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Flexor Tendon Repair
Flexor Tendon Repair Healing, Biomechanics, and Suture Configurations Christopher Myer, MD, John R. Fowler, MD* KEYWORDS Flexor tendon Suture configuration Biomechanics Growth factors Biological augmentation
KEY POINTS Tendon healing is a complex process that must coordinate healing within the tendon while limiting the amount of fibrosis in the surrounding tissues. The ultimate goal of surgical intervention has remained constant: to achieve enough strength to allow early motion, to prevent adhesions within the tendon sheath, and to restore the finger to normal range of motion and function. Although certain suture materials may have superior tensile properties, the number of strands crossing a repair site is the most important factor in the overall strength of the repair. Recent research has been focused on using pharmacologic agents to modify the healing environment to increase the healing response within the tendon while decreasing the adhesion formation between the tendon and its sheath.
Before the 1960s, tendon repairs in the digits were rarely performed because of the universally poor outcomes, particularly in zone II, lending to the term “no man’s land.”1 Sterling Bunnell is often credited as being one of the first to stress the necessity of gentle and precise surgical technique in the treatment of flexor tendon injuries.2 Additional research has focused on different suture configurations or number of core sutures to maximize the strength of tendon repair and postoperative rehabilitation protocols to maximize function.3,4 The ultimate goal of surgical intervention has remained constant: to achieve enough strength to allow early motion, to prevent adhesions within the tendon sheath, and to restore the finger to normal range of motion and function. In recent years, basic science research has focused on biological factors that will increase the tendon
stability after surgical repair, increase intratendinous healing, and decrease extratendinous fibrosis in order to maximize clinical outcomes.5,6 It is in this area that there is the potential for great advancement of our understanding of tendon healing. The purpose of this article is to review the relevant tendon anatomy, biology of tendon healing, biomechanics of tendon healing, biological strategies to augment tendon healing, and suture configurations to maximize strength and motion.
TENDON ANATOMY Tendons are collagen-based tissues that connect muscle to bone. Tendons are primarily composed of type I collagen, whereas the surrounding endotenon and epitenon are primarily composed of type III collagen. Collagen is synthesized and secreted by tenocytes present within the tendon.
Department of Orthopaedics, University of Pittsburgh, Suite 1010, Kaufmann Building, 3471 Fifth Avenue, Pittsburgh, PA 15213, USA * Corresponding author. E-mail address: [email protected] Orthop Clin N Am 47 (2016) 219–226 http://dx.doi.org/10.1016/j.ocl.2015.08.019 0030-5898/16/$ – see front matter Ó 2016 Elsevier Inc. All rights reserved.
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Myer & Fowler Once secreted, the collagen fibers arrange into triple helices and undergo cross-linking to increase their strength and stability.7 The surrounding extracellular matrix (ECM) is thought to help with gliding between collagen fibrils and to provide functional stability to the fibers. The collagen fiber units are bound together by endotenon fascicles. These fascicles bind together within the epitenon to form the tendon (Fig. 1). Lymphatic, vascular, and neural elements are present within the endotenon to supply the fibroblasts. The epitenon contains the blood vessels and tracts for the lymphatics and nerves. The tendon sheath is covered with synovial cells that provide lubrication to aid in gliding of the tendon within the sheath. Outside of the hand, tendons are not typically enclosed within a sheath and are covered by a continuous paratenon that contains the vascular elements to supply the endotenon and epitenon. Both the flexor digitorum profundus (FDP) and flexor digitorum superficialis (FDS) tendons in the digits receive dual nutritional supply from vascular perfusion and synovial diffusion.8,9 The vascular supply is through vincula with each tendon having 2: a longus and a brevis. Proceeding from proximal to distal, the first vinculum encountered is the vinculum longus superficialis (VLS), arising just proximal to the decussation of the FDS and coming off the floor of the digital sheath of the proximal phalanx (Fig. 2). The vinculum brevis superficialis consists of small triangular mesenteries near the insertion of the FDS. The vinculum longus profundus arises from the superficialis at the level of the proximal
interphalangeal (PIP) joint. Finally, the vinculum brevis profundus arises near the insertion of the FDP. Each vinculum inserts on the dorsal aspect of the tendon, creating a richer blood supply on the dorsal side of the tendon. The vincula are important in the repair of injured tendons as they may hold the tendons out to length after injury, and one must be careful not to injure any maintained vincula while repairing an injured tendon, thereby decreasing the already tenuous blood supply. The flexor tendons pass through the carpal canal and then enter a series of pulleys, creating the flexor tendon sheath in the digits. The flexor tendon sheath starts with the first annular pulley, or A1, overlying the metacarpal heads. There are a total of 5 annular pulleys (A1–A5) and 3 cruciate pulleys (C1–C3). The more stout annular pulleys help hold the tendon close to the phalanges, whereas the cruciate pulleys allow for some mobility of the sheath with finger flexion. The tendon sheath needs to be preserved, if at all possible, to maintain the normal function of the repaired tendon. The A1, A3, and A5 pulleys all arise from the volar plates of the metacarpophalangeal, PIP, and distal interphalangeal joints, respectively. These pulleys may be incised and used as windows through which to perform tendon repairs.10 The A2 and A4 pulleys should be maintained to prevent bowstringing of the tendon after repair.
BIOLOGY OF TENDON HEALING Tendon healing is a complex process that must coordinate healing within the tendon while limiting
Fig. 1. Basic tendon structure. Collagen fibrils are bound together to form a collagen fiber. Multiple fibers are surrounded by endotenon in multiple stages to form a tertiary fiber bundle. Several tertiary fiber bundles are bound together by the epitenon to form the tendon. (From Kannus P. Structure of the tendon connective tissue. Scand J Med Sci Sports 2000;10:313; with permission.)
Flexor Tendon Repair Fig. 2. The vascular supply to both flexor tendons is through vincula with each tendon having 2. The FDS receives its supply from the VLS and the vinculum brevis superficialis (VBS). The FDP receives its supply from the vinculum longus profundus (VLP) and the vinculum brevis profundus (VBP). The supply enters the tendons through the dorsal aspect of each tendon. (From Wolfe S, Hotchkiss R, Pederson W, et al. Flexor tendon injury. In: Wolfe S, Hotchkiss R, Pederson W, et al. Green’s operative hand surgery. 6th edition. Philadelphia: Elsevier Churchill Livingstone; 2011; with permission.)
the amount of fibrosis in the surrounding tissues. The initial healing of flexor tendons consists of 3 separate stages: inflammatory, fibroblastic or reparative, and remodeling.10,11 Starting within the first week after injury, blood vessels within the tendon and tendon sheath form a clot at the injury site that is involved in the recruitment of vasodilators and proinflammatory cells.11 These cells migrate to the injury site from both local tissues as well as from distant sites. They also help with removal of necrotic tissue, fibrin clot, and cellular debris through phagocytosis. Canine models have shown that angiogenic factors, such as vascular endothelial growth factor (VEGF), help initiate the vascular invasion to the site of injury.12 In the third week after injury, the tendon enters the fibroblastic stage. In this stage, the fibroblasts rapidly proliferate, synthesize immature collagen in an unorganized manner, and assist with the production of ECM. The initial collagen laid down is type III collagen, a weaker form of collagen than the type I collagen present in native tendons. The combination of type III collagen and previously initiated vascular network leads to scar formation within the tendon, initially decreasing its strength before entering into the final stage of healing. The remodeling stage begins 6 to 8 weeks after injury. In this stage, type I collagen fibers are reoriented in a longitudinal manner along the long axis of the tendon and collagen fibrils begin crosslinking to one another, increasing the strength of the tendon complex. Unfortunately, the end result of the tissue repair never completely mimics the normal native tendon. It is during this stage that adhesions between the tendon and its sheath become more apparent.
Two separate models have been proposed to explain the overall mechanism of tendon healing. Extrinsic healing occurs when the fibroblasts and inflammatory cells move in from outside the tendon and invade the healing site. This process is thought to include the initial formation of adhesions. In contrast, intrinsic healing occurs through the migration of cells from the endotenon and epitenon. In most cases of tendon healing both types are present. Typically the extrinsic mechanism is activated earlier than the intrinsic mechanism and is thought to be responsible for the adhesion formation, whereas the intrinsic system is thought to help with collagen realignment and cross-linking.
BIOMECHANICS OF TENDON HEALING Although primary tendon repair with current techniques maximizes tendon healing and decreases tendon adhesions, it is not currently possible to recreate the biomechanical properties of the normal tendon. Native tendons have a stressstrain curve that is not directly linear in nature. The collagen fibrils are aligned with one another but are not on full tension while at rest. On tensioning of the tendon, there is an initial toe region in which the tendon fibrils fully align with one another (Fig. 3). The curve then follows a linear progression as the tendon is increasingly tensioned. It maintains this linear slope until reaching the failure area of the curve. When tendons initially undergo surgical fixation, they have a decrease in their tension strength. It is not until the sixth to eighth week after repair when the strength of the tendon starts to increase as the collagen fibrils are realigning and the type I collagen begins to replace the initial type III collagen.
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Fig. 3. The collagen fibrils are not fully aligned at rest; once tensioned, the tendon has an initial toe region in which the tendon fibrils fully align with one another. The curve then follows a linear progression as the tendon is increasingly tensioned until it reaches the failure area of the curve.
By starting controlled early active mobilization of the repaired digit, the stress across the repair site is increased. If done at levels below the load to failure of the repair, collagen deposition across the repair site is increased. This benefit, along with the decrease in adhesions between the tendon and its surrounding sheath, is the basis for early mobilization immediately after surgical repair of the tendon or tendons.
BIOLOGICAL STRATEGIES TO AUGMENT TENDON HEALING Careful surgical technique and initiation of early motion after surgical repair of flexor tendon injuries have been the main strategies for decreasing tendon adhesions after surgical repair. However, there has been increased interest in using pharmacologic agents to modify the healing environment. Recent research has been focused on increasing the healing response within the tendon while decreasing the adhesion formation between the tendon and its sheath. Chang13 has performed extensive research into the biomolecular aspect of tendon repair and adhesion formation, studying a variety of growth factors in native tendons, injured tendons, and repaired tendons. The most promising of these growth factors include transforming growth factor b (TGF-B), nuclear factor kappa b (NF-kb), and VEGF.13
Transforming Growth Factor b TGF-b has 3 main isoforms (-b1, -b2, and -b3). It is produced throughout the body by nearly all cell lineages. Chang and colleagues14 have shown that TGF-b1 is present in small amounts in native
tendon and its surrounding sheath and shows a significant increase in production both within the tendon and its surrounding sheath after tendon transection and repair.14 TGF-b1 also seems to be involved in fibrosis and is a focus of manipulation in order to decrease scarring. Shah and colleagues15,16 were able to show that a neutralizing antibody to TFG-b was able to help control scarring in rat dermal wounds. Chang and colleagues17 also demonstrated that the TGF-b neutralizing antibodies were able to increase the total range of motion after flexor tendon repair in a rabbit model. Chang and his group14 then studied the ability to separate 3 separate cell lines (fibroblasts, epitenon tenocytes, and intrinsic tenocytes) and the ability to influence each line separately. The addition of all 3 TGF-b isoforms to the cell cultures created an increase in collagen type I and III production in an in vitro rabbit model. Attempts are currently underway to isolate cells from the surrounding epitenon and selectively limit the expression of TGF-b from these cells after flexor tendon repair.18
Nuclear Factor Kappa b NF-kb is a transcription factor that is found in nearly every cell line, within the cytoplasm of the cells bound to an inhibiting factor. After activation, it releases from the inhibiting factor and passes into the nucleus where it can then bind to and act on the DNA. There are a variety of different ways to activate NF-kb, including bacterial exposure, growth factors, and medications. NF-kb expression is increased after tendon injury and repair, but its exact role in
Flexor Tendon Repair the tendon healing process is still under further investigation.19
were all significantly improved in patients taking ibuprofen.28
Vascular Endothelial Growth Factor
SUTURE CONFIGURATIONS TO MAXIMIZE STRENGTH AND MOTION
VEGF was initially described as a substance that tumors secreted to increase vascular growth; however, it is now known that neutrophils, platelets, keratinocytes, tenocytes, and astrocytes also secrete VEGF.20–22 Most cells produce several different isoforms at the same time, and each of the isoforms has similar end results on the target tissues. After binding to its target, VEGF induces the release of additional growth factors, ultimately causing vasodilation, expression of a-integrins, and the production of interstitial collagenase.23,24 VEGF is present in synovial fibroblasts. Pufe and colleagues25 showed that VEGF was present at very low levels in native Achilles tendons, and its expression increased after injury. Others have shown increases in VEGF mRNA levels after flexor tendon injury and repair.12 If investigators are able to harness the VEGF production and direct it where necessary, it may be possible to increase the vascular inflow to the tenuous blood supply that currently limits flexor tendon healing.
Nonsteroidal Antiinflammatory Medications Nonsteroidal antiinflammatories (NSAIDs) are a class of medication that functions by inhibition of the cyclooxygenase (COX) enzyme, thereby inhibiting prostaglandin biosynthesis.26 There are 2 distinct isoforms of the COX enzyme, COX-1 and COX-2. COX-1 is the constitutive form, and its activation leads to the production of prostacyclin. Prostacyclin is antithrombogenic and is cytoprotective when released by the gastric mucosa. COX-2 is an inducible isoform that is stimulated by other inflammatory stimuli and cytokines. A recent animal study has shown that ibuprofen is more effective than COX-2 inhibitors and placebo in decreasing adhesion formation. The investigators transected and then repaired tendons in rabbit forepaws and then treated the rabbits with placebo, ibuprofen, or rofecoxib. At 12 weeks, the rabbits treated with ibuprofen had significantly greater range of motion than both placebo and rofecoxib (P 5 .009).27 A human study has shown that ibuprofen seems to improve range of motion of the involved fingers after flexor tendon injury. Patients with zone II flexor tendon laceration repairs were randomized into either placebo or high-dose ibuprofen (2400 mg/d) for 1 month. Total active motion (TAM) at 4 weeks, TAM at 12 weeks, flexion contracture at 3 months, and disabilities of the arm, shoulder, and hand scores at 3 months
Although many different suture materials and configurations have been developed over the years, there are several core principles that need to be maintained in order to obtain stable fixation of the tendon ends. These principles include using a core suture that goes through the ends of the tendons combined with an epitendinous suture to prevent gapping at the repair site. The strength of the repair is directly proportional to the size of the suture as well as the number of passes across the repair site. More dorsal placement of the core suture provides greater strength to the construct when compared with a slightly more volar placement of the core suture.29 Increasing the size of the core suture leads to both increased strength of the repair as well as a decrease in gap formation. Barrie and colleagues30 showed in a cadaveric study that 3-0 sutures lead to a 2- to 3-fold increase in fatigue strength when compared with 4-0 sutures. In that same study, they compared variations of 2- and 4-strand flexor tendon repairs using nonlocked, simple locked, and cross-stitch locked patterns. The 3-0 four-strand cross-stitch locked repair had significantly greater fatigue strength than all other repairs tested. Additionally, all repairs using 4-0 sutures failed secondary to suture rupture, whereas repairs using 3-0 most commonly failed through suture pullout. In contrast, Osei and colleagues31 demonstrated that even though the cross-sectional area of the 3-0 polyfilament caprolactam suture is 42% greater than that of the 4-0 polyfilament caprolactam, an 8-strand 4-0 suture repair was 43% stronger than a 4-strand 3-0 suture repair. A major conclusion from this study was that, although certain suture materials may have superior tensile properties, the number of strands crossing a repair site likely plays a larger role in the overall strength of the repair. Lawrence and colleagues32 demonstrated that changing the strength and stiffness of the suture material also affects gap formation. By using a stiffer and stronger material, such as Fiberwire (Arthrex) or stainless steel, the amount of gap formation at the repair site is decreased when comparing equal diameter suture. Fiberwire was shown to withstand greater ultimate forces and have a greater load to gap formation when compared with nylon, Prolene, (Ethicon) and Ethibond (Ethicon).33 In addition, Scherman and colleagues33 showed us that not all sutures are
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Myer & Fowler created equal. By taking cross-sectional areas of Fiberwire, Prolene, and Ticron (Covidien), of both 3-0 and 4-0 caliber, they were able to show that the 3-0 Fiberwire was larger in cross-sectional area than both 3-0 Prolene and 3-0 Ticron. They also were able to show that 4-0 Fiberwire was larger in cross-sectional area than 3-0 Prolene and 3-0 Ticron. The difference in true cross-sectional area of different sutures is something that most surgeons are not aware of and must be kept in mind when choosing sutures for flexor tendon repair. The purchase of the core suture has also been extensively studied. Several in vitro animal studies have shown that the distance from the cut tendon end can significantly influence the strength of the repair. These studies have also shown that the optimal length for the purchase of the core suture is between 7 and 12 mm. With a purchase less than 7 mm, the strength decreases significantly, whereas the purchase greater than 12 mm adds little to no strength to the construct.34,35 The type of suture used, the size of the suture used, and the number of strands across the repair site are not the only factors associated with increased strength and decreased gapping at the repair site. Wu and colleagues36 found that asymmetry in the repair can also increase the strength and decrease gapping. Creating a repair in which the purchase of 2 separate modified Kessler stitches, one with a purchase length of 8 mm on one side and 12 mm on the other and the second stitch is a mirror image reversing the sides for the 8- and 12-mm purchase, created a construct that was shown to have decreased gapping at initial loading as well as after cyclical loading when compared with symmetric repairs with a purchase length of 10 or 12 mm from the laceration. Using an epitendinous suture increases the strength of the repair. Traditionally, either a 5-0 or 6-0 monofilament suture has been used. Several studies have shown that some form of cross-stitch or interlocking horizontal mattress decreases gliding resistance and increases the maximal strength of the repair construct.37 In an attempt to increase the strength of the repair and improve surgical times, fibrin glue has been used to augment the repair. A direct comparison was performed between repairs that were augmented with an epitendinous suture and repairs augmented with fibrin glue. The linear stiffness, force to produce a 2-mm gap, and ultimate failure were similar between the two groups, whereas the fibrin glue repair had an increased gliding resistance when compared with the epitendinous repair.38 Based on this information, an epitendinous suture adds strength, decreases gap formation, and improves the overall construct
created with the tendon repair and should be used whenever possible. Hwang and colleagues39 showed that repairing the FDP and both slips of the FDS increases the work of flexion by 51%, whereas repairing the FDP alone increased the work by 21%. Repairing only one slip of the FDS increased the work by an additional 9%. Because of this, one may feel comfortable with only repairing one slip of the FDS if it improves gliding of the flexor tendons through their flexor sheath without compromising the patients’ outcomes.
SUMMARY Flexor tendon healing is a complex collaboration between the tendons and their surrounding milieu. The goal is to increase the strength of the repair construct to allow for appropriate tendon healing while minimizing the scar formation to the surrounding tissues. By preserving the blood supply to the tendon through its vincula, we can maintain the nutrients needed for tendon healing. The first stage of tendon healing relies on an initial inflammatory response; with the possibility of increasing the effectiveness and decreasing the side effects of biological factors, such as TGF-b, NF-kb, and VEGF, we may be able to tilt the balance of tendon healing and adhesion formation in our favor. The use of simple and safe medications, such as NSAIDs, may also help with the battle between healing and scar. Using an appropriate construct when repairing an injured tendon aids in the ability to mobilize the digits, which also aids in decreasing adhesion formation. Using at least a 4-strand repair, of either a 3-0 or 4-0 suture with a purchase length of 7 to 12 mm, is necessary to allow for early active motion of the injured digits. By adding an epitendonous suture, we can both increase the strength of the repair as well as decrease the gliding resistance of the repair site. This construct allows for early passive motion while decreasing the chance of gap formation, which should allow for appropriate healing of the tendon while limiting the adhesion formation with the tendon sheath.
REFERENCES 1. Kleinert H, Kutz J, Ashbell T, et al. Primary repair of lacerated flexor tendons in “no man’s land.” J Bone Joint Surg Am 1967;49:577. 2. Wolfe S, Hotchkiss R, Pederson W, et al. Green’s operative hand surgery. 6th edition. Philadelphia: Elsevier Churchill Livingstone; 2011. 3. Lister GD, Kleinert HE, Kutz JE, et al. Primary flexor tendon repair followed by immediate controlled mobilization. J Hand Surg Am 1977;2(6):441–51.
Flexor Tendon Repair 4. Duran RJ, Houser RG, Coleman CR, et al. A preliminary report in the use of controlled passive motion following flexor tendon repair in zones II and III. J Hand Surg Am 1976;1:79. 5. Strickland JW. Flexor tendon injuries, I: foundations of treatment. J Am Acad Orthop Surg 1995;3: 44–54. 6. Strickland JW. Flexor tendon injuries, II: operative technique. J Am Acad Orthop Surg 1995;3:55–62. 7. Kuhn K. The structure of collagen. Essays Biochem 1969;5:59–87. 8. Ochiai N, Matsui T, Miyaji N, et al. Vascular anatomy of flexor tendons. I. Vincular system and blood supply of the profundus tendon in the digital sheath. J Hand Surg Am 1979;4(4):321–30. 9. Lundborg G, Rank F. Experimental intrinsic healing of flexor tendons based upon synovial fluid nutrition. J Hand Surg Am 1978;3(1):21–31. 10. Seiler JG. Flexor tendon repair. J Am Soc Surg Hand 2001;1(3):177–91. 11. Gelberman RH, Vandeberg JS, Manske PR, et al. The early stages of flexor tendon healing: a morphologic study of the first fourteen days. J Hand Surg Am 1985;10(6):776–84. 12. Bidder M, Towler DA, Gelberman RH, et al. Expression of mRNA for vascular endothelial growth factor at the repair site of healing canine flexor tendon. J Orthop Res 2000;18:247–52. 13. Chang J. Studies in flexor tendon reconstruction: biomolecular modulation of tendon repair and tissue engineering. J Hand Surg Am 2012;37: 552–61. 14. Chang J, Most D, Stelnicki E, et al. Gene expression of transforming growth factor beta-1 in rabbit zone II flexor tendon wound healing: evidence for dual mechanisms of repair. Plast Reconstr Surg 1997; 100(4):937–44. 15. Shah M, Foreman DM, Ferguson MWJ. Control of scarring in adult wounds by neutralising antibody to transforming growth factor beta. Lancet 1992; 339:213–4. 16. Shah M, Foreman DM, Ferguson MWJ. Neutralisation of TGF-B1 and TGF-B2 or exogenous addition of TGF-B3 to cutaneous rat wounds reduces scarring. J Cell Sci 2005;108:985–1002. 17. Chang J, Thunder R, Most D, et al. Studies in flexor tendon wound healing: neutralizing antibody to TGFB1 increases post-operative range of motion. Plast Reconstr Surg 2000;105:148–55. 18. Klein MB, Yalamanchi N, Pham H, et al. Flexor tendon healing in vitro: effects of TGF-beta on tendon cell collagen production. J Hand Surg Am 2002;27:615–20. 19. Tang JB, Xu X, Ding F, et al. Expression of genes for collagen production and NF-kB gene activation of in vivo healing flexor tendons. J Hand Surg Am 2004;29:564–70.
20. McCourt M, Wang JH, Sookhai S, et al. Proinflammatory mediators stimulate neutrophil-directed angiogenesis. Arch Surg 1999;134:1325–32. 21. Weltermann A, Wolzt M, Petersmann K, et al. Large amounts of vascular endothelial growth factor at the site of hemostatic plug formation in vivo. Arterioscler Thromb Vasc Biol 1999;19:1757–60. 22. Shweiki D, Itin A, Soffer D, et al. Vascular endothelial growth factor induced by hypoxia may mediate hypoxia-initiated angiogenesis. Nature 1992;359: 843–5. 23. Unemori EN, Ferrara N, Bauer EA, et al. Vascular endothelial growth factor induces interstitial collagenase expression in human endothelial cells. J Cell Physiol 1992;153:557–62. 24. Dvorak HF. VPF/VEGF and the angiogenic response. Semin Perinatol 2000;24:75–8. 25. Pufe T, Petersen W, Tillmann B, et al. The angiogenic peptide vascular endothelial growth factor is expressed in foetal and ruptured tendons. Virchows Arch 2001;439:579–85. 26. Vane JR, Botting RM. Mechanism of action of nonsteroidal anti-inflammatory drugs. Am J Med 1998;104(3):2S–8S. 27. Tan V, Nourbakhsh A, Capo J, et al. Effects of nonsteroidal anti-inflammatory drugs on flexor tendon adhesion. J Hand Surg Am 2010;35:941–7. 28. Rouhani A, Tabrizi A, Ghavidel E. Effects of nonsteroidal anti-inflammatory drugs on flexor tendon rehabilitation after repair. Arch Bone Jt Surg 2013; 1(1):28–30. 29. Soejima O, Diao E, Lotz JC, et al. Comparative mechanical analysis of dorsal versus palmar placement of core suture for flexor tendon repairs. J Hand Surg Am 1995;20:801–7. 30. Barrie KA, Tomak SL, Cholewicki J, et al. Effect of suture locking and suture caliber on fatigue strength of flexor tendon repairs. J Hand Surg Am 2001;26: 340–6. 31. Osei DA, Stepan JG, Calfee RP, et al. The effect of suture caliber and number of core suture strands on zone ii flexor tendon repair: a study in human cadavers. J Hand Surg Am 2014;39(2):262–8. 32. Lawrence TM, Davis TRC. A biomechanical analysis of suture materials and their influence on a fourstrand flexor tendon repair. J Hand Surg Am 2005; 30:836–41. 33. Scherman P, Haddad R, Scougall P, et al. Crosssectional area and strength differences of fiberwire, prolene, and ticron sutures. J Hand Surg Am 2010; 35:780–4. 34. Cao Y, Zhu B, Xie RG, et al. Influence of core suture purchase length on strength of four-strand tendon repairs. J Hand Surg Am 2006;31(1):107–12. 35. Tang JB, Zhang Y, Cao Y, et al. Core suture purchase affects strength of tendon repairs. J Hand Surg Am 2005;30:1262–6.
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38. Xu NM, Brown PJ, Plate JF, et al. Fibrin glue augmentation for flexor tendon repair increases friction compared with epitendinous suture. J Hand Surg Am 2013;38(12):2329–34. 39. Hwang MD, Pettrone S, Trumble TE. Work of flexion related to different suture materials after flexor digitorum profundus and flexor digitorum superficialis tendon repair in zone II: a biomechanical study. J Hand Surg Am 2009;34:700–4.
KEY POINTS Tendon healing is a complex process that must coordinate healing within the tendon while limiting the amount of fibrosis in the surrounding tissues. The ultimate goal of surgical intervention has remained constant: to achieve enough strength to allow early motion, to prevent adhesions within the tendon sheath, and to restore the finger to normal range of motion and function. Although certain suture materials may have superior tensile properties, the number of strands crossing a repair site is the most important factor in the overall strength of the repair. Recent research has been focused on using pharmacologic agents to modify the healing environment to increase the healing response within the tendon while decreasing the adhesion formation between the tendon and its sheath.
Before the 1960s, tendon repairs in the digits were rarely performed because of the universally poor outcomes, particularly in zone II, lending to the term “no man’s land.”1 Sterling Bunnell is often credited as being one of the first to stress the necessity of gentle and precise surgical technique in the treatment of flexor tendon injuries.2 Additional research has focused on different suture configurations or number of core sutures to maximize the strength of tendon repair and postoperative rehabilitation protocols to maximize function.3,4 The ultimate goal of surgical intervention has remained constant: to achieve enough strength to allow early motion, to prevent adhesions within the tendon sheath, and to restore the finger to normal range of motion and function. In recent years, basic science research has focused on biological factors that will increase the tendon
stability after surgical repair, increase intratendinous healing, and decrease extratendinous fibrosis in order to maximize clinical outcomes.5,6 It is in this area that there is the potential for great advancement of our understanding of tendon healing. The purpose of this article is to review the relevant tendon anatomy, biology of tendon healing, biomechanics of tendon healing, biological strategies to augment tendon healing, and suture configurations to maximize strength and motion.
TENDON ANATOMY Tendons are collagen-based tissues that connect muscle to bone. Tendons are primarily composed of type I collagen, whereas the surrounding endotenon and epitenon are primarily composed of type III collagen. Collagen is synthesized and secreted by tenocytes present within the tendon.
Department of Orthopaedics, University of Pittsburgh, Suite 1010, Kaufmann Building, 3471 Fifth Avenue, Pittsburgh, PA 15213, USA * Corresponding author. E-mail address: [email protected] Orthop Clin N Am 47 (2016) 219–226 http://dx.doi.org/10.1016/j.ocl.2015.08.019 0030-5898/16/$ – see front matter Ó 2016 Elsevier Inc. All rights reserved.
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INTRODUCTION
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Myer & Fowler Once secreted, the collagen fibers arrange into triple helices and undergo cross-linking to increase their strength and stability.7 The surrounding extracellular matrix (ECM) is thought to help with gliding between collagen fibrils and to provide functional stability to the fibers. The collagen fiber units are bound together by endotenon fascicles. These fascicles bind together within the epitenon to form the tendon (Fig. 1). Lymphatic, vascular, and neural elements are present within the endotenon to supply the fibroblasts. The epitenon contains the blood vessels and tracts for the lymphatics and nerves. The tendon sheath is covered with synovial cells that provide lubrication to aid in gliding of the tendon within the sheath. Outside of the hand, tendons are not typically enclosed within a sheath and are covered by a continuous paratenon that contains the vascular elements to supply the endotenon and epitenon. Both the flexor digitorum profundus (FDP) and flexor digitorum superficialis (FDS) tendons in the digits receive dual nutritional supply from vascular perfusion and synovial diffusion.8,9 The vascular supply is through vincula with each tendon having 2: a longus and a brevis. Proceeding from proximal to distal, the first vinculum encountered is the vinculum longus superficialis (VLS), arising just proximal to the decussation of the FDS and coming off the floor of the digital sheath of the proximal phalanx (Fig. 2). The vinculum brevis superficialis consists of small triangular mesenteries near the insertion of the FDS. The vinculum longus profundus arises from the superficialis at the level of the proximal
interphalangeal (PIP) joint. Finally, the vinculum brevis profundus arises near the insertion of the FDP. Each vinculum inserts on the dorsal aspect of the tendon, creating a richer blood supply on the dorsal side of the tendon. The vincula are important in the repair of injured tendons as they may hold the tendons out to length after injury, and one must be careful not to injure any maintained vincula while repairing an injured tendon, thereby decreasing the already tenuous blood supply. The flexor tendons pass through the carpal canal and then enter a series of pulleys, creating the flexor tendon sheath in the digits. The flexor tendon sheath starts with the first annular pulley, or A1, overlying the metacarpal heads. There are a total of 5 annular pulleys (A1–A5) and 3 cruciate pulleys (C1–C3). The more stout annular pulleys help hold the tendon close to the phalanges, whereas the cruciate pulleys allow for some mobility of the sheath with finger flexion. The tendon sheath needs to be preserved, if at all possible, to maintain the normal function of the repaired tendon. The A1, A3, and A5 pulleys all arise from the volar plates of the metacarpophalangeal, PIP, and distal interphalangeal joints, respectively. These pulleys may be incised and used as windows through which to perform tendon repairs.10 The A2 and A4 pulleys should be maintained to prevent bowstringing of the tendon after repair.
BIOLOGY OF TENDON HEALING Tendon healing is a complex process that must coordinate healing within the tendon while limiting
Fig. 1. Basic tendon structure. Collagen fibrils are bound together to form a collagen fiber. Multiple fibers are surrounded by endotenon in multiple stages to form a tertiary fiber bundle. Several tertiary fiber bundles are bound together by the epitenon to form the tendon. (From Kannus P. Structure of the tendon connective tissue. Scand J Med Sci Sports 2000;10:313; with permission.)
Flexor Tendon Repair Fig. 2. The vascular supply to both flexor tendons is through vincula with each tendon having 2. The FDS receives its supply from the VLS and the vinculum brevis superficialis (VBS). The FDP receives its supply from the vinculum longus profundus (VLP) and the vinculum brevis profundus (VBP). The supply enters the tendons through the dorsal aspect of each tendon. (From Wolfe S, Hotchkiss R, Pederson W, et al. Flexor tendon injury. In: Wolfe S, Hotchkiss R, Pederson W, et al. Green’s operative hand surgery. 6th edition. Philadelphia: Elsevier Churchill Livingstone; 2011; with permission.)
the amount of fibrosis in the surrounding tissues. The initial healing of flexor tendons consists of 3 separate stages: inflammatory, fibroblastic or reparative, and remodeling.10,11 Starting within the first week after injury, blood vessels within the tendon and tendon sheath form a clot at the injury site that is involved in the recruitment of vasodilators and proinflammatory cells.11 These cells migrate to the injury site from both local tissues as well as from distant sites. They also help with removal of necrotic tissue, fibrin clot, and cellular debris through phagocytosis. Canine models have shown that angiogenic factors, such as vascular endothelial growth factor (VEGF), help initiate the vascular invasion to the site of injury.12 In the third week after injury, the tendon enters the fibroblastic stage. In this stage, the fibroblasts rapidly proliferate, synthesize immature collagen in an unorganized manner, and assist with the production of ECM. The initial collagen laid down is type III collagen, a weaker form of collagen than the type I collagen present in native tendons. The combination of type III collagen and previously initiated vascular network leads to scar formation within the tendon, initially decreasing its strength before entering into the final stage of healing. The remodeling stage begins 6 to 8 weeks after injury. In this stage, type I collagen fibers are reoriented in a longitudinal manner along the long axis of the tendon and collagen fibrils begin crosslinking to one another, increasing the strength of the tendon complex. Unfortunately, the end result of the tissue repair never completely mimics the normal native tendon. It is during this stage that adhesions between the tendon and its sheath become more apparent.
Two separate models have been proposed to explain the overall mechanism of tendon healing. Extrinsic healing occurs when the fibroblasts and inflammatory cells move in from outside the tendon and invade the healing site. This process is thought to include the initial formation of adhesions. In contrast, intrinsic healing occurs through the migration of cells from the endotenon and epitenon. In most cases of tendon healing both types are present. Typically the extrinsic mechanism is activated earlier than the intrinsic mechanism and is thought to be responsible for the adhesion formation, whereas the intrinsic system is thought to help with collagen realignment and cross-linking.
BIOMECHANICS OF TENDON HEALING Although primary tendon repair with current techniques maximizes tendon healing and decreases tendon adhesions, it is not currently possible to recreate the biomechanical properties of the normal tendon. Native tendons have a stressstrain curve that is not directly linear in nature. The collagen fibrils are aligned with one another but are not on full tension while at rest. On tensioning of the tendon, there is an initial toe region in which the tendon fibrils fully align with one another (Fig. 3). The curve then follows a linear progression as the tendon is increasingly tensioned. It maintains this linear slope until reaching the failure area of the curve. When tendons initially undergo surgical fixation, they have a decrease in their tension strength. It is not until the sixth to eighth week after repair when the strength of the tendon starts to increase as the collagen fibrils are realigning and the type I collagen begins to replace the initial type III collagen.
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Fig. 3. The collagen fibrils are not fully aligned at rest; once tensioned, the tendon has an initial toe region in which the tendon fibrils fully align with one another. The curve then follows a linear progression as the tendon is increasingly tensioned until it reaches the failure area of the curve.
By starting controlled early active mobilization of the repaired digit, the stress across the repair site is increased. If done at levels below the load to failure of the repair, collagen deposition across the repair site is increased. This benefit, along with the decrease in adhesions between the tendon and its surrounding sheath, is the basis for early mobilization immediately after surgical repair of the tendon or tendons.
BIOLOGICAL STRATEGIES TO AUGMENT TENDON HEALING Careful surgical technique and initiation of early motion after surgical repair of flexor tendon injuries have been the main strategies for decreasing tendon adhesions after surgical repair. However, there has been increased interest in using pharmacologic agents to modify the healing environment. Recent research has been focused on increasing the healing response within the tendon while decreasing the adhesion formation between the tendon and its sheath. Chang13 has performed extensive research into the biomolecular aspect of tendon repair and adhesion formation, studying a variety of growth factors in native tendons, injured tendons, and repaired tendons. The most promising of these growth factors include transforming growth factor b (TGF-B), nuclear factor kappa b (NF-kb), and VEGF.13
Transforming Growth Factor b TGF-b has 3 main isoforms (-b1, -b2, and -b3). It is produced throughout the body by nearly all cell lineages. Chang and colleagues14 have shown that TGF-b1 is present in small amounts in native
tendon and its surrounding sheath and shows a significant increase in production both within the tendon and its surrounding sheath after tendon transection and repair.14 TGF-b1 also seems to be involved in fibrosis and is a focus of manipulation in order to decrease scarring. Shah and colleagues15,16 were able to show that a neutralizing antibody to TFG-b was able to help control scarring in rat dermal wounds. Chang and colleagues17 also demonstrated that the TGF-b neutralizing antibodies were able to increase the total range of motion after flexor tendon repair in a rabbit model. Chang and his group14 then studied the ability to separate 3 separate cell lines (fibroblasts, epitenon tenocytes, and intrinsic tenocytes) and the ability to influence each line separately. The addition of all 3 TGF-b isoforms to the cell cultures created an increase in collagen type I and III production in an in vitro rabbit model. Attempts are currently underway to isolate cells from the surrounding epitenon and selectively limit the expression of TGF-b from these cells after flexor tendon repair.18
Nuclear Factor Kappa b NF-kb is a transcription factor that is found in nearly every cell line, within the cytoplasm of the cells bound to an inhibiting factor. After activation, it releases from the inhibiting factor and passes into the nucleus where it can then bind to and act on the DNA. There are a variety of different ways to activate NF-kb, including bacterial exposure, growth factors, and medications. NF-kb expression is increased after tendon injury and repair, but its exact role in
Flexor Tendon Repair the tendon healing process is still under further investigation.19
were all significantly improved in patients taking ibuprofen.28
Vascular Endothelial Growth Factor
SUTURE CONFIGURATIONS TO MAXIMIZE STRENGTH AND MOTION
VEGF was initially described as a substance that tumors secreted to increase vascular growth; however, it is now known that neutrophils, platelets, keratinocytes, tenocytes, and astrocytes also secrete VEGF.20–22 Most cells produce several different isoforms at the same time, and each of the isoforms has similar end results on the target tissues. After binding to its target, VEGF induces the release of additional growth factors, ultimately causing vasodilation, expression of a-integrins, and the production of interstitial collagenase.23,24 VEGF is present in synovial fibroblasts. Pufe and colleagues25 showed that VEGF was present at very low levels in native Achilles tendons, and its expression increased after injury. Others have shown increases in VEGF mRNA levels after flexor tendon injury and repair.12 If investigators are able to harness the VEGF production and direct it where necessary, it may be possible to increase the vascular inflow to the tenuous blood supply that currently limits flexor tendon healing.
Nonsteroidal Antiinflammatory Medications Nonsteroidal antiinflammatories (NSAIDs) are a class of medication that functions by inhibition of the cyclooxygenase (COX) enzyme, thereby inhibiting prostaglandin biosynthesis.26 There are 2 distinct isoforms of the COX enzyme, COX-1 and COX-2. COX-1 is the constitutive form, and its activation leads to the production of prostacyclin. Prostacyclin is antithrombogenic and is cytoprotective when released by the gastric mucosa. COX-2 is an inducible isoform that is stimulated by other inflammatory stimuli and cytokines. A recent animal study has shown that ibuprofen is more effective than COX-2 inhibitors and placebo in decreasing adhesion formation. The investigators transected and then repaired tendons in rabbit forepaws and then treated the rabbits with placebo, ibuprofen, or rofecoxib. At 12 weeks, the rabbits treated with ibuprofen had significantly greater range of motion than both placebo and rofecoxib (P 5 .009).27 A human study has shown that ibuprofen seems to improve range of motion of the involved fingers after flexor tendon injury. Patients with zone II flexor tendon laceration repairs were randomized into either placebo or high-dose ibuprofen (2400 mg/d) for 1 month. Total active motion (TAM) at 4 weeks, TAM at 12 weeks, flexion contracture at 3 months, and disabilities of the arm, shoulder, and hand scores at 3 months
Although many different suture materials and configurations have been developed over the years, there are several core principles that need to be maintained in order to obtain stable fixation of the tendon ends. These principles include using a core suture that goes through the ends of the tendons combined with an epitendinous suture to prevent gapping at the repair site. The strength of the repair is directly proportional to the size of the suture as well as the number of passes across the repair site. More dorsal placement of the core suture provides greater strength to the construct when compared with a slightly more volar placement of the core suture.29 Increasing the size of the core suture leads to both increased strength of the repair as well as a decrease in gap formation. Barrie and colleagues30 showed in a cadaveric study that 3-0 sutures lead to a 2- to 3-fold increase in fatigue strength when compared with 4-0 sutures. In that same study, they compared variations of 2- and 4-strand flexor tendon repairs using nonlocked, simple locked, and cross-stitch locked patterns. The 3-0 four-strand cross-stitch locked repair had significantly greater fatigue strength than all other repairs tested. Additionally, all repairs using 4-0 sutures failed secondary to suture rupture, whereas repairs using 3-0 most commonly failed through suture pullout. In contrast, Osei and colleagues31 demonstrated that even though the cross-sectional area of the 3-0 polyfilament caprolactam suture is 42% greater than that of the 4-0 polyfilament caprolactam, an 8-strand 4-0 suture repair was 43% stronger than a 4-strand 3-0 suture repair. A major conclusion from this study was that, although certain suture materials may have superior tensile properties, the number of strands crossing a repair site likely plays a larger role in the overall strength of the repair. Lawrence and colleagues32 demonstrated that changing the strength and stiffness of the suture material also affects gap formation. By using a stiffer and stronger material, such as Fiberwire (Arthrex) or stainless steel, the amount of gap formation at the repair site is decreased when comparing equal diameter suture. Fiberwire was shown to withstand greater ultimate forces and have a greater load to gap formation when compared with nylon, Prolene, (Ethicon) and Ethibond (Ethicon).33 In addition, Scherman and colleagues33 showed us that not all sutures are
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Myer & Fowler created equal. By taking cross-sectional areas of Fiberwire, Prolene, and Ticron (Covidien), of both 3-0 and 4-0 caliber, they were able to show that the 3-0 Fiberwire was larger in cross-sectional area than both 3-0 Prolene and 3-0 Ticron. They also were able to show that 4-0 Fiberwire was larger in cross-sectional area than 3-0 Prolene and 3-0 Ticron. The difference in true cross-sectional area of different sutures is something that most surgeons are not aware of and must be kept in mind when choosing sutures for flexor tendon repair. The purchase of the core suture has also been extensively studied. Several in vitro animal studies have shown that the distance from the cut tendon end can significantly influence the strength of the repair. These studies have also shown that the optimal length for the purchase of the core suture is between 7 and 12 mm. With a purchase less than 7 mm, the strength decreases significantly, whereas the purchase greater than 12 mm adds little to no strength to the construct.34,35 The type of suture used, the size of the suture used, and the number of strands across the repair site are not the only factors associated with increased strength and decreased gapping at the repair site. Wu and colleagues36 found that asymmetry in the repair can also increase the strength and decrease gapping. Creating a repair in which the purchase of 2 separate modified Kessler stitches, one with a purchase length of 8 mm on one side and 12 mm on the other and the second stitch is a mirror image reversing the sides for the 8- and 12-mm purchase, created a construct that was shown to have decreased gapping at initial loading as well as after cyclical loading when compared with symmetric repairs with a purchase length of 10 or 12 mm from the laceration. Using an epitendinous suture increases the strength of the repair. Traditionally, either a 5-0 or 6-0 monofilament suture has been used. Several studies have shown that some form of cross-stitch or interlocking horizontal mattress decreases gliding resistance and increases the maximal strength of the repair construct.37 In an attempt to increase the strength of the repair and improve surgical times, fibrin glue has been used to augment the repair. A direct comparison was performed between repairs that were augmented with an epitendinous suture and repairs augmented with fibrin glue. The linear stiffness, force to produce a 2-mm gap, and ultimate failure were similar between the two groups, whereas the fibrin glue repair had an increased gliding resistance when compared with the epitendinous repair.38 Based on this information, an epitendinous suture adds strength, decreases gap formation, and improves the overall construct
created with the tendon repair and should be used whenever possible. Hwang and colleagues39 showed that repairing the FDP and both slips of the FDS increases the work of flexion by 51%, whereas repairing the FDP alone increased the work by 21%. Repairing only one slip of the FDS increased the work by an additional 9%. Because of this, one may feel comfortable with only repairing one slip of the FDS if it improves gliding of the flexor tendons through their flexor sheath without compromising the patients’ outcomes.
SUMMARY Flexor tendon healing is a complex collaboration between the tendons and their surrounding milieu. The goal is to increase the strength of the repair construct to allow for appropriate tendon healing while minimizing the scar formation to the surrounding tissues. By preserving the blood supply to the tendon through its vincula, we can maintain the nutrients needed for tendon healing. The first stage of tendon healing relies on an initial inflammatory response; with the possibility of increasing the effectiveness and decreasing the side effects of biological factors, such as TGF-b, NF-kb, and VEGF, we may be able to tilt the balance of tendon healing and adhesion formation in our favor. The use of simple and safe medications, such as NSAIDs, may also help with the battle between healing and scar. Using an appropriate construct when repairing an injured tendon aids in the ability to mobilize the digits, which also aids in decreasing adhesion formation. Using at least a 4-strand repair, of either a 3-0 or 4-0 suture with a purchase length of 7 to 12 mm, is necessary to allow for early active motion of the injured digits. By adding an epitendonous suture, we can both increase the strength of the repair as well as decrease the gliding resistance of the repair site. This construct allows for early passive motion while decreasing the chance of gap formation, which should allow for appropriate healing of the tendon while limiting the adhesion formation with the tendon sheath.
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38. Xu NM, Brown PJ, Plate JF, et al. Fibrin glue augmentation for flexor tendon repair increases friction compared with epitendinous suture. J Hand Surg Am 2013;38(12):2329–34. 39. Hwang MD, Pettrone S, Trumble TE. Work of flexion related to different suture materials after flexor digitorum profundus and flexor digitorum superficialis tendon repair in zone II: a biomechanical study. J Hand Surg Am 2009;34:700–4.