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Physiopathology of the repair process of lesions of Achilles tendon
Foot and Ankle Surgery 12 (2006) 5–11 www.elsevier.com/locate/fas
Physiopathology of the repair process of lesions of Achilles tendon L. de Palma*, A. Gigante, S. Rapali Clinica Ortopedica, Universita` Politecnica delle Marche—Ancona, Ospedali Riuniti Umberto 18-Lancisi-Salesi, Via Conca, 60100 Ancona, Italy Received 15 August 2005; accepted 30 August 2005
Achilles tendinopathy is related to the inflammationdegeneration of the Achilles-calcaneal-plantar system, whose function can be impaired due to a large number of causes. The functional unity of the Achilles-calcaneal-plantar system was demonstrated by Arandes and Viladot as early as 1953 [1]. This system is made up of the triceps surae with the Achilles tendon, the posterior trabecular system of the calcaneal tuberosity and the plantar aponeurosis (Fig. 1), and of some muscles that originate from the calcaneal tuberosity, signally flexor digiti minimi brevis and abductor hallucis medially, flexor digitorum brevis centrally, and abductor digiti minimi laterally [2]. Several factors have been invoked to explain Achilles tendinopathy, including degenerative changes, mechanical factors, iatrogenic causes (e.g. use of corticosteroids and fluoroquinolones), systemic disease (hypercholesterolemia, rheumatoid arthritis, SLE), and hyperthermia. The degeneration hypothesis centres on primitive regressive changes that would progressively weaken the tendon, leading to reduced mechanical resistance and ultimately to spontaneous rupture in normal functional conditions. This hypothesis is supported by degenerative changes found in ruptured Achilles tendons at histology [3, 4]. In addition, studies of autopsy samples and of experimental animals have shown that indirect trauma is unable to induce a subcutaneous lesion of healthy Achilles tendon. Overall, such investigations lend support to the hypothesis that a healthy tendon is unlikely to rupture however intense the functional stress to which it is subjected. According to the mechanical theory, the primitive degenerative changes are insufficient to account for all the * Corresponding author. Tel.: C39 71 5963349; fax: C39 71 5963349. E-mail address: [email protected] (L. de Palma).
causes of tendon rupture, while microtrauma is central to ruptures experienced by young subjects both in the presence and absence of other predisposing factors. The latter are numerous and include: inadequate training footwear [5], muscle fatigue induced by inappropriate training [6,7], and foot biomechanical changes related to particular anatomical conditions. According to Clement and co-workers [6], in the case of muscle fatigue the eccentric action of the gastrocnemius and soleus muscles subjects the tendon to extreme stress that may induce microtears. In addition, non-uniform stress forces applied on different zones of the tendon would favour ischaemic torque phenomena that in turn result in tendon vascular injury [6]. It has also been suggested [8] that a healthy tendon can rupture following forcible muscular exertion solely in the presence of particular anatomical conditions, such as a difference in thickness between muscle and tendon or the absence/insufficiency of the plantar muscle, which has the function to reduce and uniformly distribute the load on the Achilles tendon. Experimental investigations by Barfred and colleagues [9] have demonstrated that if linear traction is applied parallel to the muscle-tendon-bone system, the risk of rupture will involve the whole system uniformly, whereas oblique traction will be more likely to affect the tendon tissue. Such situations can obtain in sports requiring sprinting movements and in some conditions involving biomechanical imbalances of Achilles tendon secondary to particular anatomical conditions of the foot (e.g. pronation syndrome). The observation that 56% of athletes with Achilles tendinopathy overpronate the foot as they walk seems to lend support to this view [6]. These data lead to ascribe a large role to microtrauma in causing the rupture of the Achilles tendon in the absence of primitive degenerative changes. According to this theory, therefore, rupture may
1268-7731/$ - see front matter q 2005 European Foot and Ankle Society. Published by Elsevier Ireland Ltd. All rights reserved. doi:10.1016/j.fas.2005.08.005
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L. de Palma et al. / Foot and Ankle Surgery 12 (2006) 5–11
Fig. 1. The functional unity of the Achilles-calcaneal-plantar system is made up of the triceps surae with the Achilles tendon, the posterior trabecular system of the calcaneal tuberosity and the plantar aponeurosis.
result from multiple fibril tears due to microtrauma impairing the tendon’s mechanical resistance. Systemic disease (e.g. rheumatoid arthritis, SLE, gout) has been implicated in the pathogenesis of Achilles tendon lesions. However, degenerative changes related to the underlying disease have rarely been observed [10]. For instance, ruptures caused directly by rheumatoid disease are very rare [11], the few existing reports being attributable to the action of proteolytic enzymes released by rheumatoid synovitis of Achilles bursa, to a primitive rheumatoid enthesitis, and to rheumatoid vasculitis with chronic tendon hypoxia. More frequently, the lesion is related to high-dose topical or systemic cortisone administered to treat the disease. An influence of some drugs on degenerative tendon modifications has also been known for some time. Local cortisone causes necrotic changes in tendon tissue [12]. Moreover, reduction of painful symptoms due to the analgesic and anti-inflammatory action of corticosteroids induces patients to subject the tendon to increased functional stress, adding to the degenerative changes and ultimately leading to rupture [13]. Degenerative changes have also been attributed to fluoroquinolones antibiotics [14]. The hyperthermia that develops in the tendon after intense exercise is considered by some researchers as a further cause of tendon degeneration [15]. Wilson and Goodship [15] measured temperatures up to 45 8C following exertion, and Arancia et al. [16] demonstrated fibroblast damage already at 42 8C.
from tendon to bone tissue: (1) tendon; (2) non-calcified fibrocartilage; (3) calcified fibrocartilage; and (4) bone. Zones 2 and 3 are separated by a tidemark (Fig. 2). Achilles insertion tendinopathy is characterized histologically by hyaline degeneration foci evolving to disruption of the tendon tissue and necrosis [19] (Fig. 3). Further typical findings are microtears of the tendon tissue, calcification foci among the tendon fibres, tidemark disruption, thickening of the fibrocartilage layer with presence of hypertrophic chondrocytes and presence of degenerative microcystic cavities containing necrotic material [19]. The pathological involvement of Achilles tendon may exhibit inflammatory (peritendinitis) (Fig. 4), regressive (tendinosis) or, more frequently, mixed features (peritendinitis and tendinosis) [20]. Given the absence of a synovial sheath, tenosynovitic processes are not encountered. Peritendinitis may present in an acute or a chronic form. In the former, the peritenon is affected by an inflammatory process characterized by oedema, hyperemia and formation of a fibrin exudate (Fig. 4). The capillaries appear dilated (Fig. 4) and thrombotic phenomena are observed in smaller vessels. In chronic peritendinitis, increased fibroblast
1. Histological changes The histological changes induced by Achilles tendinopathy can affect the tendon body and/or the bone-tendon calcaneal insertion [17,18]. Achilles insertion tendinopathy is characterized by the inflammatory-degenerative involvement of the bone-tendon junction at the level of calcaneal insertion. In this tendon, the junction is of the direct type, entailing the presence of four distinct zones that can be recognized in the transition
Fig. 2. Achille’s bone-tendon junction. Four distinct zones can be recognized in the transition from tendon to bone tissue: tendon; noncalcified fibrocartilage; calcified fibrocartilage and bone. (Gomori’s stain, 100!).
L. de Palma et al. / Foot and Ankle Surgery 12 (2006) 5–11
Fig. 3. Biopsy from achilles tendinopathy which is characterized by the absence of cells and the presence of hyaline degeneration foci and necrosis. (Safranin O, 200!).
proliferation and adhesion processes are the prevalent findings at pathology [20]. In both acute and chronic forms, the inflammatory process affects the peritenon, largely sparing the tendon tissue. Tendinosis is a degenerative process of the tendon tissue, which may exhibit different anatomo-patologiche changes depending on the nature of regression phenomena. Typical features are changes in the matrix structure with modification of histochemical characteristics and an increased amorphous component. The collagen fibres present signs of degeneration and inhomogeneous fibre thickness. Tenocytes are fewer in number and altered in shape, with loss of the distinctive row arrangement. Vessels are arranged irregularly in the tendon tissue. Different histopathological features are observed in accordance with the characteristics of the degenerative process: hyaline (Fig. 3), mucoid, fibrinoid or fatty degeneration (Fig. 5), areas of calcification and areas of cartilage (Fig. 6) or bone metaplasia (Fig. 7). Matrix regression phenomena eventually impair the tendon’s biomechanical properties, ultimately leading to subcutaneous rupture. In subcutaneous lesions, histological features at the site of rupture change according to time of the examination and lesion severity. In complete rupture, the site of the rupture commonly lies 2–6 cm from the bone insertion, i.e. in the thinnest and least vascular zone of the
Fig. 4. Biopsy from achilles tendinopathy which is characterized by inflammatory features (peritendinitis): oedema, hyperemia, dilated capillaries and thrombotic phenomena in smaller vessels. (Haematoxylin-eosin, 100!).
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Fig. 5. Biopsy from achilles rupture characterized by fatty degeneration. (Safranin O, 200!).
tendon (Fig. 8). The next most frequent findings are rupture of the proximal portion (near the myotendinous junction) and of the distal end of the tendon. The latter type of rupture usually close to the insertion, disinsertion from the bone surface being an exceptional event. By contrast, fractures due to avulsion of the calcaneal posterior tuberosity are not uncommon, although they cannot be considered as tendon lesions given their nature as real fractures. In recent ruptures, the diastasis usually measures 2–4 cm. The two stumps generally appear frayed, the collagen fibre bundles are interrupted and the empty space is occupied by significant hemorrhage. Where present, the plantar gracilis tendon is nearly always intact (Fig. 8). In inveterate ruptures, the tendon sheath appears thickened and the diastasis commonly measures 5–6 cm. The space between the stumps is occupied by a tendon-like tissue with a diameter smaller than that of normal tendon that is more or less adherent to the two stumps, whose ends may be round and smooth or irregular and rough. Partial ruptures may involve the medial, lateral or central portion of the tendon completely or partially, separately or together with one of both of the other two portions. The rupture may be transverse, oblique or longitudinal. In recent ruptures, the hemorrhagic infiltrate is extensive and dissects
Fig. 6. Biopsy from achilles rupture characterized by areas of cartilage metaplasia. (Haematoxylin-eosin, 400!).
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Fig. 7. Biopsy from achilles rupture characterized by areas of bone metaplasia. (Gomori’s stain, 200!).
into the microtears of fibre bundles [10]. In inveterate cases, a tendon-like tissue is present uniting the two stumps at times masking the rupture.
2. Repair process of tendon lesions Several studies have addressed the morphological, biochemical and biomechanical aspects of the healing process of tendon lesions [21,22]. Several factors affect
Fig. 8. Achilles complete rupture: the site of the rupture lies 5 cm from the bone insertion. The plantar gracilis tendon is intact.
this process favourably or adversely by acting on anabolic and catabolic mechanisms. The healing process is influenced by several matrix fibrillary macromolecules [23]: collagen VI, fibronectin, thrombospondin, laminin, tenascin and elastin. Whereas in normal tendon the presence of collagen VI is negligible, it is considerable in reparative tissue [24]; fibronectin and thrombospondin seem to have an important role in the first organization of the extracellular matrix; laminin appears to have a chemotactic action on neutrophils and mast cells as well as in promoting neoangiogenesis; tenascin may offset the action of fibronectin [25]; elastin seems to stimulate fibroblast proliferation and new vessel formation both in vivo and in vitro [23]. During the tendon repair process, anabolic mechanisms participate in the formation of the matrix and its components with the mediation of collagen, laminin, hyaluronic acid and fibronectin which, through integrins, establish a communication between matrix and cells and are essential for the repair process. Besides anabolic mechanisms, catabolic processes also play an important role by activating enzyme systems that induce matrix rearrangement. A central factor in the healing process is the neurogenic control mediated by substance P and calcitonin gene-related product (CGRP). These neuropeptides induce vasodilation, exudation, neoangiogenesis, neutrophil chemotaxis, and stimulate cell mitosis. Growth factors (PGDF, TGF Beta, EGF, IGF I and II) act specifically on particular cells via surface receptors (integrins); they also exert a non-specific action by affecting cell proliferation, protein synthesis and cell differentiation. In addition, biomechanical factors affect the regulation of repair phenomena, signally by acting on the arrangement and maturation of collagen and elastic fibres [22]. In fact, maturation of the repaired tendon requires adequate mechanical stimuli in terms of intensity and duration. Some aspects of tendon repair are still imperfectly known, like the process of collagen and elastic fibre fibrillogenesis that leads to reconstitution of the tendon tissue. The interactions between biological repair process on one side and suture type and mechanical stimuli on the other are still debated. Although the fibril component of the matrix of normal Achilles tendon has been widely investigated [21,22–26], few studies have addressed fibrillogenesis during tendon repair in different experimental conditions [27,28]. In an experimental investigation of autopsy and animal subjects [19–29], our group described the biological (histological and ultrastructural) and mechanical features of the repair process of tendon lesions. The first phase (inflammation) of the process was seen to be characterized by marked vessel permeability, blood extravasation, hematoma formation, fibrin deposition and appearance of inflammatory cells. The space between the stumps was filled by a lax tissue made up of amorphous matrix, erythrocytes, leucocytes, macrophages and fibroblasts. The ultrastructural
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study showed RER and a well-developed Golgi apparatus. Hyperemia and neoangiogenesis were also detected, as was initial collagen fibrillogenesis with fibrils measuring ˚ . Elastic fibrils were also beginning to form, 200–400 A their filaments measuring 10–12 nm in diameter, without elastin deposition. The inflammatory phase was followed by a hypercellular phase characterized by neovascularization, subsequent fibroblast proliferation (Fig. 9) and synthesis of a matrix that was still not well organized. Fibroblast orientation followed the major tendon axis (Fig. 9). Newly formed collagen fibres were arranged into irregular bundles and ˚ ) compared exhibited an increased diameter (400–600 A with the previous phase. In the hypercellular phase, immature elastic fibrils reached their peak tissue concentration both in relation to normal tissue and to the other phases of the healing process; histometrically, they accounted for about 30% of the surface of the repair tissue. Wide interdigitations were noted between the collagen and the elastic networks. At the end of this phase, the tissue became more compact and most tenocytes and collagen fibres were arranged along the longitudinal axis of the tendon as were immature elastic fibres. In the remodelling phase a better matrix organization was evident, with hypocellularity and restoration of normal vascularization (Fig. 10) and innervation. The characteristic crimps were detected but did not exhibit the periodicity and Fig. 10. Experimental achilles rupture in the rat at 90 days from surgery: the remodelling phase is characterized by a good matrix organization, with hypocellularity and restoration of normal vascularization. The characteristic crimps are detected but do not exhibit the periodicity and amplitude of normal adult tendon tissue. Rare tenocytes are oriented according to the longitudinal tendon axis. (Gomori’s stain, 400!).
Fig. 9. Experimental achilles rupture in the rat at 30 days from surgery: the hypercellular phase is characterized by neovascularization, fibroblast proliferation and a not well organized matrix. Fibroblast orientation follows the major tendon axis. (Gomori’s stain, 400!).
amplitude of normal adult tendon tissue (Fig. 10). Tenocytes were oriented according to the longitudinal tendon axis. ˚ in diameter. In elastic Collagen fibres reached 800–1000 A fibres, elastin deposition was increased and the number of oxytalan fibres reduced. At the end of this phase (6–8 weeks after experimental tenotomy), the tendon had characteristics similar to those of normal tendon (Fig. 10) except for a comparative immaturity of collagen fibres and especially of the elastic fibre system. We also studied the qualitative and quantitative changes in collagen and elastic fibres in the tendon repair process focusing on the relationship between collagen and type of elastic fibre in the various phases of reparative fibrillogenesis [29]. The study of collagen and elastic fibrillogenesis allowed to document significant variations in the type of fibres and in the diameter of the fibrils detected in the various phases. In particular, an elevated number of oxytalan and elaunin fibres was found in the early phases of the healing process. These fibrils exhibited a broad contact with the cellular plasma membrane and diffuse interdigitation with collagen the network. A larger amount of elastin compared with normal tendon tissue was
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synthesized in the subsequent phases, resulting in rapid, albeit partial, maturation of elastic fibres. However, even in the advanced stages of the healing process, the histological features of the reparative tissue were different in quality as well as quantity from those of adult tendon, especially collagen and elastic fibres. Indeed, collagen fibres preserved a diameter similar to the one observed in the early stages of the repair process. Elastic fibres were still immature or partially mature. With reference to the effects of prolonged immobilization, the repair process differed markedly between lesions that had been immobilized and lesions that had been mobilized early. In the latter, fibrillogenesis was considerably accelerated, and collagen and elastic fibres exhibited a better organization and greater diameter. In addition, areas of degeneration and calcification were detected in the cases treated with prolonged immobilization. These experimental observations suggest that mechanical stimuli, particularly early mobilization, have a favourable influence on the regular process of tendon healing and confirm from a biological viewpoint the observations made in biomechanical studies of the repair tissue that early mobilization affords functional advantages over prolonged immobilization [30,31].
3. Conclusion Achilles tendinopathy can be distinguished on the basis of the anatomo-pathological features of the lesion (inflammatory, degenerative, inflammatory-degenerative, metabolic, microtraumatic), the duration of the pathological process (acute or chronic) and its site (tendon, para- and peritendon, insertion). The anatomo-pathological features of Achilles tendinopathy with rupture have been investigated extensively and are supported by bioptic and experimental human studies. Treatments for tendon rupture vary [32–35]; however, a consensus exists on the primary aim of any treatment: to restore the continuity of the tendon to anatomical, histological and biomechanical characteristics resembling as much as possible those of normal tissue with a view to avoiding insufficiency and the recurrence of rupture, which are the main risks whatever the treatment. The study of collagen and elastic fibrillogenesis in different experimental conditions of the repair process shows significant variations in the fibre types and diameter of fibrils present in the various phases of the healing process. In particular, a large number of immature elastic fibrils was detected in the early phases of the process; in later phases a much larger amount of elastin was synthesized compared with normal tissue resulting in maturation, albeit partial, of the elastic fibres involved in cell-matrix interactions (which are essential in any repair and remodelling process). In addition, in tendons mobilized early regeneration can be followed by maturation provided the presence of
appropriate functional stimuli favouring rapid and specific fibrillogenesis with speedy and successful healing of the lesion. Prolonged immobilization may thus adversely affect the morphological and histochemical characteristics of the repaired tissue. Further studies are however required to extrapolate these experimental observations in human pathology and to draw clinical and therapeutic indications.
Acknowledgements The authors wish to thank Dr Silvia Modena for reviewing the English.
References [1] Arandes R, Viladot A. Biomecanica del calcaneo. Med Clin 1953;21: 25–8. [2] de Palma L, Santucci A, Sabetta SP. Anatomia della regione calcaneare. In: Gaggi Aulo, editor. Progressi in medicina e chirurgia del piede fratture del calcagno, Bologna, Italy, vol. 3, 1994. p. 9–21. [3] Kannus P, Jo`zsa L. Histopathologic changes preceding spontaneous rupture of a tendon. J Bone Joint Surg 1991;73A:1507–25. [4] Amstron M, Rausing A. Chronic Achilles tendinopathy. Clin Orthop 1995;316:151–64. [5] William JG. Achilles tendon lesions in sport. Sport Med 1986;3: 114–35. [6] Clement DB, Taunton JE, Smart GW. Achilles tendinitis and peritendinitis: etiology and treatment. Am J Sports Med 1984;12: 179–84. [7] Waterson WS, Maffulli N, Ewen SWB. Subcutaneous rupture of Achilles tendon: basic science and some aspects of clinical practice. Br J Sports Med 1997;31:285–98. [8] Guillet R, Roux R, Genety J. Ruptures of the Achilles tendon in sportsmen. Lyon Chir 1996;62:717–21. [9] Barfred T. Experimental rupture of the achille tendon: comparison of various types of experimental ruptures in rat. Acta Orthop Scand 1971;42:528–43. [10] Perugia l, Postacchini F, Ippolito E. I tendini. In: Italia Masson, editor. Biologia, patologia, clinica, Milano, Italy; 1981. [11] de Palma L, Santucci A, Meme` L, Franzese S. L’interessamento extraarticolare nel piede reumatoide. In: Gaggi Aulo, editor. Progressi in medicina e chirurgia del piede—Il piede reumatico, Bologna, Italy, vol. 11, 2002. p. 65–77. [12] Balasubramiam P, Prathap K. The effect of injection of idrocortisone into rabbit calcaneal tendon. J Bone Joint Surg 1972;54B:729–34. [13] Di Stefano VJ, Nixon JE. Ruptures in Achilles tendon. J Sports Med 1973;1:34–7. [14] Royer RJ, Pierfitte C, Netter P. Features of tendon disorders with fluoroquinolones. Therapie 1994;49:75–6. [15] Wilson AM, Goodship AE. Exercise-induced hyperthermia as a possible mechanism for tendon degenerations. J Biomech 1994;27: 899–905. [16] Arancia G, Trovalusci C, Mariutti G, Mondovi B. Ultrastructural changes induced by hyperthermia in chinese hamster V79 fibroblasts. Int J Hyperthermia 1989;5:341–50. [17] de Palma L, Meme` L, Verdenelli A, Marinelli M. Calcaneodinia nelle sindromi pronatorie. In: Gaggi Aulo, editor. Progressi in medicina e chirurgia del piede—Il dolore calcaneare, Bologna, Italy, vol. 12, 2003. p. 69–75.
L. de Palma et al. / Foot and Ankle Surgery 12 (2006) 5–11 [18] de Palma L, Marinelli M, Meme` L, Pavan M. Immunohistochemistry of the enthesis organ of the human Achilles tendon. Foot Ankle Int 2004;414:418. [19] de Palma L, Gigante A, Rapali S. I processi riparativi delle lesioni tendinee. In: Gaggi Aulo, editor. Progressi in medicina e chirurgia del piede—Il piede nello sport, Bologna, Italy, vol. 7, 1998. p. 13–23. [20] Puddu G, Ippolito E, Postacchini F. A classification of Achilles tendon disease. Am J Sport Med 1976;4:145–50. [21] Amiel D, Frank CB, Hardwood FL, Fronek J, Akeson WH. Tendon and ligaments: a morphological and biochemical comparison. J Orthop Res 1984;1:257–65. [22] Amiel D, Kleiner JB. Biochemistry of tendon and ligament. In: Nimmi ME, Olsen B, editors. Collagen biotechnology, vol. 3. Cleveland, OH: CRC Press; 1988. p. 223–51. [23] Wrenn DS, Griffin GL, Senior RM, Mechan RP. Characterization of biologically active domains on elastin: identification of monoclonal antibody to cell recognition site. Biochemistry 1986;25:5172–6. [24] Murphy PG, Frank CB, Hart DA. The cell biology of ligaments and ligament healing. In: Jackson DW, editor. The anterior cruciate ligament: current and future concepts. New York: Raven Press; 1993. [25] McDevitt CA, Marcelino J. Adhesion macromolecules of the ligament: the molecular glues in wound healing. In: Jackson DW, editor. The anterior cruciate ligament: current and future concepts. New York: Raven Press; 1993. [26] Rowe RWD. The structure of rat tail tendon. Connect Tissue Res 1985;14:9–20.
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[27] Ippolito E, Natali PG, Postacchini F, Accini L, De Martino C. Morphological, immunochemical and biochemical study of rabbit achilles tendon at various age. J Bone Joint Surg 1980;62A:583–98. [28] Postacchini F, De Martino C. Regeneration of rabbit calcaneal tendon maturation of collagen and elastic fibres following partial tenotomy. Connect Tissue Res 1980;8:41–7. [29] Gigante A, Specchia N, Rapali S, Ventura A, de Palma L. Fibrillogenesis in tendon healing: an experimental study. J Biol Res 1996;72:203–11. [30] Best TM, Collins A, Lilly EG, Seaber AV, Goldner RD, Murrel GAC. Achilles tendon healing: a correlation between functional and mechanical performance in the rat. J Orthop Res 1993;11:897–906. [31] Murrel GAC, Lilly EG, Goldner RD, Seaber AV, Best TM. Effects of immobilization of Achilles tendon healing in a rat model. J Orthop Res 1994;12:582–91. [32] Ma GWC, Griffith TG. Percutaneous repair of acute closed rupture Achilles tendon: a new technique. Clin Orthop 1977;128:247–55. [33] McComis GP, Nawoczenski DA, DeHaven KE. Functional bracing for rupture of the Achilles tendon. J Bone Joint Surg 1977;79: 1799–808. [34] Soldatis JJ, Soldatis DB, Goodfellow JH. End-to-end operative repair of Achilles tendon rupture. Am J Sports Med 1997;25:90–5. [35] Chillemi C, Gigante A, Verdenelli A, Marinelli M, Ulisse S, Morgantini A, et al. Percutaneous repair of Achilles tendon rupture: ultrasonographical and isokinetic evaluation. Foot Ankle Surg 2002;8: 267–76.
Physiopathology of the repair process of lesions of Achilles tendon L. de Palma*, A. Gigante, S. Rapali Clinica Ortopedica, Universita` Politecnica delle Marche—Ancona, Ospedali Riuniti Umberto 18-Lancisi-Salesi, Via Conca, 60100 Ancona, Italy Received 15 August 2005; accepted 30 August 2005
Achilles tendinopathy is related to the inflammationdegeneration of the Achilles-calcaneal-plantar system, whose function can be impaired due to a large number of causes. The functional unity of the Achilles-calcaneal-plantar system was demonstrated by Arandes and Viladot as early as 1953 [1]. This system is made up of the triceps surae with the Achilles tendon, the posterior trabecular system of the calcaneal tuberosity and the plantar aponeurosis (Fig. 1), and of some muscles that originate from the calcaneal tuberosity, signally flexor digiti minimi brevis and abductor hallucis medially, flexor digitorum brevis centrally, and abductor digiti minimi laterally [2]. Several factors have been invoked to explain Achilles tendinopathy, including degenerative changes, mechanical factors, iatrogenic causes (e.g. use of corticosteroids and fluoroquinolones), systemic disease (hypercholesterolemia, rheumatoid arthritis, SLE), and hyperthermia. The degeneration hypothesis centres on primitive regressive changes that would progressively weaken the tendon, leading to reduced mechanical resistance and ultimately to spontaneous rupture in normal functional conditions. This hypothesis is supported by degenerative changes found in ruptured Achilles tendons at histology [3, 4]. In addition, studies of autopsy samples and of experimental animals have shown that indirect trauma is unable to induce a subcutaneous lesion of healthy Achilles tendon. Overall, such investigations lend support to the hypothesis that a healthy tendon is unlikely to rupture however intense the functional stress to which it is subjected. According to the mechanical theory, the primitive degenerative changes are insufficient to account for all the * Corresponding author. Tel.: C39 71 5963349; fax: C39 71 5963349. E-mail address: [email protected] (L. de Palma).
causes of tendon rupture, while microtrauma is central to ruptures experienced by young subjects both in the presence and absence of other predisposing factors. The latter are numerous and include: inadequate training footwear [5], muscle fatigue induced by inappropriate training [6,7], and foot biomechanical changes related to particular anatomical conditions. According to Clement and co-workers [6], in the case of muscle fatigue the eccentric action of the gastrocnemius and soleus muscles subjects the tendon to extreme stress that may induce microtears. In addition, non-uniform stress forces applied on different zones of the tendon would favour ischaemic torque phenomena that in turn result in tendon vascular injury [6]. It has also been suggested [8] that a healthy tendon can rupture following forcible muscular exertion solely in the presence of particular anatomical conditions, such as a difference in thickness between muscle and tendon or the absence/insufficiency of the plantar muscle, which has the function to reduce and uniformly distribute the load on the Achilles tendon. Experimental investigations by Barfred and colleagues [9] have demonstrated that if linear traction is applied parallel to the muscle-tendon-bone system, the risk of rupture will involve the whole system uniformly, whereas oblique traction will be more likely to affect the tendon tissue. Such situations can obtain in sports requiring sprinting movements and in some conditions involving biomechanical imbalances of Achilles tendon secondary to particular anatomical conditions of the foot (e.g. pronation syndrome). The observation that 56% of athletes with Achilles tendinopathy overpronate the foot as they walk seems to lend support to this view [6]. These data lead to ascribe a large role to microtrauma in causing the rupture of the Achilles tendon in the absence of primitive degenerative changes. According to this theory, therefore, rupture may
1268-7731/$ - see front matter q 2005 European Foot and Ankle Society. Published by Elsevier Ireland Ltd. All rights reserved. doi:10.1016/j.fas.2005.08.005
6
L. de Palma et al. / Foot and Ankle Surgery 12 (2006) 5–11
Fig. 1. The functional unity of the Achilles-calcaneal-plantar system is made up of the triceps surae with the Achilles tendon, the posterior trabecular system of the calcaneal tuberosity and the plantar aponeurosis.
result from multiple fibril tears due to microtrauma impairing the tendon’s mechanical resistance. Systemic disease (e.g. rheumatoid arthritis, SLE, gout) has been implicated in the pathogenesis of Achilles tendon lesions. However, degenerative changes related to the underlying disease have rarely been observed [10]. For instance, ruptures caused directly by rheumatoid disease are very rare [11], the few existing reports being attributable to the action of proteolytic enzymes released by rheumatoid synovitis of Achilles bursa, to a primitive rheumatoid enthesitis, and to rheumatoid vasculitis with chronic tendon hypoxia. More frequently, the lesion is related to high-dose topical or systemic cortisone administered to treat the disease. An influence of some drugs on degenerative tendon modifications has also been known for some time. Local cortisone causes necrotic changes in tendon tissue [12]. Moreover, reduction of painful symptoms due to the analgesic and anti-inflammatory action of corticosteroids induces patients to subject the tendon to increased functional stress, adding to the degenerative changes and ultimately leading to rupture [13]. Degenerative changes have also been attributed to fluoroquinolones antibiotics [14]. The hyperthermia that develops in the tendon after intense exercise is considered by some researchers as a further cause of tendon degeneration [15]. Wilson and Goodship [15] measured temperatures up to 45 8C following exertion, and Arancia et al. [16] demonstrated fibroblast damage already at 42 8C.
from tendon to bone tissue: (1) tendon; (2) non-calcified fibrocartilage; (3) calcified fibrocartilage; and (4) bone. Zones 2 and 3 are separated by a tidemark (Fig. 2). Achilles insertion tendinopathy is characterized histologically by hyaline degeneration foci evolving to disruption of the tendon tissue and necrosis [19] (Fig. 3). Further typical findings are microtears of the tendon tissue, calcification foci among the tendon fibres, tidemark disruption, thickening of the fibrocartilage layer with presence of hypertrophic chondrocytes and presence of degenerative microcystic cavities containing necrotic material [19]. The pathological involvement of Achilles tendon may exhibit inflammatory (peritendinitis) (Fig. 4), regressive (tendinosis) or, more frequently, mixed features (peritendinitis and tendinosis) [20]. Given the absence of a synovial sheath, tenosynovitic processes are not encountered. Peritendinitis may present in an acute or a chronic form. In the former, the peritenon is affected by an inflammatory process characterized by oedema, hyperemia and formation of a fibrin exudate (Fig. 4). The capillaries appear dilated (Fig. 4) and thrombotic phenomena are observed in smaller vessels. In chronic peritendinitis, increased fibroblast
1. Histological changes The histological changes induced by Achilles tendinopathy can affect the tendon body and/or the bone-tendon calcaneal insertion [17,18]. Achilles insertion tendinopathy is characterized by the inflammatory-degenerative involvement of the bone-tendon junction at the level of calcaneal insertion. In this tendon, the junction is of the direct type, entailing the presence of four distinct zones that can be recognized in the transition
Fig. 2. Achille’s bone-tendon junction. Four distinct zones can be recognized in the transition from tendon to bone tissue: tendon; noncalcified fibrocartilage; calcified fibrocartilage and bone. (Gomori’s stain, 100!).
L. de Palma et al. / Foot and Ankle Surgery 12 (2006) 5–11
Fig. 3. Biopsy from achilles tendinopathy which is characterized by the absence of cells and the presence of hyaline degeneration foci and necrosis. (Safranin O, 200!).
proliferation and adhesion processes are the prevalent findings at pathology [20]. In both acute and chronic forms, the inflammatory process affects the peritenon, largely sparing the tendon tissue. Tendinosis is a degenerative process of the tendon tissue, which may exhibit different anatomo-patologiche changes depending on the nature of regression phenomena. Typical features are changes in the matrix structure with modification of histochemical characteristics and an increased amorphous component. The collagen fibres present signs of degeneration and inhomogeneous fibre thickness. Tenocytes are fewer in number and altered in shape, with loss of the distinctive row arrangement. Vessels are arranged irregularly in the tendon tissue. Different histopathological features are observed in accordance with the characteristics of the degenerative process: hyaline (Fig. 3), mucoid, fibrinoid or fatty degeneration (Fig. 5), areas of calcification and areas of cartilage (Fig. 6) or bone metaplasia (Fig. 7). Matrix regression phenomena eventually impair the tendon’s biomechanical properties, ultimately leading to subcutaneous rupture. In subcutaneous lesions, histological features at the site of rupture change according to time of the examination and lesion severity. In complete rupture, the site of the rupture commonly lies 2–6 cm from the bone insertion, i.e. in the thinnest and least vascular zone of the
Fig. 4. Biopsy from achilles tendinopathy which is characterized by inflammatory features (peritendinitis): oedema, hyperemia, dilated capillaries and thrombotic phenomena in smaller vessels. (Haematoxylin-eosin, 100!).
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Fig. 5. Biopsy from achilles rupture characterized by fatty degeneration. (Safranin O, 200!).
tendon (Fig. 8). The next most frequent findings are rupture of the proximal portion (near the myotendinous junction) and of the distal end of the tendon. The latter type of rupture usually close to the insertion, disinsertion from the bone surface being an exceptional event. By contrast, fractures due to avulsion of the calcaneal posterior tuberosity are not uncommon, although they cannot be considered as tendon lesions given their nature as real fractures. In recent ruptures, the diastasis usually measures 2–4 cm. The two stumps generally appear frayed, the collagen fibre bundles are interrupted and the empty space is occupied by significant hemorrhage. Where present, the plantar gracilis tendon is nearly always intact (Fig. 8). In inveterate ruptures, the tendon sheath appears thickened and the diastasis commonly measures 5–6 cm. The space between the stumps is occupied by a tendon-like tissue with a diameter smaller than that of normal tendon that is more or less adherent to the two stumps, whose ends may be round and smooth or irregular and rough. Partial ruptures may involve the medial, lateral or central portion of the tendon completely or partially, separately or together with one of both of the other two portions. The rupture may be transverse, oblique or longitudinal. In recent ruptures, the hemorrhagic infiltrate is extensive and dissects
Fig. 6. Biopsy from achilles rupture characterized by areas of cartilage metaplasia. (Haematoxylin-eosin, 400!).
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Fig. 7. Biopsy from achilles rupture characterized by areas of bone metaplasia. (Gomori’s stain, 200!).
into the microtears of fibre bundles [10]. In inveterate cases, a tendon-like tissue is present uniting the two stumps at times masking the rupture.
2. Repair process of tendon lesions Several studies have addressed the morphological, biochemical and biomechanical aspects of the healing process of tendon lesions [21,22]. Several factors affect
Fig. 8. Achilles complete rupture: the site of the rupture lies 5 cm from the bone insertion. The plantar gracilis tendon is intact.
this process favourably or adversely by acting on anabolic and catabolic mechanisms. The healing process is influenced by several matrix fibrillary macromolecules [23]: collagen VI, fibronectin, thrombospondin, laminin, tenascin and elastin. Whereas in normal tendon the presence of collagen VI is negligible, it is considerable in reparative tissue [24]; fibronectin and thrombospondin seem to have an important role in the first organization of the extracellular matrix; laminin appears to have a chemotactic action on neutrophils and mast cells as well as in promoting neoangiogenesis; tenascin may offset the action of fibronectin [25]; elastin seems to stimulate fibroblast proliferation and new vessel formation both in vivo and in vitro [23]. During the tendon repair process, anabolic mechanisms participate in the formation of the matrix and its components with the mediation of collagen, laminin, hyaluronic acid and fibronectin which, through integrins, establish a communication between matrix and cells and are essential for the repair process. Besides anabolic mechanisms, catabolic processes also play an important role by activating enzyme systems that induce matrix rearrangement. A central factor in the healing process is the neurogenic control mediated by substance P and calcitonin gene-related product (CGRP). These neuropeptides induce vasodilation, exudation, neoangiogenesis, neutrophil chemotaxis, and stimulate cell mitosis. Growth factors (PGDF, TGF Beta, EGF, IGF I and II) act specifically on particular cells via surface receptors (integrins); they also exert a non-specific action by affecting cell proliferation, protein synthesis and cell differentiation. In addition, biomechanical factors affect the regulation of repair phenomena, signally by acting on the arrangement and maturation of collagen and elastic fibres [22]. In fact, maturation of the repaired tendon requires adequate mechanical stimuli in terms of intensity and duration. Some aspects of tendon repair are still imperfectly known, like the process of collagen and elastic fibre fibrillogenesis that leads to reconstitution of the tendon tissue. The interactions between biological repair process on one side and suture type and mechanical stimuli on the other are still debated. Although the fibril component of the matrix of normal Achilles tendon has been widely investigated [21,22–26], few studies have addressed fibrillogenesis during tendon repair in different experimental conditions [27,28]. In an experimental investigation of autopsy and animal subjects [19–29], our group described the biological (histological and ultrastructural) and mechanical features of the repair process of tendon lesions. The first phase (inflammation) of the process was seen to be characterized by marked vessel permeability, blood extravasation, hematoma formation, fibrin deposition and appearance of inflammatory cells. The space between the stumps was filled by a lax tissue made up of amorphous matrix, erythrocytes, leucocytes, macrophages and fibroblasts. The ultrastructural
L. de Palma et al. / Foot and Ankle Surgery 12 (2006) 5–11
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study showed RER and a well-developed Golgi apparatus. Hyperemia and neoangiogenesis were also detected, as was initial collagen fibrillogenesis with fibrils measuring ˚ . Elastic fibrils were also beginning to form, 200–400 A their filaments measuring 10–12 nm in diameter, without elastin deposition. The inflammatory phase was followed by a hypercellular phase characterized by neovascularization, subsequent fibroblast proliferation (Fig. 9) and synthesis of a matrix that was still not well organized. Fibroblast orientation followed the major tendon axis (Fig. 9). Newly formed collagen fibres were arranged into irregular bundles and ˚ ) compared exhibited an increased diameter (400–600 A with the previous phase. In the hypercellular phase, immature elastic fibrils reached their peak tissue concentration both in relation to normal tissue and to the other phases of the healing process; histometrically, they accounted for about 30% of the surface of the repair tissue. Wide interdigitations were noted between the collagen and the elastic networks. At the end of this phase, the tissue became more compact and most tenocytes and collagen fibres were arranged along the longitudinal axis of the tendon as were immature elastic fibres. In the remodelling phase a better matrix organization was evident, with hypocellularity and restoration of normal vascularization (Fig. 10) and innervation. The characteristic crimps were detected but did not exhibit the periodicity and Fig. 10. Experimental achilles rupture in the rat at 90 days from surgery: the remodelling phase is characterized by a good matrix organization, with hypocellularity and restoration of normal vascularization. The characteristic crimps are detected but do not exhibit the periodicity and amplitude of normal adult tendon tissue. Rare tenocytes are oriented according to the longitudinal tendon axis. (Gomori’s stain, 400!).
Fig. 9. Experimental achilles rupture in the rat at 30 days from surgery: the hypercellular phase is characterized by neovascularization, fibroblast proliferation and a not well organized matrix. Fibroblast orientation follows the major tendon axis. (Gomori’s stain, 400!).
amplitude of normal adult tendon tissue (Fig. 10). Tenocytes were oriented according to the longitudinal tendon axis. ˚ in diameter. In elastic Collagen fibres reached 800–1000 A fibres, elastin deposition was increased and the number of oxytalan fibres reduced. At the end of this phase (6–8 weeks after experimental tenotomy), the tendon had characteristics similar to those of normal tendon (Fig. 10) except for a comparative immaturity of collagen fibres and especially of the elastic fibre system. We also studied the qualitative and quantitative changes in collagen and elastic fibres in the tendon repair process focusing on the relationship between collagen and type of elastic fibre in the various phases of reparative fibrillogenesis [29]. The study of collagen and elastic fibrillogenesis allowed to document significant variations in the type of fibres and in the diameter of the fibrils detected in the various phases. In particular, an elevated number of oxytalan and elaunin fibres was found in the early phases of the healing process. These fibrils exhibited a broad contact with the cellular plasma membrane and diffuse interdigitation with collagen the network. A larger amount of elastin compared with normal tendon tissue was
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synthesized in the subsequent phases, resulting in rapid, albeit partial, maturation of elastic fibres. However, even in the advanced stages of the healing process, the histological features of the reparative tissue were different in quality as well as quantity from those of adult tendon, especially collagen and elastic fibres. Indeed, collagen fibres preserved a diameter similar to the one observed in the early stages of the repair process. Elastic fibres were still immature or partially mature. With reference to the effects of prolonged immobilization, the repair process differed markedly between lesions that had been immobilized and lesions that had been mobilized early. In the latter, fibrillogenesis was considerably accelerated, and collagen and elastic fibres exhibited a better organization and greater diameter. In addition, areas of degeneration and calcification were detected in the cases treated with prolonged immobilization. These experimental observations suggest that mechanical stimuli, particularly early mobilization, have a favourable influence on the regular process of tendon healing and confirm from a biological viewpoint the observations made in biomechanical studies of the repair tissue that early mobilization affords functional advantages over prolonged immobilization [30,31].
3. Conclusion Achilles tendinopathy can be distinguished on the basis of the anatomo-pathological features of the lesion (inflammatory, degenerative, inflammatory-degenerative, metabolic, microtraumatic), the duration of the pathological process (acute or chronic) and its site (tendon, para- and peritendon, insertion). The anatomo-pathological features of Achilles tendinopathy with rupture have been investigated extensively and are supported by bioptic and experimental human studies. Treatments for tendon rupture vary [32–35]; however, a consensus exists on the primary aim of any treatment: to restore the continuity of the tendon to anatomical, histological and biomechanical characteristics resembling as much as possible those of normal tissue with a view to avoiding insufficiency and the recurrence of rupture, which are the main risks whatever the treatment. The study of collagen and elastic fibrillogenesis in different experimental conditions of the repair process shows significant variations in the fibre types and diameter of fibrils present in the various phases of the healing process. In particular, a large number of immature elastic fibrils was detected in the early phases of the process; in later phases a much larger amount of elastin was synthesized compared with normal tissue resulting in maturation, albeit partial, of the elastic fibres involved in cell-matrix interactions (which are essential in any repair and remodelling process). In addition, in tendons mobilized early regeneration can be followed by maturation provided the presence of
appropriate functional stimuli favouring rapid and specific fibrillogenesis with speedy and successful healing of the lesion. Prolonged immobilization may thus adversely affect the morphological and histochemical characteristics of the repaired tissue. Further studies are however required to extrapolate these experimental observations in human pathology and to draw clinical and therapeutic indications.
Acknowledgements The authors wish to thank Dr Silvia Modena for reviewing the English.
References [1] Arandes R, Viladot A. Biomecanica del calcaneo. Med Clin 1953;21: 25–8. [2] de Palma L, Santucci A, Sabetta SP. Anatomia della regione calcaneare. In: Gaggi Aulo, editor. Progressi in medicina e chirurgia del piede fratture del calcagno, Bologna, Italy, vol. 3, 1994. p. 9–21. [3] Kannus P, Jo`zsa L. Histopathologic changes preceding spontaneous rupture of a tendon. J Bone Joint Surg 1991;73A:1507–25. [4] Amstron M, Rausing A. Chronic Achilles tendinopathy. Clin Orthop 1995;316:151–64. [5] William JG. Achilles tendon lesions in sport. Sport Med 1986;3: 114–35. [6] Clement DB, Taunton JE, Smart GW. Achilles tendinitis and peritendinitis: etiology and treatment. Am J Sports Med 1984;12: 179–84. [7] Waterson WS, Maffulli N, Ewen SWB. Subcutaneous rupture of Achilles tendon: basic science and some aspects of clinical practice. Br J Sports Med 1997;31:285–98. [8] Guillet R, Roux R, Genety J. Ruptures of the Achilles tendon in sportsmen. Lyon Chir 1996;62:717–21. [9] Barfred T. Experimental rupture of the achille tendon: comparison of various types of experimental ruptures in rat. Acta Orthop Scand 1971;42:528–43. [10] Perugia l, Postacchini F, Ippolito E. I tendini. In: Italia Masson, editor. Biologia, patologia, clinica, Milano, Italy; 1981. [11] de Palma L, Santucci A, Meme` L, Franzese S. L’interessamento extraarticolare nel piede reumatoide. In: Gaggi Aulo, editor. Progressi in medicina e chirurgia del piede—Il piede reumatico, Bologna, Italy, vol. 11, 2002. p. 65–77. [12] Balasubramiam P, Prathap K. The effect of injection of idrocortisone into rabbit calcaneal tendon. J Bone Joint Surg 1972;54B:729–34. [13] Di Stefano VJ, Nixon JE. Ruptures in Achilles tendon. J Sports Med 1973;1:34–7. [14] Royer RJ, Pierfitte C, Netter P. Features of tendon disorders with fluoroquinolones. Therapie 1994;49:75–6. [15] Wilson AM, Goodship AE. Exercise-induced hyperthermia as a possible mechanism for tendon degenerations. J Biomech 1994;27: 899–905. [16] Arancia G, Trovalusci C, Mariutti G, Mondovi B. Ultrastructural changes induced by hyperthermia in chinese hamster V79 fibroblasts. Int J Hyperthermia 1989;5:341–50. [17] de Palma L, Meme` L, Verdenelli A, Marinelli M. Calcaneodinia nelle sindromi pronatorie. In: Gaggi Aulo, editor. Progressi in medicina e chirurgia del piede—Il dolore calcaneare, Bologna, Italy, vol. 12, 2003. p. 69–75.
L. de Palma et al. / Foot and Ankle Surgery 12 (2006) 5–11 [18] de Palma L, Marinelli M, Meme` L, Pavan M. Immunohistochemistry of the enthesis organ of the human Achilles tendon. Foot Ankle Int 2004;414:418. [19] de Palma L, Gigante A, Rapali S. I processi riparativi delle lesioni tendinee. In: Gaggi Aulo, editor. Progressi in medicina e chirurgia del piede—Il piede nello sport, Bologna, Italy, vol. 7, 1998. p. 13–23. [20] Puddu G, Ippolito E, Postacchini F. A classification of Achilles tendon disease. Am J Sport Med 1976;4:145–50. [21] Amiel D, Frank CB, Hardwood FL, Fronek J, Akeson WH. Tendon and ligaments: a morphological and biochemical comparison. J Orthop Res 1984;1:257–65. [22] Amiel D, Kleiner JB. Biochemistry of tendon and ligament. In: Nimmi ME, Olsen B, editors. Collagen biotechnology, vol. 3. Cleveland, OH: CRC Press; 1988. p. 223–51. [23] Wrenn DS, Griffin GL, Senior RM, Mechan RP. Characterization of biologically active domains on elastin: identification of monoclonal antibody to cell recognition site. Biochemistry 1986;25:5172–6. [24] Murphy PG, Frank CB, Hart DA. The cell biology of ligaments and ligament healing. In: Jackson DW, editor. The anterior cruciate ligament: current and future concepts. New York: Raven Press; 1993. [25] McDevitt CA, Marcelino J. Adhesion macromolecules of the ligament: the molecular glues in wound healing. In: Jackson DW, editor. The anterior cruciate ligament: current and future concepts. New York: Raven Press; 1993. [26] Rowe RWD. The structure of rat tail tendon. Connect Tissue Res 1985;14:9–20.
11
[27] Ippolito E, Natali PG, Postacchini F, Accini L, De Martino C. Morphological, immunochemical and biochemical study of rabbit achilles tendon at various age. J Bone Joint Surg 1980;62A:583–98. [28] Postacchini F, De Martino C. Regeneration of rabbit calcaneal tendon maturation of collagen and elastic fibres following partial tenotomy. Connect Tissue Res 1980;8:41–7. [29] Gigante A, Specchia N, Rapali S, Ventura A, de Palma L. Fibrillogenesis in tendon healing: an experimental study. J Biol Res 1996;72:203–11. [30] Best TM, Collins A, Lilly EG, Seaber AV, Goldner RD, Murrel GAC. Achilles tendon healing: a correlation between functional and mechanical performance in the rat. J Orthop Res 1993;11:897–906. [31] Murrel GAC, Lilly EG, Goldner RD, Seaber AV, Best TM. Effects of immobilization of Achilles tendon healing in a rat model. J Orthop Res 1994;12:582–91. [32] Ma GWC, Griffith TG. Percutaneous repair of acute closed rupture Achilles tendon: a new technique. Clin Orthop 1977;128:247–55. [33] McComis GP, Nawoczenski DA, DeHaven KE. Functional bracing for rupture of the Achilles tendon. J Bone Joint Surg 1977;79: 1799–808. [34] Soldatis JJ, Soldatis DB, Goodfellow JH. End-to-end operative repair of Achilles tendon rupture. Am J Sports Med 1997;25:90–5. [35] Chillemi C, Gigante A, Verdenelli A, Marinelli M, Ulisse S, Morgantini A, et al. Percutaneous repair of Achilles tendon rupture: ultrasonographical and isokinetic evaluation. Foot Ankle Surg 2002;8: 267–76.