loading of Achilles tendon during normal locomotion. Clin. Sports Med. 11, 521–531.

lP

Kongsgaard, M., Nielsen, C.H., Hegnsvad, S., Aagaard, P., Magnusson, S.P., 2011. Mechanical properties of the human Achilles tendon, in vivo. Clin. Biomech. (Bristol, Avon) 26, 772–

ur na

777. https://doi.org/10.1016/j.clinbiomech.2011.02.011 Kristoffersen, M., Ohberg, L., Johnston, C., Alfredson, H., 2005. Neovascularisation in chronic tendon injuries detected with colour Doppler ultrasound in horse and man: implications for research and treatment. Knee Surg. Sports Traumatol. Arthrosc. 13, 505–508.

Jo

https://doi.org/10.1007/s00167-005-0648-3

Kubo, K., Akima, H., Ushiyama, J., Tabata, I., Fukuoka, H., Kanehisa, H., Fukunaga, T., 2004. Effects of resistance training during bed rest on the viscoelastic properties of tendon structures in the lower limb. Scand. J. Med. Sci. Sport. 14, 296–302. https://doi.org/10.1111/j.16000838.2003.00368.x

Kubo, K., Kanehisa, H., Miyatani, M., Tachi, M., Fukunaga, T., 2003. Effect of low-load resistance training on the tendon properties in middle-aged and elderly women. Acta Physiol. Scand. 178, 25–32. https://doi.org/10.1046/j.1365-201X.2003.01097.x Kubo, K., Kanehisa, H., Takeshita, D., Kawakami, Y., Fukashiro, S., Fukunaga, T., 2000. In vivo dynamics of human medial gastrocnemius muscle-tendon complex during stretch-shortening

of

cycle exercise. Acta Physiol. Scand. 170, 127–135. https://doi.org/10.1046/j.1365201x.2000.00768.x

ro

Kvist, M.H., Lehto, M.U., Jozsa, L., Jarvinen, M., Kvist, H.T., 1988. Chronic achilles paratenonitis. An immunohistologic study of fibronectin and fibrinogen. Am. J. Sports Med.

-p

16, 616–623. https://doi.org/10.1177/036354658801600611

re

LeBaron, R.G., Zimmermann, D.R., Ruoslahti, E., 1992. Hyaluronate binding properties of versican. J. Biol. Chem. 267, 10003–10010.

lP

Lichtwark, G.A., 2005. In vivo mechanical properties of the human Achilles tendon during onelegged hopping. J. Exp. Biol. 208, 4715–4725. https://doi.org/10.1242/jeb.01950

ur na

Lohrer, H., Arentz, S., Nauck, T., Dorn-Lange, N. V, Konerding, M.A., 2008. The Achilles Tendon Insertion is Crescent-shaped: An In Vitro Anatomic Investigation. Clin. Orthop. Relat. Res. https://doi.org/10.1007/s11999-008-0298-0 Longo, U.G., Ronga, M., Maffulli, N., 2009. Achilles tendinopathy. Sports Med. Arthrosc. 17,

Jo

112–126. https://doi.org/10.1097/JSA.0b013e3181a3d625

Maes, R., Copin, G., Averous, C., 2006. Is percutaneous repair of the Achilles tendon a safe technique? A study of 124 cases. Acta Orthop. Belg. 72, 179–183.

Maffulli, N., Khan, K.M., Puddu, G., 1998. Overuse tendon conditions: time to change a confusing terminology. Arthroscopy 14, 840–843.

Maffulli, N., Longo, U.G., Ronga, M., Khanna, A., Denaro, V., 2010. Favorable Outcome of Percutaneous Repair of Achilles Tendon Ruptures in the Elderly. Clin. Orthop. Relat. Res. https://doi.org/10.1007/s11999-009-0944-1 Maffulli, N., Via, A.G., Oliva, F., 2015. Chronic Achilles Tendon Disorders: Tendinopathy and Chronic Rupture. Clin. Sports Med. 34, 607–624. https://doi.org/10.1016/j.csm.2015.06.010

of

Maganaris, C.N., Narici, M. V, Maffulli, N., 2008. Biomechanics of the Achilles tendon. Disabil. Rehabil. 30, 1542–1547. https://doi.org/10.1080/09638280701785494

ro

Maganaris, C.N., Paul, J.P., 2002. Tensile properties of the in vivo human gastrocnemius tendon. J. Biomech. 35, 1639–1646. https://doi.org/10.1016/S0021-9290(02)00240-3

-p

Maganaris, C.N., Paul, J.P., 1999. In vivo human tendon mechanical properties. J. Physiol. 521,

re

307–313. https://doi.org/10.1111/j.1469-7793.1999.00307.x

Magnusson, S.P., Aagaard, P., Dyhre-Poulsen, P., Kjaer, M., 2001. Load-displacement properties

lP

of the human triceps surae aponeurosis in vivo. J. Physiol. 531, 277–288. Muramatsu, T., Muraoka, T., Takeshita, D., Kawakami, Y., Hirano, Y., Fukunaga, T., 2001.

ur na

Mechanical properties of tendon and aponeurosis of human gastrocnemius muscle in vivo. J. Appl. Physiol. 90, 1671–1678. https://doi.org/10.1152/jappl.2001.90.5.1671 Narici, M. V, Maffulli, N., Maganaris, C.N., 2008. Ageing of human muscles and tendons. Disabil. Rehabil. 30, 1548–1554. https://doi.org/10.1080/09638280701831058

Jo

Narici, M. V, Maganaris, C.N., 2006. Adaptability of elderly human muscles and tendons to increased loading. J. Anat. https://doi.org/10.1111/j.1469-7580.2006.00548.x

Neugebauer, J.M., Hawkins, D.A., 2012. Identifying factors related to Achilles tendon stress, strain, and stiffness before and after 6 months of growth in youth 10-14 years of age. J. Biomech. 45, 2457–2461. https://doi.org/10.1016/j.jbiomech.2012.06.027

Nickisch, F., 2009. Anatomy of the achilles tendon. Achilles Tendon Treat. Rehabil. 3–16. https://doi.org/10.1007/978-0-387-79205-7_1 Nie, G., Wen, X., Liang, X., Zhao, H., Li, Y., Lu, J., 2019. Additional evidence supports association of common genetic variants in MMP3 and TIMP2 with increased risk of chronic Achilles

tendinopathy

susceptibility.

J.

Sci.

Med.

Sport.

of

https://doi.org/10.1016/j.jsams.2019.05.021 Niyibizi, C., Sagarriga Visconti, C., Gibson, G., Kavalkovich, K., 1996. Identification and

ro

immunolocalization of type X collagen at the ligament-bone interface. Biochem. Biophys. Res. Commun. 222, 584–589. https://doi.org/10.1006/bbrc.1996.0787

-p

O’Brien, M., 2009. Anatomy of the achilles tendon. Achilles Tendon Treat. Rehabil. 3–16.

re

https://doi.org/10.1007/978-0-387-79205-7_1

O’Brien, M., 2005. The anatomy of the Achilles tendon. Foot Ankle Clin. 10, 225–238.

lP

https://doi.org/10.1016/j.fcl.2005.01.011

O’Brien, T.D., Reeves, N.D., Baltzopoulos, V., Jones, D.A., Maganaris, C.N., 2010. Mechanical

ur na

properties of the patellar tendon in adults and children. J. Biomech. 43, 1190–1195. https://doi.org/10.1016/j.jbiomech.2009.11.028 Obst, S.J., Barrett, R.S., Newsham-West, R., 2013. Immediate effect of exercise on achilles tendon properties:

systematic

review.

Med.

Sci.

Sports

Exerc.

45,

1534–1544.

Jo

https://doi.org/10.1249/MSS.0b013e318289d821

Obst, S.J., Newsham-West, R., Barrett, R.S., 2014. InVivo measurement of human achilles tendon morphology using freehand 3-D ultrasound. Ultrasound Med. Biol. 40, 62–70. https://doi.org/10.1016/j.ultrasmedbio.2013.08.009 Obst, S.J., Newsham-West, R., Barrett, R.S., 2014. In vivo measurement of human achilles tendon

morphology using freehand 3-D ultrasound. Ultrasound Med. Biol. 40, 62–70. https://doi.org/10.1016/j.ultrasmedbio.2013.08.009 Öhberg, L., Lorentzon, R., Alfredson, H., 2004. Eccentric training in patients with chronic Achilles tendinosis: Normalised tendon structure and decreased thickness at follow up. Br. J. Sports Med. 38, 8–11. https://doi.org/10.1136/bjsm.2001.000284

of

Pajala, A., Melkko, J., Leppilahti, J., Ohtonen, P., Soini, Y., Risteli, J., 2009. Tenascin-C and type I and III collagen expression in total Achilles tendon rupture. An immunohistochemical study.

ro

Histol. Histopathol. 24, 1207–1211. https://doi.org/10.14670/HH-24.1207

293. https://doi.org/10.1007/s12178-013-9185-8

-p

Pedowitz, D., Kirwan, G., 2013. Achilles tendon ruptures. Curr. Rev. Musculoskelet. Med. 6, 285–

re

Pekala, P.A., Henry, B.M., Ochala, A., Kopacz, P., Taton, G., Mlyniec, A., Walocha, J.A., Tomaszewski, K.A., 2017. The twisted structure of the Achilles tendon unraveled: A detailed

lP

quantitative and qualitative anatomical investigation. Scand. J. Med. Sci. Sports 27, 1705– 1715. https://doi.org/10.1111/sms.12835

ur na

Perides, G., Rahemtulla, F., Lane, W.S., Asher, R.A., Bignami, A., 1992. Isolation of a large aggregating proteoglycan from human brain. J. Biol. Chem. 267, 23883–23887. Pichler, W., Tesch, N.P., Grechenig, W., Leithgoeb, O., Windisch, G., 2007. Anatomic variations of the musculotendinous junction of the soleus muscle and its clinical implications. Clin.

Jo

Anat. 20, 444–447. https://doi.org/10.1002/ca.20421

Pingel, J., Lu, Y., Starborg, T., Fredberg, U., Langberg, H., Nedergaard, A., Weis, M., Eyre, D., Kjaer, M., Kadler, K.E., 2014. 3-D ultrastructure and collagen composition of healthy and overloaded human tendon: evidence of tenocyte and matrix buckling. J. Anat. 224, 548–555. https://doi.org/10.1111/joa.12164

Plate, J.F., Wiggins, W.F., Haubruck, P., Scott, A.T., Smith, T.L., Saul, K.R., Mannava, S., 2013. Normal aging alters in vivo passive biomechanical response of the rat gastrocnemius-Achilles muscle-tendon

unit.

J.

Biomech.

46,

450–455.

https://doi.org/10.1016/j.jbiomech.2012.11.007 Rahim, M., El Khoury, L.Y., Raleigh, S.M., Ribbans, W.J., Posthumus, M., Collins, M.,

of

September, A. V., 2016. Human Genetic Variation, Sport and Exercise Medicine, and Achilles Tendinopathy: Role for Angiogenesis-Associated Genes. Omi. A J. Integr. Biol. 20,

ro

520–527. https://doi.org/10.1089/omi.2016.0116

Raikin, S.M., Garras, D.N., Krapchev, P. V, 2013. Achilles tendon injuries in a United States

-p

population. Foot ankle Int. 34, 475–480. https://doi.org/10.1177/1071100713477621

re

Rebeccato, A., Santini, S., Salmaso, G., Nogarin, L., 2001. Repair of the achilles tendon rupture: A functional comparison of three surgical techniques. J. Foot Ankle Surg. 40, 188–194.

lP

https://doi.org/10.1016/S1067-2516(01)80018-1

Reeves, N.D., Maganaris, C.N., Narici, M. V, 2003. Effect of strength training on human patella

ur na

tendon mechanical properties of older individuals. J. Physiol. 548, 971–981. https://doi.org/10.1113/jphysiol.2002.035576 Reiter, M., Ulreich, N., Dirisamer, A., Tscholakoff, D., Bucek, R.A., 2004. Colour and power Doppler sonography in symptomatic Achilles tendon disease. Int. J. Sports Med. 25, 301–

Jo

305. https://doi.org/10.1055/s-2004-815828

Rigozzi, S., Muller, R., Snedeker, J.G., 2009. Local strain measurement reveals a varied regional dependence of tensile tendon mechanics on glycosaminoglycan content. J. Biomech. 42, 1547–1552. https://doi.org/10.1016/j.jbiomech.2009.03.031 Rigozzi, S., Muller, R., Stemmer, A., Snedeker, J.G., 2013. Tendon glycosaminoglycan

proteoglycan sidechains promote collagen fibril sliding-AFM observations at the nanoscale. J. Biomech. 46, 813–818. https://doi.org/10.1016/j.jbiomech.2012.11.017 Rosager, S., Aagaard, P., Dyhre-Poulsen, P., Neergaard, K., Kjaer, M., Magnusson, S.P., 2002. Load-displacement properties of the human triceps surae aponeurosis and tendon in runners and non-runners. Scand. J. Med. Sci. Sport. 12, 90–98. https://doi.org/10.1034/j.1600-

of

0838.2002.120205.x Shin, D., Finni, T., Ahn, S., Hodgson, J.A., Lee, H.D., Edgerton, V.R., Sinha, S., 2008. In vivo

ro

estimation and repeatability of force-length relationship and stiffness of the human achilles tendon using phase contrast MRI. J. Magn. Reson. Imaging 28, 1039–1045.

-p

https://doi.org/10.1002/jmri.21533

re

Smith, C.W., Young, I.S., Kearney, J.N., 1996. Mechanical properties of tendons: changes with sterilization and preservation. J. Biomech. Eng. 118, 56–61.

lP

Spang, C., Alfredson, H., Ferguson, M., Roos, B., Bagge, J., Forsgren, S., 2013. The plantaris tendon in association with mid-portion Achilles tendinosis: tendinosis-like morphological

ur na

features and presence of a non-neuronal cholinergic system. Histol. Histopathol. 28, 623– 632. https://doi.org/10.14670/HH-28.623 Stokes, O.M., Theobald, P.S., Pugh, N.D., Nokes, L.D.M., 2010. Panoramic ultrasound to measure in

vivo

tendo

Achilles

strain.

Foot

ankle

Int.

31,

905–909.

Jo

https://doi.org/10.3113/FAI.2010.0905

Suchak, A.A., Bostick, G., Reid, D., Blitz, S., Jomha, N., 2005. The incidence of Achilles tendon ruptures

in

Edmonton,

Canada.

Foot

Ankle

Int.

26,

932–936.

https://doi.org/10.1177/107110070502601106 Szaro, P., Witkowski, G., Smigielski, R., Krajewski, P., Ciszek, B., 2009. Fascicles of the adult

human

Achilles

tendon

-

an

anatomical

study.

Ann.

Anat.

191,

586–593.

https://doi.org/10.1016/j.aanat.2009.07.006 Taylor, S.H., Al-Youha, S., Van Agtmael, T., Lu, Y., Wong, J., McGrouther, D.A., Kadler, K.E., 2011. Tendon is covered by a basement membrane epithelium that is required for cell retention

and

the

prevention

of

adhesion

formation.

PLoS

One

6,

e16337.

of

https://doi.org/10.1371/journal.pone.0016337 Thermann, H., Frerichs, O., Blewener, A., Krettek, C., Schandelmaier, P., 1995. Biomechanical of

human

achilles

tendon

rupture.

Unfallchirurg

98,

570–575.

ro

analyses

https://doi.org/10.1002/stem.113

ultrastructure.

Muscles.

Ligaments

Tendons

J.

3,

2–6.

re

Tendon’s

-p

Tresoldi, I., Oliva, F., Benvenuto, M., Fantini, M., Masuelli, L., Bei, R., Modesti, A., 2013.

https://doi.org/10.11138/mltj/2013.3.1.002

lP

van Dijk, C.N., van Sterkenburg, M.N., Wiegerinck, J.I., Karlsson, J., Maffulli, N., 2011. Terminology for Achilles tendon related disorders. Knee Surg. Sports Traumatol. Arthrosc.

ur na

19, 835–41. https://doi.org/10.1007/s00167-010-1374-z van Gils, C.C., Steed, R.H., Page, J.C., 1996. Torsion of the human Achilles tendon. J. Foot Ankle Surg. 35, 41–48.

Waggett, A.D., Ralphs, J.R., Kwan, A.P., Woodnutt, D., Benjamin, M., 1998. Characterization of

Jo

collagens and proteoglycans at the insertion of the human Achilles tendon. Matrix Biol. 16, 457–470.

Wang, V.M., Banack, T.M., Tsai, C.W., Flatow, E.L., Jepsen, K.J., 2006. Variability in tendon and knee joint biomechanics among inbred mouse strains. J. Orthop. Res. 24, 1200–1207. https://doi.org/10.1002/jor.20167

Wearing, S.C., Davis, I.S., Brauner, T., Hooper, S.L., Horstmann, T., 2019. Do habitual foot-strike patterns in running influence functional Achilles tendon properties during gait? J. Sports Sci. 1–9. https://doi.org/10.1080/02640414.2019.1663656 Wolff, K.S., Wibmer, A.G., Binder, H., Grissmann, T., Heinrich, K., Schauer, S., Nepp, R., Rois, S., Ritschl, H., Teufelsbauer, H., Pretterklieber, M.L., 2012. The avascular plane of the

new

treatment

option

after

rupture.

Eur.

J.

of

Achilles tendon: a quantitative anatomic and angiographic approach and a base for a possible Radiol.

1211–1215.

ro

https://doi.org/10.1016/j.ejrad.2011.03.015

81,

Wren, T.A., Yerby, S.A., Beaupre, G.S., Carter, D.R., 2001. Mechanical properties of the human

-p

achilles tendon. Clin. Biomech. (Bristol, Avon) 16, 245–251.

re

Yepes, H., Tang, M., Geddes, C., Glazebrook, M., Morris, S.F., Stanish, W.D., 2010. Digital vascular mapping of the integument about the Achilles tendon. J. Bone Joint Surg. Am. 92,

lP

1215–1220. https://doi.org/10.2106/JBJS.I.00743

Ying, M., Yeung, E., Li, B., Li, W., Lui, M., Tsoi, C.W., 2003. Sonographic evaluation of the size

ur na

of Achilles tendon: The effect of exercise and dominance of the ankle. Ultrasound Med. Biol. 29, 637–642. https://doi.org/10.1016/S0301-5629(03)00008-5 Zanetti, M., Metzdorf, A., Kundert, H.-P., Zollinger, H., Vienne, P., Seifert, B., Hodler, J., 2003. Achilles tendons: clinical relevance of neovascularization diagnosed with power Doppler US.

Jo

Radiology 227, 556–560. https://doi.org/10.1148/radiol.2272012069

Zantop, T., Tillmann, B., Petersen, W., 2003. Quantitative assessment of blood vessels of the human Achilles tendon: an immunohistochemical cadaver study. Arch. Orthop. Trauma Surg. 123, 501–504. https://doi.org/10.1007/s00402-003-0491-2 Zappia, M., Berritto, D., Oliva, F., Maffulli, N., 2018. High resolution real time ultrasonography

of the sural nerve after percutaneous repair of the Achilles tendon. Foot Ankle Surg. 24, 342– 346. https://doi.org/10.1016/j.fas.2017.03.006 Zhao, H., Ren, Y., Wu, Y.-N., Liu, S.Q., Zhang, L.-Q., 2009. Ultrasonic evaluations of Achilles tendon

mechanical

properties

poststroke.

J.

Appl.

Physiol.

106,

843–849.

Jo

ur na

lP

re

-p

ro

of

https://doi.org/10.1152/japplphysiol.91212.2008

Figures

of

Figure 1. The Achilles tendon as a whole and the plantaris muscle tendon seen from the posterior

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surface.

Figure 2. Torsion of the Achilles tendon subtendons (originating from the lateral and medial heads

Jo

of the gastrocnemius muscle and the soleus muscle).

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Figure 3. Schematic of the blood supply to the Achilles tendon from above. The point of insertion,

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at 1 cm, receives its supply via the posterior vessels from the medial artery (posterior tibial artery). At 4 cm, the midsection is vascularized poorly by anterior vessels from the lateral artery (peroneal

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artery). The proximal section, between 7-10 cm, receives its blood supply from large anterior vessels from the medial artery (posterior tibial artery). At 13 cm, the aponeurosis is vascularized by large anterior vessels from the medial artery (posterior tibial artery) (redrawn from Chen et al.

Jo

2009).

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Figure 4. Schematic of the Achilles tendon blood supply. A: Blood supply pattern elaborated by

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Chen et al. in 2009 depicting vascularization of the wedge-shaped midsection by the peroneal

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artery, with the remaining proximal and distal sections supplied by the posterior tibial artery. B: Previously reported blood supply patterns of the Achilles tendon showing equal contributions from

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the peroneal and posterior tibial artery (redrawn from Chen et al. 2009).