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Recent Progress in Flexor Tendon Healing
SCIENTIFIC/CLINICAL ARTICLES JHT Read for Credit Article #002
Recent Progress in Flexor Tendon Healing The Modulation of Tendon Healing with Rehabilitation Variables Martin I. Boyer, MD Charles A. Goldfarb, MD Richard H. Gelberman, MD Department of Orthopaedic Surgery Orthopaedic Hand Surgery Service Saint Louis, Missouri
BACKGROUND In the 1960s, the first reports demonstrated that flexor tendon lacerations within the confines of the fibro-osseous flexor digital sheath could be repaired primarily, and rehabilitation be carried out successfully, without excision of the lacerated tendons followed by primary tendon grafting.1,2 Major advances in the understanding of intrasynovial flexor tendon biology have been made since that time. The concept of adhesion-free tendon healing has been validated both in experimental and in clinical studies since that time,3–6 lending support to efforts which attempt to achieve a reliable technique of primary flexor tendon repair and digital rehabilitation without the inevitable need for later tenolysis because of ingrowth of restrictive adhesions from the surrounding sheath. Despite advances in the repair and rehabilitation of injured flexor tendons within the fibroosseous digital sheath, the results, measured experimentally as Correspondence and reprint requests to Martin I. Boyer, MD, MSc, FRCS (C), Department of Orthopaedic Surgery, Orthopaedic Hand Surgery Service, Suite 11300, West Pavilion, One Barnes Hospital Plaza, Saint Louis, MO 63110; e-mail:. doi:10.1197/j.jht.2005.01.009
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ABSTRACT: Until recently, attempts to optimize the postoperative regimen following intrasynovial flexor tendon repair had been essentially empirical, in that both the time and graduation of the exercise regimen have lacked clear conceptual guidelines. The magnitude of load applied in previous studies had not been clearly controlled, and similarly, the effects of increased repair site excursion and gap formation had not been evaluated in clinically relevant models. Recent experimental in vivo data on the application of force and excursion as independent variables by the authors and other investigators have helped to clarify the respective roles of these two variables. The goal of surgical treatment of intrasynovial flexor tendon lacerations is the achievement of a primary tendon repair of tensile strength sufficient to allow early controlled motion after surgery. The implementation of an appropriate postoperative rehabilitation protocol will, based on the experimental data discussed in this article, decrease the formation of intrasynovial adhesions, facilitate the restoration of the gliding surface, and stimulate the accrual of strength at the repair site. J HAND THER. 2005;18:80–85.
tendon excursion and clinically as digital range of motion, continue to be unpredictable. Historically, several factors contributing to the formation of adhesions (tendon suture, sheath injury, and postoperative immobilization) have been considered to be unavoidable components of the injury and the repair process.7 A number of scientific and prospective clinical studies have shown that it is possible to obtain adhesion-free (so-called primary) tendon healing with the timely application of protected passive motion rehabilitation.8–10 Duran et al.11,12 suggested that as little as 3 mm intrasynovial excursion is sufficient to prevent the formation of restrictive adhesions and the firm adherence of the repaired tendon within the digital sheath. Other investigators have also demonstrated both experimentally and clinically, that protected motion can effectively restore the tendon’s gliding surface, leading to improved repair site strength and excursion.13–17 There has been considerable concern, however, about whether the early application of motion postoperatively would invariably lead to repair site failure. In 1941, Mason and Allen18 described the site of an immature tendon repair as a gelatinous exudate between the two tendon stumps that, between five and nine days after repair, underwent
considerable softening and loss of tensile strength. In 1960, Lindsay et al.19 explored the causes of gap formation at the intrasynovial repair site in chickens. Inadequate immobilization was associated with increased adhesion formation and increased tendon callus size, and was thought to be a major cause of significant repair site elongation. Ketchum et al.20,21 observed that gaps as small as 1 mm were associated with increased formation of adhesions, and were detrimental to tendon function. Seradge22 concurred, demonstrating that the formation of repair site gaps correlated directly with poor clinical outcomes. To minimize the formation of repair site gaps, Lindsay et al. advocated increasing the length of immobilization—a concept supported clinically by Potenza, Peacock, and others.23–26 Invocations that the application of ‘‘excessive’’ stress to an immature repair site would lead to gap formation and poor clinical results created a formidable challenge for those seeking to improve the rehabilitation of these injuries. Realizing that the greater the rehabilitation force applied to the repair site, the greater the risk of gap formation and repair site failure, modern suture techniques that attempt to improve the time-zero (time of tendon repair) and early postoperative biomechanical characteristics of the repair site have been developed.27–32 These suture techniques demonstrate improved time-zero tensile properties, and have shown in experimental studies to minimize the formation of repair site gaps and adhesions. Ex vivo and in vivo investigations in linear, in situ, and other models have suggested that core suture configurations with the greatest tensile strength are those in which there are multiple sites of tendon suture interaction. Although the Kessler1,33 or modified Kessler techniques still enjoy widespread acceptance, newer techniques such as Tajima,34 Strickland,35–37 Cruciate,38 Becker,39 and Savage30 configurations all offer greater suture hold on the tendon that is independent of the suture knot. These modern methods of core suture technique have been shown to offer not only greater time-zero repair site tensile strength, but also improved strength up to and including six weeks postoperatively.28 Although substantial advances had been made in core suture technique, attempts to optimize the postoperative regimen following intrasynovial flexor tendon repair had been essentially empirical, in that both the time and graduation of the exercise regimen have lacked clear conceptual guidelines. The magnitude of load applied in previous studies had not been clearly controlled, and similarly, the effects of increased repair site excursion and gap formation have not been evaluated in clinically relevant models. The goal of the surgical treatment of intrasynovial flexor tendon lacerations is the achievement of a primary tendon repair of tensile strength sufficient
to allow the application of a postoperative motion rehabilitation protocol to inhibit the formation of intrasynovial adhesions, facilitate restoration of the gliding surface, and stimulate the accrual of strength at the repair site.
SCIENTIFIC AND CLINICAL BASIS FOR APPLICATION OF FORCE Over the past 50 years, details about the response of fibroblasts to mechanical load have been provided.15,40–44 Becker et al.45 applied static loads to chicken tendons in vitro and noted increased fibroblast migration, increased collagen deposition, and improved alignment of cells along the axis of applied tension compared to unloaded controls. Slack et al.43 cultured digital flexor tendons on an apparatus designed to apply controlled mechanical loads. They noted an increase in synthetic capability, with higher levels of DNA, protein, and glycosaminoglycans in tendons loaded for 48 to 72 hours. Almekinders et al.46 designed an in vitro model to study the effects of repetitive motion on human fibroblasts. Cells that underwent cyclic deformation showed significantly increased levels of prostaglandin E2 production. Mass et al.42 studied the effects of constant mechanical load on rabbit flexor tendon in vitro. The tendons showed increased strength by three weeks (during scar maturation), confirming the ability to heal through intrinsic mechanisms independent of adhesion formation. Importantly, the investigators noted greater extensibility in unloaded tendons and surmised that the effect resulted from a more random orientation of collagen fibers in those tendons producing a deformable meshwork. The concept that an increase in stress alone, without a significant increase in tendon excursion, improves the quality of the repair response and decreases adhesion formation has been addressed in several clinically relevant experimental studies. Hitchcock et al.,17 focusing on the loss of repair site tensile strength (‘‘softening’’) seen characteristically in the first postoperative week, studied the effects of immediate constrained digital motion on the strength of flexor tendon repairs in chickens. They found that early controlled motion diminished profoundly the adhesion response and obviated the softening of tendon seen frequently with postoperative immobilization. Tendons of the mobilized digits showed early and progressive strength gains. Strickland and Glogovac,15 in a clinical study, demonstrated that digits mobilized with early passive motion demonstrated an increased total active motion compared to nonmobilized digits. Specifically, the percentage of good results improved by over 40% with the utilization of early controlled passive motion compared to immobilization. Feehan and Beauchene47 April–June 2005
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demonstrated a significant increase in repair site stiffness and ultimate stress in tendons that were mobilized compared to their immobilized counterparts. Taken together, these experimental and clinical studies lent support to the concept that stress applied to the repair site in the immediate postoperative period markedly improved healing efficiency. Although the clinical and experimental results seen with the application of low levels of postoperative force were promising, some authors advocated increasing the levels in vivo applied force during rehabilitation. In a clinical study, Small et al.48 reported 77% good and excellent results in a series of 98 patients treated with controlled active motion rehabilitation. The investigators noted that the necessity of secondary reconstructive procedures such as tenolysis decreased by 75% with the use of an active motion program. They did, however, report a rupture rate of 9%. This high level of repair site failure is cautionary, because loads applied to the repair site with active motion rehabilitation protocols may lack suitable control and therefore may exceed the repair site’s ultimate load capacity during the first postoperative weeks. In an effort to define the in vivo forces seen clinically during passive and active range of motion activities, Schuind et al.49 applied buckle transducers to the flexor tendons of patients undergoing open carpal tunnel surgery. They found a large variation in the in vivo force from between 1 N and 34 N for passive single digit flexion and active tip pinch. Mean values for passive digital flexion were approximately 3 to 5 N, whereas values for passive digital flexion with extension were between 15 to 20 N. Lieber et al.50,51 demonstrated subsequently in a canine model that significant differences in intrasynovial tendon gliding and in vivo tendon force could be demonstrated by applying rehabilitation regimens differing in the extent of applied digital and wrist flexion and extension movements. The smallest amounts of intrasynovial flexor tendon excursion and the lowest levels of applied in vivo force occurred with passive digital flexion-extension carries out with the wrist held in flexion. Mean loads of less than 5 N and excursions of 1.7 mm were achieved on the canine flexor digitorum profundus tendon. Passive digital flexion and extension with the wrist held in extension increased significantly both the levels of force (average 17 N) and the levels of intrasynovial excursion (3.5 mm). Passive digital flexion and extension with synergistic wrist extension and flexion likewise increased tendon excursion, but minimized applied load. By application of these rehabilitation regimens, it has been possible to isolate both repair site excursion and applied musculotendinous load as independent variables in the investigation of their individual effects in a clinically relevant model of flexor tendon rehabilitation whose 82
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measured values of force and excursion replicate directly those achieved during rehabilitation in humans. The importance of these three studies cannot be overstated.
SCIENTIFIC AND CLINICAL BASIS FOR THE APPLICATION OF EXCURSION In recent experimental trials, clinical investigators have focused on increasing the magnitude of tendon excursion in contrast to in vivo force.16,17,52–55 In an effort to increase the magnitude of tendon excursion and reduce in vivo force clinically, Silfverskiold et al.56 recommended a modification of the technique in which digits are mobilized. They believed that a tethering effect occurred when digits were flexed and extended individually, and recommended that four-finger flexion rehabilitation be used to achieve increased intrasynovial repair site excursion. The investigators posited that an increase in excursion of between 6 to 9 mm constituted the threshold needed to demonstrate benefit. Horii et al.16 used synergistic wrist motion to eliminate the tendons’ slackness in the palm, in an effort to increase excursion without increasing applied load. Without applied load, excursions of 5 mm were seen. With applied loads of 3 or 4 N, intrasynovial excursion of up to 13 mm were seen. When two traditional splints were compared to a splint allowing synergistic wrist motion, the authors noted several remarkable benefits: tendon crimping was reduced, excursion was increased and buckling under the pulley system was obviated. The conclusion was, however, that increased force application was required for the benefits of synergistic motion to be realized. In a clinical study, Hagberg and Selvik53 demonstrated that methods of rehabilitation utilizing increased levels of both force and excursion (realized by combining passive digital flexion with synergistic wrist motion, along with active digital contraction) resulted in improved repair site excursion. However, considerable repair site elongation as measured by intratendinous metallic markers was seen. Investigators have, in the past, believed that repair site elongation ( gap formation) and the formation of intrasynovial restrictive adhesions were related directly. In a study using a clinically relevant canine model, it was convincingly demonstrated that repair site gap formation during the first six postoperative weeks does not correlate with loss of digital motion or with the formation of intrasynovial adhesions.57 The effect of gap formation seen during the first three postoperative weeks was only to obviate the time dependent accrual of repair site strength seen between three and six weeks postoperatively if the size of the gap exceeded 3 mm in length.
THE EFFECT OF PROXIMAL MUSCULOTENDINOUS FORCE AND INTRASYNOVIAL REPAIR SITE EXCURSION, AS INDEPENDENT VARIABLES, ON REPAIR SITE STRUCTURE AND FUNCTION Previous investigations have demonstrated that the repair site during the early postoperative period is active in the synthesis of compounds known to be responsible for the transduction of extracellular matrix signals to the interior of the fibroblast, and for compounds stimulating angiogenesis directly.58–61 In addition, tendon cells and explants respond positively to applied mechanical stress.40–44 On the basis of these studies, we hypothesized that intrasynovial flexor tendons treated with protected passive motion would be responsive to variations in applied in vivo force during the first six weeks after repair. Two-hundred and fourteen canine intrasynovial flexor tendon repairs were assigned to one of four groups based on the rehabilitation method (low force [,5 N] or high force [17 N]) and the repair technique ( four-strand or eight-strand core suture). Animals were killed at intervals between five and 42 days postoperatively. Repair site structural properties were determined by tensile testing, and digital range of motion was assessed by a motion analysis system. We found that the tensile properties did not differ between the low- and the high-force rehabilitation groups, irrespective of repair technique.62 By contrast, the tensile properties were affected significantly by the repair technique with the tendons in the eightstrand group having a significantly higher ultimate force than those in the four-strand group throughout the postoperative period. As demonstrated in a previously published study, ultimate force did not change significantly with time during the first 21 days.57 Of note, there was no evidence of tendon softening in either of the rehabilitation groups. The repair site ultimate strength increased significantly from 21 to 42 days in all groups. This study demonstrated that increasing the level of clinically relevant applied musculotendinous force from 5 to 17 N during the immediate postoperative period did not accelerate the timedependent accrual of repair site strength or stiffness. Suture technique was of primary importance, however, in providing a strong and stiff repair site throughout the early healing interval. These findings suggested that there be a re-evaluation of the concept that increases in force provided by more vigorous rehabilitation techniques are beneficial to early tendon healing. Even in the context of modern eight-strand suture repair techniques, increased applied force might potentially increase the incidence of repair site dehiscence or gap formation, and is not advocated at present.
The effects of increased in vivo tendon excursion (independent of applied musculotendinous force) on digital range of motion and tendon strength after flexor digitorum profundus (FDP) tendon transection and repair were evaluated as well.63 Ninety-six FDP tendons were injured, repaired and treated by lowforce (5 N) passive mobilization rehabilitation protocols starting on the first postoperative day. The protocols held the applied force constant but varied the excursion achieved: 1.7 mm of intrasynovial excursion for the low-excursion group, and 3.5 mm for the high-excursion group. Rehabilitation for the first group (low force/low excursion) consisted of passive flexion and extension of the four digits with the wrist maintained in the flexed position; for the second group (low force/high excursion) the wrist and digits flexed and extended simultaneously. Our results indicated that the use of rehabilitation that produced increased tendon excursion within the context of low applied force did not influence range-of-motion or tensile properties. Joint rotation and tendon excursion in digits from the low-force/ low-excursion and low-force/high-excursion groups were not significantly different ( p > 0.05), with both groups not significantly different from unoperated controls. Tensile structural properties (ultimate force, rigidity, strain at 20 N, strain at failure) were not significantly affected by increased excursion ( p > 0.05). We conclude that a threshold of 1.7 mm of tendon excursion is sufficient to inhibit adhesion formation and to allow excellent recovery of functional properties following sharp transection of the canine FDP tendon. Additional excursion, at the same low force level, appeared to provide little added benefit. These results contrast those recently reported by Zhao et al.,64 who demonstrated in an in vivo canine model of partial tendon laceration and repair that, based on improvements in adhesion breaking strength and decreased overall formation of adhesions, synergistic wrist motion coupled with passive digital flexion was beneficial to tendon healing and digital motion. Although the model utilized was one of partial tendon laceration and repair wherein the force required to rupture the repair site averaged a minimum of 135 N (over seven times that force applied during clinically relevant high-force rehabilitation), the implication is that increased tendon excursion within the context of low applied force may be of benefit in the minimization of the formation of intrasynovial adhesions.
SUMMARY Based on presently available experimental and clinical data, we conclude that primary repair of a intrasynovial flexor tendon laceration65 using a modern multistrand core and epitendinous suture April–June 2005
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technique27 should be able to withstand repair site gap formation of 3 mm during the first three postoperative weeks.57 A passive motion rehabilitation protocol that strives to emphasize intrasynovial repair site excursion,63 rather than increased application of musculotendinous force62 across the repair site, should be utilized.66 We currently perform an eight-strand, locked repair using a synthetic, coated suture supplemented by an epitendinous running repair within ten to 14 days of injury. Therapy begins on postoperative day 1 with a synergistic protocol. Early motion is protected by a hinged splint, with wrist extension typically blocked at 30 degrees and MP extension typically blocked at 70 degrees. Early place and hold is also utilized. Close coordination between the therapist and surgeon helps to maximize outcome by modifying the rehabilitation protocol for the individual patient as necessary.
REFERENCES 1. Kessler I, Nissim F. Primary repair without immobilization of flexor tendon division within the digital sheath. An experimental and clinical study. Acta Orthop Scand. 1969;40:587–601. 2. Verdan C. Primary repair of flexor tendons. J Bone Joint Surg Am. 1960;42:647–57. 3. Gelberman RH, Manske PR, Akeson WH, Woo SL, Lundborg G, Amiel D. Flexor tendon repair. J Orthop Res. 1986;4:119–28. 4. Lundborg G. Experimental flexor tendon healing without adhesion formation—a new concept of tendon nutrition and intrinsic healing mechanisms. A preliminary report. Hand. 1976;8:235–8. 5. Lundborg G, Rank F. Experimental intrinsic healing of flexor tendons based upon synovial fluid nutrition. J Hand Surg [Am]. 1978;3:21–31. 6. Lundborg G, Rank F. Tendon healing: intrinsic mechanisms. In: Hunter J, Schneider L, Mackin E (eds). Tendon Surgery in the Hand. St. Louis: CV Mosby, 1987, pp 54–60. 7. Matthews P, Richards H. Factors in the adherence of flexor tendon after repair: an experimental study in the rabbit. J Bone Joint Surg Br. 1976;56:618–25. 8. Gelberman RH, Amifl D, Gonsalves M, Woo S, Akeson WH. The influence of protected passive mobilization on the healing of flexor tendons: a biochemical and microangiographic study. Hand. 1981;13:120–8. 9. Gelberman RH, Woo SL, Lothringer K, Akeson WH, Amiel D. Effects of early intermittent passive mobilization on healing canine flexor tendons. J Hand Surg [Am]. 1982;7:170–5. 10. Woo SL, Gelberman RH, Cobb NG, Amiel D, Lothringer K, Akeson WH. The importance of controlled passive mobilization on flexor tendon healing. A biomechanical study. Acta Orthop Scand. 1981;52:615–22. 11. Duran R, Houser R, Coleman C, Postlewaite D. A preliminary report in the use of controlled passive motion following flexor tendon repair in zones II and III (abstract). J Hand Surg. 1976; 1:79. 12. Duran RJ, Houser RG. Controlled passive motion following flexor tendon repair in zones 2 and 3. In: AAOS Symposium on Tendon Surgery in the Hand. St. Louis: CV Mosby, 1975, pp 105–14. 13. Lister GD, Kleinert HE, Kutz JE, Atasoy E. Primary flexor tendon repair followed by immediate controlled mobilization. J Hand Surg [Am]. 1977;2:441–51. 14. Kleinert HE, Kutz JE, Atasoy E, Stormo A. Primary repair of flexor tendons. Orthop Clin North Am. 1973;4:865–76.
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15. Strickland JW, Glogovac SV. Digital function following flexor tendon repair in Zone II: A comparison of immobilization and controlled passive motion techniques. J Hand Surg [Am]. 1980; 5:537–43. 16. Horii E, Lin GT, Cooney WP, Linscheid RL, An KN. Comparative flexor tendon excursion after passive mobilization: an in vitro study. J Hand Surg [Am]. 1992;17:559–66. 17. Hitchcock TF, Light TR, Bunch WH, et al. The effect of immediate constrained digital motion on the strength of flexor tendon repairs in chickens. J Hand Surg [Am]. 1987;12: 590–5. 18. Mason ML, Allen HS. The rate of healing of tendons: an experimental study of tensile strength. Ann Surg. 1941;113: 424–59. 19. Lindsay W, Thompson H, Walker H. Digital flexor tendons: an experimental study. Br J Plast Surg. 1960;13:1–9. 20. Ketchum LD. Primary tendon healing: a review. J Hand Surg. 1977;2:428–35. 21. Ketchum LD, Martin NL, Kappel DA. Experimental evaluation of factors affecting the strength of tendon repairs. Plast Reconstr Surg. 1977;59:708–19. 22. Seradge H. Elongation of the repair configuration following flexor tendon repair. J Hand Surg [Am]. 1983;8:182–5. 23. Potenza A. Concepts of tendon healing and repair. In: AAOS Symposium on Tendon Surgery in the Hand. St. Louis: CV Mosby, 1975, pp 18–47. 24. Potenza A. Philosophy of flexor tendon surgery. Orthop Clin North Am. 1986;17:349–52. 25. Peacock E. Fundamental aspect of wound healing relating to the restoration of gliding function after tendon repair. Surg Gynecol Obstet. 1964;119:241–50. 26. Peacock E. Biological principles in the healing of long tendons. Surg Clin North Am. 1965;45:461–76. 27. Winters SC, Gelberman RH, Woo SL-Y, Chan SS, Grewal R, Seiler JG. The effects of multiple-strand suture methods on the strength and excursion of repaired intrasynovial flexor tendon: a biomechanical study in dogs. J Hand Surg [Am]. 1998;23: 97–104. 28. Winters SC, Seiler JG III, Woo SL, Gelberman RH. Suture methods for flexor tendon repair. A biomechanical analysis during the first six weeks following repair. Ann Chir Main Memb Super. 1997;16:229–34. 29. Taras J, Skahen J, James R, Raphael J, Marzyk S, Bauerle W. The double-grasping and cross-stitch for acute flexor tendon repair: Applications with active motion. Atlas Hand Clin. 1996;1:13–28. 30. Savage R. In vitro studies of a new method of flexor tendon repair. J Hand Surg [Br]. 1985;10:135–41. 31. Lin GT, An KN, Amadio PC. Cooney WP III. Biomechanical studies of running suture for flexor tendon repair in dogs. J Hand Surg [Am]. 1988;13:553–8. 32. Wagner WF Jr, Carroll Ct, Strickland JW, Heck DA, Toombs JP. A biomechanical comparison of techniques of flexor tendon repair. J Hand Surg [Am]. 1994;19:979–83. 33. Kessler I. The ‘‘grasping’’ technique for tendon repair. Hand. 1973;5:253–5. 34. Tajima T. History, current status, and aspects of hand surgery in Japan. Clin Orthop. 1984;184:41–9. 35. Strickland JW. Flexor tendon repair. Hand Clin. 1985;1:55–68. 36. Strickland J. Flexor tendon repair: Indiana method. Indiana Hand Center Newsletter. 1993;1:1–12. 37. Strickland JW. Flexor tendon injuries: II. Operative technique. J Am Acad Orthop Surg. 1995;3:55–62. 38. McLarney E, Hoffman H, Wolfe SW. Biomechanical analysis of the cruciate four-strand flexor tendon repair. J Hand Surg [Am]. 1999;24:295–301. 39. Becker H. Primary repair of flexor tendons in the hand without immobilization: preliminary report. Hand. 1978;10:37–47. 40. Harris E, Bass B, Walker L. Tensile strength and stress-strain relationships in cadaveric human tendons [abstract]. Anat Rec. 1964;148:289. 41. Gillard GC, Reilly HC, Bell-Booth PG, Flint MH. The influence of mechanical forces on the glycosaminoglycan content of the
42.
43.
44.
45.
46.
47.
48.
49.
50.
51.
52. 53.
54.
55.
rabbit flexor digitorum profundus tendon. Connect Tissue Res. 1979;7:37–46. Mass DP, Tuel RJ, Labarbera M, Greenwald DP. Effects of constant mechanical tension on the healing of rabbit flexor tendons. Clin Orthop. 1993;296:301–6. Slack CM, Flint MH, Thompson BM. The effect of tensional load on isolated embryonic chick tendons in organ culture. Connect Tissue Res. 1984;12:229–47. Woo SL, Gomez MA, Amiel D, Ritter MA, Gelberman RH, Akeson WH. The effects of exercise on the biomechanical and biochemical properties of swine digital flexor tendons. J Biomech Eng. 1981;103:51–6. Becker H, Graham MF, Cohen IK, Diegelmann RF. Intrinsic tendon cell proliferation in tissue culture. J Hand Surg [Am]. 1981;6:616–9. Almekinders L, Banes A, Ballenger C. Effects of repetitive motion on human fibroblasts. Med Sci Sports Exer. 1993;25: 603–7. Feehan LM, Beauchene JG. Early tensile properties of healing chicken flexor tendons: early controlled passive motion versus postoperative immobilization. J Hand Surg [Am]. 1990;15:63–8. Small JO, Brennen MD, Colville J. Early active mobilisation following flexor tendon repair in zone 2. J Hand Surg [Br]. 1989;14:383–91. Schuind F, Garcia-Elias M, Cooney WP III, An KN. Flexor tendon forces: in vivo measurements. J Hand Surg [Am]. 1992; 17:291–8. Lieber RL, Amiel D, Kaufman KR, Whitney J, Gelberman RH. Relationship between joint motion and flexor tendon force in the canine forelimb. J Hand Surg [Am]. 1996;21:957–62. Lieber RL, Silva MJ, Amiel D, Gelberman RH. Wrist and digital joint motion produce unique flexor tendon force and excursion in the canine forelimb. J Biomech. 1999;32:175–81. Cannon NM, Strickland JW. Therapy following flexor tendon surgery. Hand Clin. 1985;1:147–65. Hagberg L, Selvik G. Tendon excursion and dehiscence during early controlled mobilization after flexor tendon repair in zone II: an x-ray stereophotogrammetric analysis. J Hand Surg [Am]. 1991;16:669–80. Horibe S, Woo SL, Spiegelman JJ, Marcin JP, Gelberman RH. Excursion of the flexor digitorum profundus tendon: a kinematic study of the human and canine digits. J Orthop Res. 1990; 8:167–74. May EJ, Silfverskiold KL. Rate of recovery after flexor tendon repair in zone II. A prospective longitudinal study of 145 digits. Scand J Plast Reconstr Surg Hand Surg. 1993;27:89–94.
56. Silfverskiold KL, May EJ, Tornvall AH. Gap formation during controlled motion after flexor tendon repair in zone II: a prospective clinical study. J Hand Surg [Am]. 1992;17: 539–46. 57. Gelberman RH, Boyer MI, Brodt MD, Winters SC, Silva MJ. The effect of gap formation at the repair site on the strength and excursion of intrasynovial flexor tendons. An experimental study on the early stages of tendon-healing in dogs. J Bone Joint Surg Am. 1999;81:975–82. 58. Harwood FL, Goomer RS, Gelberman RH, Silva MJ, Amiel D. Regulation of alpha(v)beta3 and alpha5beta1 integrin receptors by basic fibroblast growth factor and platelet-derived growth factor-BB in intrasynovial flexor tendon cells. Wound Repair Regen. 1999;7:381–8. 59. Harwood FL, Monosov AZ, Goomer RS, et al. Integrin expression is upregulated during early healing in a canine intrasynovial flexor tendon repair and controlled passive motion model. Connect Tissue Res. 1998;39:309–16. 60. Boyer MI, Watson JT, Lou J, Manske PR, Gelberman RH, Cai SR. Quantitative variation in vascular endothelial growth factor mRNA expression during early flexor tendon healing: an investigation in a canine model. J Orthop Res. 2001;19: 869–72. 61. Bidder M, Towler DA, Gelberman RH, Boyer MI. Expression of mRNA for vascular endothelial growth factor at the repair site of healing canine flexor tendon. J Orthop Res. 2000;18: 247–52. 62. Boyer MI, Gelberman RH, Burns ME, Dinopoulos H, Hofem R, Silva MJ. Intrasynovial flexor tendon repair. An experimental study comparing low and high levels of in vivo force during rehabilitation in canines. J Bone Joint Surg Am. 2001;83:891–9. 63. Silva MJ, Brodt MD, Boyer MI, et al. Effects of increased in vivo excursion on digital range of motion and tendon strength following flexor tendon repair. J Orthop Res. 1999;17:777–83. 64. Zhao C, Amadio PC, Momose T, Couvreur P, Zobitz ME, An KN. Effect of synergistic wrist motion on adhesion formation after repair of partial flexor digitorum profundus tendon lacerations in a canine model in vivo. J Bone Joint Surg Am. 2002;84:78–84. 65. Gelberman RH, Siegel DB, Woo SL, Amiel D, Takai S, Lee D. Healing of digital flexor tendons: importance of the interval from injury to repair. A biomechanical, biochemical, and morphological study in dogs. J Bone Joint Surg Am. 1991;73: 66–75. 66. Silva MJ, Boyer MI, Gelberman RH. Recent progress in flexor tendon healing. J Orthop Sci. 2002;7:508–14.
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Recent Progress in Flexor Tendon Healing The Modulation of Tendon Healing with Rehabilitation Variables Martin I. Boyer, MD Charles A. Goldfarb, MD Richard H. Gelberman, MD Department of Orthopaedic Surgery Orthopaedic Hand Surgery Service Saint Louis, Missouri
BACKGROUND In the 1960s, the first reports demonstrated that flexor tendon lacerations within the confines of the fibro-osseous flexor digital sheath could be repaired primarily, and rehabilitation be carried out successfully, without excision of the lacerated tendons followed by primary tendon grafting.1,2 Major advances in the understanding of intrasynovial flexor tendon biology have been made since that time. The concept of adhesion-free tendon healing has been validated both in experimental and in clinical studies since that time,3–6 lending support to efforts which attempt to achieve a reliable technique of primary flexor tendon repair and digital rehabilitation without the inevitable need for later tenolysis because of ingrowth of restrictive adhesions from the surrounding sheath. Despite advances in the repair and rehabilitation of injured flexor tendons within the fibroosseous digital sheath, the results, measured experimentally as Correspondence and reprint requests to Martin I. Boyer, MD, MSc, FRCS (C), Department of Orthopaedic Surgery, Orthopaedic Hand Surgery Service, Suite 11300, West Pavilion, One Barnes Hospital Plaza, Saint Louis, MO 63110; e-mail:
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ABSTRACT: Until recently, attempts to optimize the postoperative regimen following intrasynovial flexor tendon repair had been essentially empirical, in that both the time and graduation of the exercise regimen have lacked clear conceptual guidelines. The magnitude of load applied in previous studies had not been clearly controlled, and similarly, the effects of increased repair site excursion and gap formation had not been evaluated in clinically relevant models. Recent experimental in vivo data on the application of force and excursion as independent variables by the authors and other investigators have helped to clarify the respective roles of these two variables. The goal of surgical treatment of intrasynovial flexor tendon lacerations is the achievement of a primary tendon repair of tensile strength sufficient to allow early controlled motion after surgery. The implementation of an appropriate postoperative rehabilitation protocol will, based on the experimental data discussed in this article, decrease the formation of intrasynovial adhesions, facilitate the restoration of the gliding surface, and stimulate the accrual of strength at the repair site. J HAND THER. 2005;18:80–85.
tendon excursion and clinically as digital range of motion, continue to be unpredictable. Historically, several factors contributing to the formation of adhesions (tendon suture, sheath injury, and postoperative immobilization) have been considered to be unavoidable components of the injury and the repair process.7 A number of scientific and prospective clinical studies have shown that it is possible to obtain adhesion-free (so-called primary) tendon healing with the timely application of protected passive motion rehabilitation.8–10 Duran et al.11,12 suggested that as little as 3 mm intrasynovial excursion is sufficient to prevent the formation of restrictive adhesions and the firm adherence of the repaired tendon within the digital sheath. Other investigators have also demonstrated both experimentally and clinically, that protected motion can effectively restore the tendon’s gliding surface, leading to improved repair site strength and excursion.13–17 There has been considerable concern, however, about whether the early application of motion postoperatively would invariably lead to repair site failure. In 1941, Mason and Allen18 described the site of an immature tendon repair as a gelatinous exudate between the two tendon stumps that, between five and nine days after repair, underwent
considerable softening and loss of tensile strength. In 1960, Lindsay et al.19 explored the causes of gap formation at the intrasynovial repair site in chickens. Inadequate immobilization was associated with increased adhesion formation and increased tendon callus size, and was thought to be a major cause of significant repair site elongation. Ketchum et al.20,21 observed that gaps as small as 1 mm were associated with increased formation of adhesions, and were detrimental to tendon function. Seradge22 concurred, demonstrating that the formation of repair site gaps correlated directly with poor clinical outcomes. To minimize the formation of repair site gaps, Lindsay et al. advocated increasing the length of immobilization—a concept supported clinically by Potenza, Peacock, and others.23–26 Invocations that the application of ‘‘excessive’’ stress to an immature repair site would lead to gap formation and poor clinical results created a formidable challenge for those seeking to improve the rehabilitation of these injuries. Realizing that the greater the rehabilitation force applied to the repair site, the greater the risk of gap formation and repair site failure, modern suture techniques that attempt to improve the time-zero (time of tendon repair) and early postoperative biomechanical characteristics of the repair site have been developed.27–32 These suture techniques demonstrate improved time-zero tensile properties, and have shown in experimental studies to minimize the formation of repair site gaps and adhesions. Ex vivo and in vivo investigations in linear, in situ, and other models have suggested that core suture configurations with the greatest tensile strength are those in which there are multiple sites of tendon suture interaction. Although the Kessler1,33 or modified Kessler techniques still enjoy widespread acceptance, newer techniques such as Tajima,34 Strickland,35–37 Cruciate,38 Becker,39 and Savage30 configurations all offer greater suture hold on the tendon that is independent of the suture knot. These modern methods of core suture technique have been shown to offer not only greater time-zero repair site tensile strength, but also improved strength up to and including six weeks postoperatively.28 Although substantial advances had been made in core suture technique, attempts to optimize the postoperative regimen following intrasynovial flexor tendon repair had been essentially empirical, in that both the time and graduation of the exercise regimen have lacked clear conceptual guidelines. The magnitude of load applied in previous studies had not been clearly controlled, and similarly, the effects of increased repair site excursion and gap formation have not been evaluated in clinically relevant models. The goal of the surgical treatment of intrasynovial flexor tendon lacerations is the achievement of a primary tendon repair of tensile strength sufficient
to allow the application of a postoperative motion rehabilitation protocol to inhibit the formation of intrasynovial adhesions, facilitate restoration of the gliding surface, and stimulate the accrual of strength at the repair site.
SCIENTIFIC AND CLINICAL BASIS FOR APPLICATION OF FORCE Over the past 50 years, details about the response of fibroblasts to mechanical load have been provided.15,40–44 Becker et al.45 applied static loads to chicken tendons in vitro and noted increased fibroblast migration, increased collagen deposition, and improved alignment of cells along the axis of applied tension compared to unloaded controls. Slack et al.43 cultured digital flexor tendons on an apparatus designed to apply controlled mechanical loads. They noted an increase in synthetic capability, with higher levels of DNA, protein, and glycosaminoglycans in tendons loaded for 48 to 72 hours. Almekinders et al.46 designed an in vitro model to study the effects of repetitive motion on human fibroblasts. Cells that underwent cyclic deformation showed significantly increased levels of prostaglandin E2 production. Mass et al.42 studied the effects of constant mechanical load on rabbit flexor tendon in vitro. The tendons showed increased strength by three weeks (during scar maturation), confirming the ability to heal through intrinsic mechanisms independent of adhesion formation. Importantly, the investigators noted greater extensibility in unloaded tendons and surmised that the effect resulted from a more random orientation of collagen fibers in those tendons producing a deformable meshwork. The concept that an increase in stress alone, without a significant increase in tendon excursion, improves the quality of the repair response and decreases adhesion formation has been addressed in several clinically relevant experimental studies. Hitchcock et al.,17 focusing on the loss of repair site tensile strength (‘‘softening’’) seen characteristically in the first postoperative week, studied the effects of immediate constrained digital motion on the strength of flexor tendon repairs in chickens. They found that early controlled motion diminished profoundly the adhesion response and obviated the softening of tendon seen frequently with postoperative immobilization. Tendons of the mobilized digits showed early and progressive strength gains. Strickland and Glogovac,15 in a clinical study, demonstrated that digits mobilized with early passive motion demonstrated an increased total active motion compared to nonmobilized digits. Specifically, the percentage of good results improved by over 40% with the utilization of early controlled passive motion compared to immobilization. Feehan and Beauchene47 April–June 2005
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demonstrated a significant increase in repair site stiffness and ultimate stress in tendons that were mobilized compared to their immobilized counterparts. Taken together, these experimental and clinical studies lent support to the concept that stress applied to the repair site in the immediate postoperative period markedly improved healing efficiency. Although the clinical and experimental results seen with the application of low levels of postoperative force were promising, some authors advocated increasing the levels in vivo applied force during rehabilitation. In a clinical study, Small et al.48 reported 77% good and excellent results in a series of 98 patients treated with controlled active motion rehabilitation. The investigators noted that the necessity of secondary reconstructive procedures such as tenolysis decreased by 75% with the use of an active motion program. They did, however, report a rupture rate of 9%. This high level of repair site failure is cautionary, because loads applied to the repair site with active motion rehabilitation protocols may lack suitable control and therefore may exceed the repair site’s ultimate load capacity during the first postoperative weeks. In an effort to define the in vivo forces seen clinically during passive and active range of motion activities, Schuind et al.49 applied buckle transducers to the flexor tendons of patients undergoing open carpal tunnel surgery. They found a large variation in the in vivo force from between 1 N and 34 N for passive single digit flexion and active tip pinch. Mean values for passive digital flexion were approximately 3 to 5 N, whereas values for passive digital flexion with extension were between 15 to 20 N. Lieber et al.50,51 demonstrated subsequently in a canine model that significant differences in intrasynovial tendon gliding and in vivo tendon force could be demonstrated by applying rehabilitation regimens differing in the extent of applied digital and wrist flexion and extension movements. The smallest amounts of intrasynovial flexor tendon excursion and the lowest levels of applied in vivo force occurred with passive digital flexion-extension carries out with the wrist held in flexion. Mean loads of less than 5 N and excursions of 1.7 mm were achieved on the canine flexor digitorum profundus tendon. Passive digital flexion and extension with the wrist held in extension increased significantly both the levels of force (average 17 N) and the levels of intrasynovial excursion (3.5 mm). Passive digital flexion and extension with synergistic wrist extension and flexion likewise increased tendon excursion, but minimized applied load. By application of these rehabilitation regimens, it has been possible to isolate both repair site excursion and applied musculotendinous load as independent variables in the investigation of their individual effects in a clinically relevant model of flexor tendon rehabilitation whose 82
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measured values of force and excursion replicate directly those achieved during rehabilitation in humans. The importance of these three studies cannot be overstated.
SCIENTIFIC AND CLINICAL BASIS FOR THE APPLICATION OF EXCURSION In recent experimental trials, clinical investigators have focused on increasing the magnitude of tendon excursion in contrast to in vivo force.16,17,52–55 In an effort to increase the magnitude of tendon excursion and reduce in vivo force clinically, Silfverskiold et al.56 recommended a modification of the technique in which digits are mobilized. They believed that a tethering effect occurred when digits were flexed and extended individually, and recommended that four-finger flexion rehabilitation be used to achieve increased intrasynovial repair site excursion. The investigators posited that an increase in excursion of between 6 to 9 mm constituted the threshold needed to demonstrate benefit. Horii et al.16 used synergistic wrist motion to eliminate the tendons’ slackness in the palm, in an effort to increase excursion without increasing applied load. Without applied load, excursions of 5 mm were seen. With applied loads of 3 or 4 N, intrasynovial excursion of up to 13 mm were seen. When two traditional splints were compared to a splint allowing synergistic wrist motion, the authors noted several remarkable benefits: tendon crimping was reduced, excursion was increased and buckling under the pulley system was obviated. The conclusion was, however, that increased force application was required for the benefits of synergistic motion to be realized. In a clinical study, Hagberg and Selvik53 demonstrated that methods of rehabilitation utilizing increased levels of both force and excursion (realized by combining passive digital flexion with synergistic wrist motion, along with active digital contraction) resulted in improved repair site excursion. However, considerable repair site elongation as measured by intratendinous metallic markers was seen. Investigators have, in the past, believed that repair site elongation ( gap formation) and the formation of intrasynovial restrictive adhesions were related directly. In a study using a clinically relevant canine model, it was convincingly demonstrated that repair site gap formation during the first six postoperative weeks does not correlate with loss of digital motion or with the formation of intrasynovial adhesions.57 The effect of gap formation seen during the first three postoperative weeks was only to obviate the time dependent accrual of repair site strength seen between three and six weeks postoperatively if the size of the gap exceeded 3 mm in length.
THE EFFECT OF PROXIMAL MUSCULOTENDINOUS FORCE AND INTRASYNOVIAL REPAIR SITE EXCURSION, AS INDEPENDENT VARIABLES, ON REPAIR SITE STRUCTURE AND FUNCTION Previous investigations have demonstrated that the repair site during the early postoperative period is active in the synthesis of compounds known to be responsible for the transduction of extracellular matrix signals to the interior of the fibroblast, and for compounds stimulating angiogenesis directly.58–61 In addition, tendon cells and explants respond positively to applied mechanical stress.40–44 On the basis of these studies, we hypothesized that intrasynovial flexor tendons treated with protected passive motion would be responsive to variations in applied in vivo force during the first six weeks after repair. Two-hundred and fourteen canine intrasynovial flexor tendon repairs were assigned to one of four groups based on the rehabilitation method (low force [,5 N] or high force [17 N]) and the repair technique ( four-strand or eight-strand core suture). Animals were killed at intervals between five and 42 days postoperatively. Repair site structural properties were determined by tensile testing, and digital range of motion was assessed by a motion analysis system. We found that the tensile properties did not differ between the low- and the high-force rehabilitation groups, irrespective of repair technique.62 By contrast, the tensile properties were affected significantly by the repair technique with the tendons in the eightstrand group having a significantly higher ultimate force than those in the four-strand group throughout the postoperative period. As demonstrated in a previously published study, ultimate force did not change significantly with time during the first 21 days.57 Of note, there was no evidence of tendon softening in either of the rehabilitation groups. The repair site ultimate strength increased significantly from 21 to 42 days in all groups. This study demonstrated that increasing the level of clinically relevant applied musculotendinous force from 5 to 17 N during the immediate postoperative period did not accelerate the timedependent accrual of repair site strength or stiffness. Suture technique was of primary importance, however, in providing a strong and stiff repair site throughout the early healing interval. These findings suggested that there be a re-evaluation of the concept that increases in force provided by more vigorous rehabilitation techniques are beneficial to early tendon healing. Even in the context of modern eight-strand suture repair techniques, increased applied force might potentially increase the incidence of repair site dehiscence or gap formation, and is not advocated at present.
The effects of increased in vivo tendon excursion (independent of applied musculotendinous force) on digital range of motion and tendon strength after flexor digitorum profundus (FDP) tendon transection and repair were evaluated as well.63 Ninety-six FDP tendons were injured, repaired and treated by lowforce (5 N) passive mobilization rehabilitation protocols starting on the first postoperative day. The protocols held the applied force constant but varied the excursion achieved: 1.7 mm of intrasynovial excursion for the low-excursion group, and 3.5 mm for the high-excursion group. Rehabilitation for the first group (low force/low excursion) consisted of passive flexion and extension of the four digits with the wrist maintained in the flexed position; for the second group (low force/high excursion) the wrist and digits flexed and extended simultaneously. Our results indicated that the use of rehabilitation that produced increased tendon excursion within the context of low applied force did not influence range-of-motion or tensile properties. Joint rotation and tendon excursion in digits from the low-force/ low-excursion and low-force/high-excursion groups were not significantly different ( p > 0.05), with both groups not significantly different from unoperated controls. Tensile structural properties (ultimate force, rigidity, strain at 20 N, strain at failure) were not significantly affected by increased excursion ( p > 0.05). We conclude that a threshold of 1.7 mm of tendon excursion is sufficient to inhibit adhesion formation and to allow excellent recovery of functional properties following sharp transection of the canine FDP tendon. Additional excursion, at the same low force level, appeared to provide little added benefit. These results contrast those recently reported by Zhao et al.,64 who demonstrated in an in vivo canine model of partial tendon laceration and repair that, based on improvements in adhesion breaking strength and decreased overall formation of adhesions, synergistic wrist motion coupled with passive digital flexion was beneficial to tendon healing and digital motion. Although the model utilized was one of partial tendon laceration and repair wherein the force required to rupture the repair site averaged a minimum of 135 N (over seven times that force applied during clinically relevant high-force rehabilitation), the implication is that increased tendon excursion within the context of low applied force may be of benefit in the minimization of the formation of intrasynovial adhesions.
SUMMARY Based on presently available experimental and clinical data, we conclude that primary repair of a intrasynovial flexor tendon laceration65 using a modern multistrand core and epitendinous suture April–June 2005
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technique27 should be able to withstand repair site gap formation of 3 mm during the first three postoperative weeks.57 A passive motion rehabilitation protocol that strives to emphasize intrasynovial repair site excursion,63 rather than increased application of musculotendinous force62 across the repair site, should be utilized.66 We currently perform an eight-strand, locked repair using a synthetic, coated suture supplemented by an epitendinous running repair within ten to 14 days of injury. Therapy begins on postoperative day 1 with a synergistic protocol. Early motion is protected by a hinged splint, with wrist extension typically blocked at 30 degrees and MP extension typically blocked at 70 degrees. Early place and hold is also utilized. Close coordination between the therapist and surgeon helps to maximize outcome by modifying the rehabilitation protocol for the individual patient as necessary.
REFERENCES 1. Kessler I, Nissim F. Primary repair without immobilization of flexor tendon division within the digital sheath. An experimental and clinical study. Acta Orthop Scand. 1969;40:587–601. 2. Verdan C. Primary repair of flexor tendons. J Bone Joint Surg Am. 1960;42:647–57. 3. Gelberman RH, Manske PR, Akeson WH, Woo SL, Lundborg G, Amiel D. Flexor tendon repair. J Orthop Res. 1986;4:119–28. 4. Lundborg G. Experimental flexor tendon healing without adhesion formation—a new concept of tendon nutrition and intrinsic healing mechanisms. A preliminary report. Hand. 1976;8:235–8. 5. Lundborg G, Rank F. Experimental intrinsic healing of flexor tendons based upon synovial fluid nutrition. J Hand Surg [Am]. 1978;3:21–31. 6. Lundborg G, Rank F. Tendon healing: intrinsic mechanisms. In: Hunter J, Schneider L, Mackin E (eds). Tendon Surgery in the Hand. St. Louis: CV Mosby, 1987, pp 54–60. 7. Matthews P, Richards H. Factors in the adherence of flexor tendon after repair: an experimental study in the rabbit. J Bone Joint Surg Br. 1976;56:618–25. 8. Gelberman RH, Amifl D, Gonsalves M, Woo S, Akeson WH. The influence of protected passive mobilization on the healing of flexor tendons: a biochemical and microangiographic study. Hand. 1981;13:120–8. 9. Gelberman RH, Woo SL, Lothringer K, Akeson WH, Amiel D. Effects of early intermittent passive mobilization on healing canine flexor tendons. J Hand Surg [Am]. 1982;7:170–5. 10. Woo SL, Gelberman RH, Cobb NG, Amiel D, Lothringer K, Akeson WH. The importance of controlled passive mobilization on flexor tendon healing. A biomechanical study. Acta Orthop Scand. 1981;52:615–22. 11. Duran R, Houser R, Coleman C, Postlewaite D. A preliminary report in the use of controlled passive motion following flexor tendon repair in zones II and III (abstract). J Hand Surg. 1976; 1:79. 12. Duran RJ, Houser RG. Controlled passive motion following flexor tendon repair in zones 2 and 3. In: AAOS Symposium on Tendon Surgery in the Hand. St. Louis: CV Mosby, 1975, pp 105–14. 13. Lister GD, Kleinert HE, Kutz JE, Atasoy E. Primary flexor tendon repair followed by immediate controlled mobilization. J Hand Surg [Am]. 1977;2:441–51. 14. Kleinert HE, Kutz JE, Atasoy E, Stormo A. Primary repair of flexor tendons. Orthop Clin North Am. 1973;4:865–76.
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15. Strickland JW, Glogovac SV. Digital function following flexor tendon repair in Zone II: A comparison of immobilization and controlled passive motion techniques. J Hand Surg [Am]. 1980; 5:537–43. 16. Horii E, Lin GT, Cooney WP, Linscheid RL, An KN. Comparative flexor tendon excursion after passive mobilization: an in vitro study. J Hand Surg [Am]. 1992;17:559–66. 17. Hitchcock TF, Light TR, Bunch WH, et al. The effect of immediate constrained digital motion on the strength of flexor tendon repairs in chickens. J Hand Surg [Am]. 1987;12: 590–5. 18. Mason ML, Allen HS. The rate of healing of tendons: an experimental study of tensile strength. Ann Surg. 1941;113: 424–59. 19. Lindsay W, Thompson H, Walker H. Digital flexor tendons: an experimental study. Br J Plast Surg. 1960;13:1–9. 20. Ketchum LD. Primary tendon healing: a review. J Hand Surg. 1977;2:428–35. 21. Ketchum LD, Martin NL, Kappel DA. Experimental evaluation of factors affecting the strength of tendon repairs. Plast Reconstr Surg. 1977;59:708–19. 22. Seradge H. Elongation of the repair configuration following flexor tendon repair. J Hand Surg [Am]. 1983;8:182–5. 23. Potenza A. Concepts of tendon healing and repair. In: AAOS Symposium on Tendon Surgery in the Hand. St. Louis: CV Mosby, 1975, pp 18–47. 24. Potenza A. Philosophy of flexor tendon surgery. Orthop Clin North Am. 1986;17:349–52. 25. Peacock E. Fundamental aspect of wound healing relating to the restoration of gliding function after tendon repair. Surg Gynecol Obstet. 1964;119:241–50. 26. Peacock E. Biological principles in the healing of long tendons. Surg Clin North Am. 1965;45:461–76. 27. Winters SC, Gelberman RH, Woo SL-Y, Chan SS, Grewal R, Seiler JG. The effects of multiple-strand suture methods on the strength and excursion of repaired intrasynovial flexor tendon: a biomechanical study in dogs. J Hand Surg [Am]. 1998;23: 97–104. 28. Winters SC, Seiler JG III, Woo SL, Gelberman RH. Suture methods for flexor tendon repair. A biomechanical analysis during the first six weeks following repair. Ann Chir Main Memb Super. 1997;16:229–34. 29. Taras J, Skahen J, James R, Raphael J, Marzyk S, Bauerle W. The double-grasping and cross-stitch for acute flexor tendon repair: Applications with active motion. Atlas Hand Clin. 1996;1:13–28. 30. Savage R. In vitro studies of a new method of flexor tendon repair. J Hand Surg [Br]. 1985;10:135–41. 31. Lin GT, An KN, Amadio PC. Cooney WP III. Biomechanical studies of running suture for flexor tendon repair in dogs. J Hand Surg [Am]. 1988;13:553–8. 32. Wagner WF Jr, Carroll Ct, Strickland JW, Heck DA, Toombs JP. A biomechanical comparison of techniques of flexor tendon repair. J Hand Surg [Am]. 1994;19:979–83. 33. Kessler I. The ‘‘grasping’’ technique for tendon repair. Hand. 1973;5:253–5. 34. Tajima T. History, current status, and aspects of hand surgery in Japan. Clin Orthop. 1984;184:41–9. 35. Strickland JW. Flexor tendon repair. Hand Clin. 1985;1:55–68. 36. Strickland J. Flexor tendon repair: Indiana method. Indiana Hand Center Newsletter. 1993;1:1–12. 37. Strickland JW. Flexor tendon injuries: II. Operative technique. J Am Acad Orthop Surg. 1995;3:55–62. 38. McLarney E, Hoffman H, Wolfe SW. Biomechanical analysis of the cruciate four-strand flexor tendon repair. J Hand Surg [Am]. 1999;24:295–301. 39. Becker H. Primary repair of flexor tendons in the hand without immobilization: preliminary report. Hand. 1978;10:37–47. 40. Harris E, Bass B, Walker L. Tensile strength and stress-strain relationships in cadaveric human tendons [abstract]. Anat Rec. 1964;148:289. 41. Gillard GC, Reilly HC, Bell-Booth PG, Flint MH. The influence of mechanical forces on the glycosaminoglycan content of the
42.
43.
44.
45.
46.
47.
48.
49.
50.
51.
52. 53.
54.
55.
rabbit flexor digitorum profundus tendon. Connect Tissue Res. 1979;7:37–46. Mass DP, Tuel RJ, Labarbera M, Greenwald DP. Effects of constant mechanical tension on the healing of rabbit flexor tendons. Clin Orthop. 1993;296:301–6. Slack CM, Flint MH, Thompson BM. The effect of tensional load on isolated embryonic chick tendons in organ culture. Connect Tissue Res. 1984;12:229–47. Woo SL, Gomez MA, Amiel D, Ritter MA, Gelberman RH, Akeson WH. The effects of exercise on the biomechanical and biochemical properties of swine digital flexor tendons. J Biomech Eng. 1981;103:51–6. Becker H, Graham MF, Cohen IK, Diegelmann RF. Intrinsic tendon cell proliferation in tissue culture. J Hand Surg [Am]. 1981;6:616–9. Almekinders L, Banes A, Ballenger C. Effects of repetitive motion on human fibroblasts. Med Sci Sports Exer. 1993;25: 603–7. Feehan LM, Beauchene JG. Early tensile properties of healing chicken flexor tendons: early controlled passive motion versus postoperative immobilization. J Hand Surg [Am]. 1990;15:63–8. Small JO, Brennen MD, Colville J. Early active mobilisation following flexor tendon repair in zone 2. J Hand Surg [Br]. 1989;14:383–91. Schuind F, Garcia-Elias M, Cooney WP III, An KN. Flexor tendon forces: in vivo measurements. J Hand Surg [Am]. 1992; 17:291–8. Lieber RL, Amiel D, Kaufman KR, Whitney J, Gelberman RH. Relationship between joint motion and flexor tendon force in the canine forelimb. J Hand Surg [Am]. 1996;21:957–62. Lieber RL, Silva MJ, Amiel D, Gelberman RH. Wrist and digital joint motion produce unique flexor tendon force and excursion in the canine forelimb. J Biomech. 1999;32:175–81. Cannon NM, Strickland JW. Therapy following flexor tendon surgery. Hand Clin. 1985;1:147–65. Hagberg L, Selvik G. Tendon excursion and dehiscence during early controlled mobilization after flexor tendon repair in zone II: an x-ray stereophotogrammetric analysis. J Hand Surg [Am]. 1991;16:669–80. Horibe S, Woo SL, Spiegelman JJ, Marcin JP, Gelberman RH. Excursion of the flexor digitorum profundus tendon: a kinematic study of the human and canine digits. J Orthop Res. 1990; 8:167–74. May EJ, Silfverskiold KL. Rate of recovery after flexor tendon repair in zone II. A prospective longitudinal study of 145 digits. Scand J Plast Reconstr Surg Hand Surg. 1993;27:89–94.
56. Silfverskiold KL, May EJ, Tornvall AH. Gap formation during controlled motion after flexor tendon repair in zone II: a prospective clinical study. J Hand Surg [Am]. 1992;17: 539–46. 57. Gelberman RH, Boyer MI, Brodt MD, Winters SC, Silva MJ. The effect of gap formation at the repair site on the strength and excursion of intrasynovial flexor tendons. An experimental study on the early stages of tendon-healing in dogs. J Bone Joint Surg Am. 1999;81:975–82. 58. Harwood FL, Goomer RS, Gelberman RH, Silva MJ, Amiel D. Regulation of alpha(v)beta3 and alpha5beta1 integrin receptors by basic fibroblast growth factor and platelet-derived growth factor-BB in intrasynovial flexor tendon cells. Wound Repair Regen. 1999;7:381–8. 59. Harwood FL, Monosov AZ, Goomer RS, et al. Integrin expression is upregulated during early healing in a canine intrasynovial flexor tendon repair and controlled passive motion model. Connect Tissue Res. 1998;39:309–16. 60. Boyer MI, Watson JT, Lou J, Manske PR, Gelberman RH, Cai SR. Quantitative variation in vascular endothelial growth factor mRNA expression during early flexor tendon healing: an investigation in a canine model. J Orthop Res. 2001;19: 869–72. 61. Bidder M, Towler DA, Gelberman RH, Boyer MI. Expression of mRNA for vascular endothelial growth factor at the repair site of healing canine flexor tendon. J Orthop Res. 2000;18: 247–52. 62. Boyer MI, Gelberman RH, Burns ME, Dinopoulos H, Hofem R, Silva MJ. Intrasynovial flexor tendon repair. An experimental study comparing low and high levels of in vivo force during rehabilitation in canines. J Bone Joint Surg Am. 2001;83:891–9. 63. Silva MJ, Brodt MD, Boyer MI, et al. Effects of increased in vivo excursion on digital range of motion and tendon strength following flexor tendon repair. J Orthop Res. 1999;17:777–83. 64. Zhao C, Amadio PC, Momose T, Couvreur P, Zobitz ME, An KN. Effect of synergistic wrist motion on adhesion formation after repair of partial flexor digitorum profundus tendon lacerations in a canine model in vivo. J Bone Joint Surg Am. 2002;84:78–84. 65. Gelberman RH, Siegel DB, Woo SL, Amiel D, Takai S, Lee D. Healing of digital flexor tendons: importance of the interval from injury to repair. A biomechanical, biochemical, and morphological study in dogs. J Bone Joint Surg Am. 1991;73: 66–75. 66. Silva MJ, Boyer MI, Gelberman RH. Recent progress in flexor tendon healing. J Orthop Sci. 2002;7:508–14.
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