Abstract

Introduction

Despite advances in knowledge and refinements of technique, the management of flexor tendon injuries within the digital sheath continues to present a formidable challenge. This in turn has led to a massive expansion in search of modified surgical therapies and various adjuvant therapies, which could prevent adhesion formation without compromising digital function.

Sources of data

A search of PubMed, Medline, CINAHL and Embase databases was performed using the keywords ‘tendon adhesion prevention’, ‘tendon healing’, ‘adhesion prevention in tendons’ and ‘adjuvants for adhesion prevention’. Studies detailing the use of surgical, pharmacological and non-pharmacological agents for adhesion prevention in digital flexor tendons were identified, and their bibliographies were thoroughly reviewed to identify further related articles. This search identified 41 studies, which investigated the use of various pharmacological agents in adhesion prevention in digital tendons.

Areas of agreement

There is a need to develop and utilize an optimal method for the prevention of adhesions in the flexor tendons of the hand, due to post-surgical complications.

Areas of controversy

Even though there have been significant advances in the prevention of adhesions in flexor tendons, it remains to be proved which, if any, of the current methods are the most beneficial.

Growing points

The only thing that appears clinically justified in adhesion prevention is the need for early post-operative mobilization of digits after tendon injury or repair but the best method of mobilization remains controversial.

Areas timely for developing research

Suggested changes in surgical techniques and various proposed pharmacological and non-pharmacological modalities need to withstand the test of adequately powered human trials, before their justification for potential benefit in clinical practice is accepted.

Introduction

Peritendinous adhesions after repair of an injury to the digital flexor tendons are a major problem in hand surgery. The adhesions are part of the healing process and almost inevitably produce functional disability following the biological response of the tendon to injury.1 To achieve better gliding function of the digital tendons by reducing peritendinous adhesions without adversely affecting the healing process, several options, including physical, surgical and pharmacological, have been explored. This has led to the introduction of several new surgical techniques and various pharmacological and non-pharmacological modalities. However, the scientific evidence behind these methods should be thoroughly scrutinized before they are widely incorporated into routine clinical practice. This article reviews these options, and evaluates the scientific evidence behind them.

Methods

A search of PubMed, Medline, CINAHL and Embase databases was performed using the keywords ‘tendon adhesion prevention’, ‘tendon healing’, ‘adhesion prevention in tendons’ and ‘adjuvants for adhesion prevention’. Studies detailing the use of surgical, pharmacological and non-pharmacological agents for adhesion prevention in digital flexor tendons were identified, and their bibliographies were thoroughly reviewed to identify further related articles. This search identified 41 studies (demonstrated in Fig. 1), which investigated the use of various pharmacological agents in adhesion prevention in digital tendons.

Fig. 1

Flow diagram of literature search strategy.

Fig. 1

Flow diagram of literature search strategy.

Exclusion criteria

We excluded studies in language other than English, studies not dealing with digital tendons, studies not reporting on adhesion prevention along with case reports and letters to editor.

Tendon healing and adhesion formation

Collagen constitutes the main part of the tendon, with water, proteoglycans and cells forming the matrix. There is a change in the composition of proteoglycan produced by cells in the pressure-bearing areas compared with tendon-transmitting areas. Chondroitin sulphate is predominant in the pressure contact areas, whereas dermatan sulphate is dominant in the tension-transmitting segments, i.e. the areas of the tendon being stretched and becoming taut. It therefore seems likely that the differences in the type and proportion of proteoglycans in the tension and pressure-bearing segments of the tendon are related to the functional needs of the tissue, and thus may influence the formation of adhesions following tendon injury and repair.2

Intrinsic and extrinsic healing

Tendon healing proceeds by a combination of intrinsic and extrinsic processes that occur simultaneously. Intrinsic healing occurs within the tendon as a result of the activity of tenocytes and appropriate nutrition to them. Extrinsic healing occurs through the chemotaxis of the specialized fibroblasts into the defect from the ends of the tendon sheath.3,4 Synovial fluid diffusion also contributes to intrinsic healing by providing an additional nutritional source.4–10

Risk factors for adhesion formation

Matthews et al.3 noted that the tendon injury itself was not the sole stimulus for the development of adhesions. When flexor tendons were severed, the ends retracted and became rounded, lying freely within the sheath with no adhesions. Similarly, immobilization itself did not lead to an adhesive response from the digital sheath. However, excision of the synovial sheath followed by immobilization most frequently resulted in adhesive response. Also, greater degrees of trauma to the synovial sheath and gaps of 3 mm or more have been related to increased adhesion formation.3,11

The degree and extent of tendon adhesions

Siegler et al.12 classified the degree and extent of adhesions into four grades: Grade 0, complete absence of adhesions; Grade I, thin avascular, filmy and easily separable; Grade II, thick, avascular and limited to the site of anastomosis; Grade III, thick, vascular and extensive. This classification has been used for evaluation of severity of adhesion formation in various human and animal models.

Available options

With increasing information available concerning the nature of the scar tissue responsible for the peritendinous adhesions, along with changes in surgical and post-operative rehabilitation techniques, several modalities, such as modulation of inflammatory response and growth factors that promote scarring by various pharmacological agents, introduction of mechanical barriers between the tendons and the proliferating tissue, use of ultrasound and electromagnetic therapy and, recently, gene therapy, are being explored.

Modifications in surgical technique

Enhanced appreciation of tendon structure, nutrition and biomechanical properties and investigation of factors involved in tendon healing and adhesion formation have resulted in various modifications of surgical technique in handling tendon injuries.

Multistrand repair

The initial strength of tendon repair is roughly proportional to the number of suture strands that cross the repair site. The most commonly used technique involves a two-strand repair.13 Increasingly, four-, six- and even eight-strand repairs are now used,13 allowing more aggressive early rehabilitation without a greater rupture rate. Generally, the greater the number of suture strands that cross the repair site, the more technically demanding the technique, the greater the amount of surgical handling of the tendon and the greater the amount of suture material on the outside of the tendon.14,15

There is a limited information about the effect of increasing strand numbers on the healing or adhesion response in a repair. High friction suture techniques may cause more adhesion formation than the lower friction suture techniques following passive post-operative therapy.16 Strick et al.,17 however, did not find a difference. Most studies (Table 1) on gliding resistance after various suturing techniques are in vitro or animal studies. We were not able to identify any human trials.16–20

Table 1

Surgical options.

Reference Year Subjects Study design Results 
Multistrand repair 
Zhao116 2001 Canine model Sixty FDP tendons repaired with either a modified Kessler or Becker suture technique and supplemented with a simple running suture High friction suture techniques may cause more adhesion formation than the lower friction suture techniques under passive post-operative therapy 
Dinopoulos117 2000 Canine model Twenty-two flexor tendons were repaired using the 4- and an 8-strand suture technique, and tested to failure after 10 days of in vivo healing 8-strand repair is significantly more resistant to initial gapping during ex vivo tensile testing than the 4-strand repair 
Gill19 1999 Fresh-frozen human hands Forty flexor tendons were harvested from fresh-frozen human hands and divided into 4 groups of 10 tendons each. Each group of tendons was repaired with a specific technique: group 1, the modified Kirchmayr (modified Kessler) technique; group 2, the single-loop 2-strand technique described by Tsuge; group 3, Tsai's double-loop 4-strand modification of Tsuge's technique; and group 4, Tsai's double-loop 6-strand modification of Tsuge's technique The 6-strand double-loop suture technique improves the repair's strength and its resistance to gapping without increasing tendon handling or bulk 
Thurman20 1998 Cadaver models The 2- and 4-strand core sutures were placed using a suture interlock technique with radial and ulnar grasping purchase of the tendon on each side of the transverse part of the repair The tensile strength of the 6-strand repair (mean, 78.7 N) was significantly greater than either the 4-strand (means, 43.0 N) or 2-strand (mean, 33.9 N) repair 
Strick17 2004 Chicken model The FDP tendon of the right middle toe of 80 broiler chickens was cut and then repaired with either a single (2-strand) or double (4-strand) modified Kessler core suture, followed by a running epitendinous suture Adhesion formation and gliding resistance of tendons after 2- or 4-strand modified Kessler core suture were not significantly different 
Tendon sheath: to repair or not to repair? 
Peterson32 1986 Chicken model Tendon gliding of flexor sheath excision versus incision/closure following primary flexor tendon repair was examined biomechanically and histologically in 41 chickens There was no significant difference in either the tendon excursion required to fully flex the digit or in the work of flexion between the sheath excised and sheath closed groups 
Strauch31 1985 Chicken model Sheath closure after tendon grafting was accomplished by trapdoor of the original sheath, vein patch and vein conduit Significantly greater functional return when the sheath was restored either with trap-door closure, vein conduit or vein patch compared with simple excision of the sheath 
Saldana33 1987 Patients with lacerations of both flexor tendons A modified Kessler suture was used to repair the profundus tendon. The tendon of superficialis tendon was repaired with a horizontal mattress suture. In 48 fingers, the flexor tendon sheath was left open and it was closed in the second group of 42 fingers There was no statistical difference between the results of open sheath versus closed sheath in these two groups of patients 
Gelberman34 1990 Canine model Flexor sheath repair, sheath excision and autogenous sheath grafting were compared for biomechanical characteristics, and biochemical and ultrastructural alterations at the repair site at intervals over a 12-week period Reconstruction of the tendon sheath, either by suture or autogenous graft, did not improve significantly the biomechanical, biochemical or morphologic characteristics of repaired tendons treated with early motion rehabilitation 
Peterson35 1990 Chicken model Three methods of sheath closure. I. Primary sheath repair; II. a fascia patch; III. a synthetic polytetrafluoroethylene surgical membrane patch, were compared with controls in which the flexor sheath was excised At 3 and 6 weeks there was no significant difference in the work of flexion between either the sheath repair or fascia patch digits, and the sheath excised controls. In contrast, at 12 weeks all three methods of sheath reconstruction had similar tendon gliding biomechanics, and all were significantly better than the controls 
Tang36 1994 Leghorn chickens In the left foot, the tendon sheath was closed after tendon suture. In the right foot, the sheath was excised over the tendon suture The sutured sheath disappeared after suturing and was associated with poor tendon healing. Sheath closure did not improve flexor tendon function in a delayed primary repair 
Post-operative mobilization 
Adolfsson39 1996 Humans Injured tendons were repaired within 24 h, and all patients were subjected to mobilization during the first 6 weeks using a passive flexion-active extension regime. After 6 weeks the patients were randomized into two groups; in group A full activity was allowed after 8 weeks while in group B unrestricted use of the injured hand was not allowed until 10 weeks after the tendon repair No significant differences were observed between the groups regarding functional results, rupture rates, grip strength or subjective assessment, but absence from work was reduced by 2.1 weeks with the shorter mobilization programme 
Gelberman40 1991 Humans Fifty-one patients were randomly allocated to two controlled passive motion protocols. Group 1 patients received greater intervals of passive-motion rehabilitation using a continuous passive-motion device. Group 2 patients were treated with a traditional early passive-motion protocol for tendon rehabilitation Duration of the daily controlled motion interval is a significant variable insofar as post-repair flexor tendon function is concerned 
    Using Strickland and Glogovac's formula, the mean active motion for digits in Group 1 was 138 degrees ± 6 degrees. Mean motion for tendons in Group 2 was 119 degrees ± 8 degrees. The difference between Groups 1 and 2 was statistically significant. The effect of the number of tendons injured per digit within each group was not significant 
Percival41 1989 Humans Fifty-one patients with isolated flexor pollicis longus tendon repairs were divided into two groups. I. was kept immobile; II. Underwent controlled dynamic mobilisation The results of mobilisation were significantly better, with 62% achieving good or excellent results compared to 33% treated by fixed splintage 
Pulley incision and pulley plasty 
Tang45 2007 Leghorn chickens 52 leghorn chickens were divided into four experimental groups and one control group. An in vitro study was conducted to investigate the biomechanical effects of pulley incision, Kapandji pulley plasty, excision of one slip of the FDS or closure of the incised pulley on function of the profundus tendons Eight weeks after surgery, incision of the pulley improved excursion of the digitorum profundus tendon and decreased the work of digital flexion over pulley closure. Kapandji pulley plasty did not increase tendon excursion and decrease the work compared with a simpler pulley incision. Adhesions were more severe with pulley plasty closure than with pulley incision. Kapandji pulley plasty did not improve outcomes over simple pulley incision 
Simultaneous repair 
Tang46 1994 Humans A study was carried out in 33 patients (37 fingers) with lacerations of both FDS and FDP tendons in the area covered by the A2 pulley. Both lacerated tendons were repaired in 19 fingers, and repair of only FDP with regional excision of FDS was performed in 18 fingers Follow-up of at an average of 12 months showed no significant difference in the end results. The fingers with suture of both tendons showed a higher rate of re-operation due to adhesions or rupture of repair. This study suggests that it is better to repair only FDP with regional excision of FDS when both tendons are injured in zone 2C 
Reference Year Subjects Study design Results 
Multistrand repair 
Zhao116 2001 Canine model Sixty FDP tendons repaired with either a modified Kessler or Becker suture technique and supplemented with a simple running suture High friction suture techniques may cause more adhesion formation than the lower friction suture techniques under passive post-operative therapy 
Dinopoulos117 2000 Canine model Twenty-two flexor tendons were repaired using the 4- and an 8-strand suture technique, and tested to failure after 10 days of in vivo healing 8-strand repair is significantly more resistant to initial gapping during ex vivo tensile testing than the 4-strand repair 
Gill19 1999 Fresh-frozen human hands Forty flexor tendons were harvested from fresh-frozen human hands and divided into 4 groups of 10 tendons each. Each group of tendons was repaired with a specific technique: group 1, the modified Kirchmayr (modified Kessler) technique; group 2, the single-loop 2-strand technique described by Tsuge; group 3, Tsai's double-loop 4-strand modification of Tsuge's technique; and group 4, Tsai's double-loop 6-strand modification of Tsuge's technique The 6-strand double-loop suture technique improves the repair's strength and its resistance to gapping without increasing tendon handling or bulk 
Thurman20 1998 Cadaver models The 2- and 4-strand core sutures were placed using a suture interlock technique with radial and ulnar grasping purchase of the tendon on each side of the transverse part of the repair The tensile strength of the 6-strand repair (mean, 78.7 N) was significantly greater than either the 4-strand (means, 43.0 N) or 2-strand (mean, 33.9 N) repair 
Strick17 2004 Chicken model The FDP tendon of the right middle toe of 80 broiler chickens was cut and then repaired with either a single (2-strand) or double (4-strand) modified Kessler core suture, followed by a running epitendinous suture Adhesion formation and gliding resistance of tendons after 2- or 4-strand modified Kessler core suture were not significantly different 
Tendon sheath: to repair or not to repair? 
Peterson32 1986 Chicken model Tendon gliding of flexor sheath excision versus incision/closure following primary flexor tendon repair was examined biomechanically and histologically in 41 chickens There was no significant difference in either the tendon excursion required to fully flex the digit or in the work of flexion between the sheath excised and sheath closed groups 
Strauch31 1985 Chicken model Sheath closure after tendon grafting was accomplished by trapdoor of the original sheath, vein patch and vein conduit Significantly greater functional return when the sheath was restored either with trap-door closure, vein conduit or vein patch compared with simple excision of the sheath 
Saldana33 1987 Patients with lacerations of both flexor tendons A modified Kessler suture was used to repair the profundus tendon. The tendon of superficialis tendon was repaired with a horizontal mattress suture. In 48 fingers, the flexor tendon sheath was left open and it was closed in the second group of 42 fingers There was no statistical difference between the results of open sheath versus closed sheath in these two groups of patients 
Gelberman34 1990 Canine model Flexor sheath repair, sheath excision and autogenous sheath grafting were compared for biomechanical characteristics, and biochemical and ultrastructural alterations at the repair site at intervals over a 12-week period Reconstruction of the tendon sheath, either by suture or autogenous graft, did not improve significantly the biomechanical, biochemical or morphologic characteristics of repaired tendons treated with early motion rehabilitation 
Peterson35 1990 Chicken model Three methods of sheath closure. I. Primary sheath repair; II. a fascia patch; III. a synthetic polytetrafluoroethylene surgical membrane patch, were compared with controls in which the flexor sheath was excised At 3 and 6 weeks there was no significant difference in the work of flexion between either the sheath repair or fascia patch digits, and the sheath excised controls. In contrast, at 12 weeks all three methods of sheath reconstruction had similar tendon gliding biomechanics, and all were significantly better than the controls 
Tang36 1994 Leghorn chickens In the left foot, the tendon sheath was closed after tendon suture. In the right foot, the sheath was excised over the tendon suture The sutured sheath disappeared after suturing and was associated with poor tendon healing. Sheath closure did not improve flexor tendon function in a delayed primary repair 
Post-operative mobilization 
Adolfsson39 1996 Humans Injured tendons were repaired within 24 h, and all patients were subjected to mobilization during the first 6 weeks using a passive flexion-active extension regime. After 6 weeks the patients were randomized into two groups; in group A full activity was allowed after 8 weeks while in group B unrestricted use of the injured hand was not allowed until 10 weeks after the tendon repair No significant differences were observed between the groups regarding functional results, rupture rates, grip strength or subjective assessment, but absence from work was reduced by 2.1 weeks with the shorter mobilization programme 
Gelberman40 1991 Humans Fifty-one patients were randomly allocated to two controlled passive motion protocols. Group 1 patients received greater intervals of passive-motion rehabilitation using a continuous passive-motion device. Group 2 patients were treated with a traditional early passive-motion protocol for tendon rehabilitation Duration of the daily controlled motion interval is a significant variable insofar as post-repair flexor tendon function is concerned 
    Using Strickland and Glogovac's formula, the mean active motion for digits in Group 1 was 138 degrees ± 6 degrees. Mean motion for tendons in Group 2 was 119 degrees ± 8 degrees. The difference between Groups 1 and 2 was statistically significant. The effect of the number of tendons injured per digit within each group was not significant 
Percival41 1989 Humans Fifty-one patients with isolated flexor pollicis longus tendon repairs were divided into two groups. I. was kept immobile; II. Underwent controlled dynamic mobilisation The results of mobilisation were significantly better, with 62% achieving good or excellent results compared to 33% treated by fixed splintage 
Pulley incision and pulley plasty 
Tang45 2007 Leghorn chickens 52 leghorn chickens were divided into four experimental groups and one control group. An in vitro study was conducted to investigate the biomechanical effects of pulley incision, Kapandji pulley plasty, excision of one slip of the FDS or closure of the incised pulley on function of the profundus tendons Eight weeks after surgery, incision of the pulley improved excursion of the digitorum profundus tendon and decreased the work of digital flexion over pulley closure. Kapandji pulley plasty did not increase tendon excursion and decrease the work compared with a simpler pulley incision. Adhesions were more severe with pulley plasty closure than with pulley incision. Kapandji pulley plasty did not improve outcomes over simple pulley incision 
Simultaneous repair 
Tang46 1994 Humans A study was carried out in 33 patients (37 fingers) with lacerations of both FDS and FDP tendons in the area covered by the A2 pulley. Both lacerated tendons were repaired in 19 fingers, and repair of only FDP with regional excision of FDS was performed in 18 fingers Follow-up of at an average of 12 months showed no significant difference in the end results. The fingers with suture of both tendons showed a higher rate of re-operation due to adhesions or rupture of repair. This study suggests that it is better to repair only FDP with regional excision of FDS when both tendons are injured in zone 2C 

Tendon sheath: to repair or not to repair?

Sheath closure following flexor tendon repair is frequently attempted.21 This practice is largely based on the concepts that flexor tendons within the region of synovial sheaths are mainly nourished through synovial diffusion,22 and that lacerated tendons can heal sufficiently through their intrinsic cellular activities without the necessity of adhesion formation.23 Restoration of sheath integrity is believed to preserve nutrition of the tendons, provide them with a smooth gliding surface for tendons, and decrease peritendinous adhesions.21–30

There are conflicting views on the advantages of sheath closure (Table 1). Restoration of sheath integrity in flexor tendons reduces adhesion formation.31 However, sheath closure has not proved consistently effective in improving tendon gliding function.32–35 For example, the sutured sheath may disappear after suturing, and is associated with poor tendon healing.36 In a human trial,32 no statistical difference between the results of leaving the sheath open versus closing it in two groups of patients was noticed.

Post-operative mobilization

Post-operative mobilization decreases adhesion formation and improves function after flexor tendon repair.37,38 There are now several post-operative mobilization regimes like shortened passive flexion/active extension versus normal passive flexion/active extension;39 continuous passive motion versus controlled intermittent passive motion;40 dynamic splintage versus static splintage;41 active flexion versus rubber band traction;42 controlled passive flexion with active extension (modified Kleinert) versus controlled passive mobilization (modified Duran);43 grasping suture and early controlled active mobilization versus modified Kessler technique with early controlled passive mobilization44 to improve gliding function of tendons (Table 1).

There is, however, insufficient evidence from randomized, controlled trials to define the best mobilization strategy.

Pulley incision and pulley plasty

Outcomes of flexor tendon repairs in the area covered by major pulleys are often unpredictable. Tang et al.45 showed that incision of the pulley-improved excursion of the flexor digitorum profundus (FDP) tendon and decreased the work of digital flexion over pulley closure. Kapandji pulley plasty did not increase tendon excursion and decrease the work compared with a simpler pulley incision. Adhesions were more severe with pulley plasty or closure than with pulley incision (Table 1).

Simultaneous repair

Tang46 studied 33 patients (37 fingers) with lacerations of both flexor digitorum superficialis (FDS) and FDP tendons in the area covered by the A2 pulley. Both lacerated tendons were repaired in 19 fingers, and repair of only FDP with regional excision of FDS was performed in 18 fingers. Follow-up of average 12 months revealed that there was no significant difference in the end results. The study suggests that it is better to repair only FDP with regional excision of FDS when both tendons are injured in zone 2C (Table 1).

Pharmacological adjuvants

Several pharmacological adjuvants have evolved in the search to find the answer to rapid recovery and function in hand tendons after injury or surgery. These adjuvants fall into two main categories, namely drugs and barriers.

Drugs

Non-steroidal anti-inflammatory medications

Mechanism of action and role in adhesion prevention

Non-steroidal anti-inflammatory drugs (NSAIDS) competitively inhibit cyclo-oxygenase, an enzyme essential for the metabolism of arachidonic acid (AA) to prostaglandins. The end products and intermediate metabolites of AA metabolism are involved in the inflammatory process, ultimately leading to adhesion formation.47

The net effect of treatment with NSAIDS is to decrease the metabolites and by-products of AA metabolism and, consequently, their effects on the local tissues. By reducing these pro-inflammatory agents, endogenous local damage may be decreased after trauma. The consequence could be a decrease in peritendinous fibroplasias.47

Supporting evidence

Several studies have shown that NSAIDS appears to inhibit the formation of significant post-operative adhesion in a dose-dependent fashion when compared with control subjects (Table 2).47,48 Also, ibuprofen treatment did not appear to inhibit normal wound healing, nor did it cause abnormal bleeding or oozing at the operative site.48

Table 2

Pharmacological modalities and other therapeutic options.

Reference Year Subjects Study design Results 
Drugs 
 Mode of HA use 
 Tanaka103 2007 Canine model Surface treatment of tendons with carbodiimide-derivatized HA (cd-HA) The adhesion score of cd-HA gelatin-treated tendons was significantly less than that in the saline-treated tendons at all times. However, there was no significant difference in strength at the distal tendon-bone interface, cellularity or tendon graft stiffness when comparing saline-treated and cd-HA treated tendon grafts in vivo 
 Zhao104 2006 Canine model Surface treatment of flexor tendon autografts with cd-HA Treating the surface of an extra synovial tendon autograft with a cd-HA-gelatin polymer decreases digital work of flexion and tendon gliding resistance in flexor tendon graft model in vivo 
 Akasaka105 2005 Canine model HA injected around the tendon HA diminishes the excursion resistance after flexor tendon repair 
 Hagberg51 1992 Humans HA injected around the tendon Sodium hyaluronate had no statistically significant effect as evaluated by total active motion 
 Mode of Ibuprofen use 
 Kulick47 1984 Cynomolgus monkeys Group I. Peritendinous injections of 0.1 ml of ibuprofen every 12 h for 10 days to the 8 FDP tendons In weeks 1–3, fewer inflammatory and reactive cells were observed in the ibuprofen-treated digits compared with control and standard digits 
   Group II. Oral ibuprofen, 75 mg/kg, every 12 h for 10 days and peritendinous injections of 0.1 ml of ibuprofen every 12 h for 10 days to the 8 FDP tendons  
    The animal treated with supplemental oral ibuprofen showed a major reduction in peak force in the digits affected as compared to systemic medication alone 
 Kulick106 1986 Cynomolgus monkeys Orally dosing of one of the four following doses: 25, 35, 45 and 75 mg/kg/day of ibuprofen Treatment with oral ibuprofen significantly reduced the force required for tendon gliding following flexor tendon injury in zone II 
 Szabo107 1990 New Zealand white rabbits Indomethacin solution (1 mg/kg/day) injected subcutaneously 2 h before operation and daily for 4 weeks The animals treated with indomethacin had a greater tendon excursion and angular rotation of the joint than the control animals, implying suppression of adhesions 
 Mode of 5-FU use 
 Moran108 2000 Leghorn chickens 5-FU solution applied topically Histologic sections as graded by a blinded pathologist revealed decreased adhesion formation in all the 5-FU-treated animals 
    Overall, a single intra-operative application of 5-FU at concentrations of 25 mg/mL appears to be an effective mechanism for reducing post-operative flexor tendon adhesions 
 Akali53 1999 Rabbits 5-FU solution (50 mg/ml)-soaked sponge pledgets There was a significant reduction in synovial sheath thickening, cell counts and proportional length of adhesions in the treated tendons 
 Mode of HAF use 
 Ozgenel58 2001 New Zealand adult rabbits Topical application Application of HAF immediately after tenorrhaphy was effective in preventing peritendinous adhesion formation without impairment of tendon healing 
 Other pharmacological agent used 
 Chang59 2000 New Zealand white rabbits Neutralizing antibody to TGF-β1 Intra-operative biochemical modulation of TGF-beta1 levels limits flexor tendon adhesion formation. Infiltration of neutralizing antibody to TGF-beta1 improves flexor tendon excursion 
 Namba63 2007 Japanese white rabbit Surface coating of injured flexor digitorum communis tendon with alginate When compared with the control group, the alginate-treated group demonstrated significantly greater toe flexion, with less scar tissue formation at the repair site. Histologically, complete tendon healing with longitudinal remodelling of collagen fibres was observed in the alginate-treated group, while a random pattern of fibres was observed in the control group 
 McCombe64 2006 Rat In-continuity crush injury model in the rat hind foot flexor tendon to provoke adhesion formation. Animals in the treatment groups received collagen prolyl 4 hydroxylase inhibitor orally for 1, 2 or 6 weeks The cutaneous wound healing rate was similar in all animals, but dermal collagen synthesis was reduced in the treated animals 
 Jones65 2002 Rabbits Surface coating of deep flexor tendons with human-derived fibrin sealant Highly significant difference in reduction of adhesions in the treated group 
 Nyska66 1996 Chickens Surface coating of deep flexor tendons with Halofuginone Almost complete absence of fibrous peritendinous adhesions in the histologic sections of the Halofuginone treated tendons. 
    Halofuginone had no effect on the cellularity of the healing tissue 
 Speer67 1985 Lindsay chicken Topically applied beta-aminopropionitrile base Topical beta-aminopropionitrile was effective in the control of peritendinous adhesions, and achieves sufficient depth of penetration topically to affect the peritendinous location. No adverse effects of the topically applied agent were demonstrated 
 Porat69 1980 Chickens Surface coating of long flexor tendons with an aqueous solution of enriched native collagen (ECS) The exogenous collagen present at the site of injury binds the collagenase inhibitor released by tendon cells, thus providing enough active collagenase to control the formation of fibrous adhesions 
Pharmacological modalities: barriers 
Hanff73 1998 Rabbits Application of poly tetra fluoro-ethylene (e-PTFE) sheath after tendon repair in zone II The e-PTFE group showed significantly lower maximum tensile load to flex the distal interphalangeal joint 50° during the first 6 weeks after surgery, indicating less formation of restrictive adhesions compared with the control group. Tensile strength of tendon repair was similar in e-PTFE and control groups 
Peterson35 1990 Chickens Application of sheath to traumatized flexor tendons The synthetic patch (e-PTFE) was not associated with a significant inflammatory reaction at 3 weeks time period as compared to direct sheath repair or fascia patch grafted digits, and was clearly separated from the tendon 
Siddiqi74 1991 Chickens Application of hydroxyapatite (Hap) sheath to excised flexor sheath The mobility of the tendons was better in the HAp group. HAp sheath was not firmly adherent to either the granulation tissue or the surface of the tendon. Histology at 3 and 6 weeks in HAp groups revealed epitenon-like structure on the tendon surface including the tenorrhaphy, site and a wide space around the tendon after the HAp sheath was removed 
Siddiqi75 1995 Chickens Application of hydroxyapatite (Hap) and alumina sheath to injured profundus tendons in zone II Decreased severity of post-operative adhesions in the HAp as well as in the alumina groups in comparison with the sheath repair and controls 
Isik109 1999 Leghorn chickens Application of HA sheath to repaired flexor profundus tendons at zone II in the second, third and fourth toes There were few adhesions in the HA treated group microscopically at the third month as compared to control group 
Karakurum110 2003 Chickens Seprafilm (a combination of carboxymethylcellulose membrane and hyaluronate) Seprafilm was effective in preventing adhesions after tenolysis compared to control group 
Kobayashi76 2001 Domestic fowl Application of PVA-H sheath to injured deep flexor tendon of the third toe Injured tendons shielded with PVA-H healed within about 3 weeks without adhesion to the surrounding tissues. Neither breakage of the PVA-H shield itself nor infection or degeneration in the surrounding tissue was observed 
Sungur111 2006 Chickens Application of bovine pericardia to injured flexor tendons in chicken toe Significantly less adhesion formation in the bovine pericardia treated group 
Ultrasound 
Maiti77 2006 Adult goats pulsed ultrasound therapy was started 3 days after repair of tendinous injury at an intensity of 1 W/cm(2) for 10 min daily for 10 consecutive days Air tenograms and ultrasonography examinations showed that there was a marked regression of peritendinous adhesion between the tendon and skin on day 30 post-tendon injury repaired. The tendon at the repair site attained near normal thickness and density 
    Adhesions were present in the repair site of superficial digital flexor tendon in all animals of the control group 
    Histopathologically, the granulation tissue was comparatively better organized at the healing site in the ultrasound-treated animals 
Turner78 1989 Cockerel Application of ultrasound The application of ultrasound to sutured cockerel tendons produced no change in the mechanical strength of the tendon at 6 weeks, or its propensity to form adhesions, relative to untreated control sutured tendons 
Reference Year Subjects Study design Results 
Drugs 
 Mode of HA use 
 Tanaka103 2007 Canine model Surface treatment of tendons with carbodiimide-derivatized HA (cd-HA) The adhesion score of cd-HA gelatin-treated tendons was significantly less than that in the saline-treated tendons at all times. However, there was no significant difference in strength at the distal tendon-bone interface, cellularity or tendon graft stiffness when comparing saline-treated and cd-HA treated tendon grafts in vivo 
 Zhao104 2006 Canine model Surface treatment of flexor tendon autografts with cd-HA Treating the surface of an extra synovial tendon autograft with a cd-HA-gelatin polymer decreases digital work of flexion and tendon gliding resistance in flexor tendon graft model in vivo 
 Akasaka105 2005 Canine model HA injected around the tendon HA diminishes the excursion resistance after flexor tendon repair 
 Hagberg51 1992 Humans HA injected around the tendon Sodium hyaluronate had no statistically significant effect as evaluated by total active motion 
 Mode of Ibuprofen use 
 Kulick47 1984 Cynomolgus monkeys Group I. Peritendinous injections of 0.1 ml of ibuprofen every 12 h for 10 days to the 8 FDP tendons In weeks 1–3, fewer inflammatory and reactive cells were observed in the ibuprofen-treated digits compared with control and standard digits 
   Group II. Oral ibuprofen, 75 mg/kg, every 12 h for 10 days and peritendinous injections of 0.1 ml of ibuprofen every 12 h for 10 days to the 8 FDP tendons  
    The animal treated with supplemental oral ibuprofen showed a major reduction in peak force in the digits affected as compared to systemic medication alone 
 Kulick106 1986 Cynomolgus monkeys Orally dosing of one of the four following doses: 25, 35, 45 and 75 mg/kg/day of ibuprofen Treatment with oral ibuprofen significantly reduced the force required for tendon gliding following flexor tendon injury in zone II 
 Szabo107 1990 New Zealand white rabbits Indomethacin solution (1 mg/kg/day) injected subcutaneously 2 h before operation and daily for 4 weeks The animals treated with indomethacin had a greater tendon excursion and angular rotation of the joint than the control animals, implying suppression of adhesions 
 Mode of 5-FU use 
 Moran108 2000 Leghorn chickens 5-FU solution applied topically Histologic sections as graded by a blinded pathologist revealed decreased adhesion formation in all the 5-FU-treated animals 
    Overall, a single intra-operative application of 5-FU at concentrations of 25 mg/mL appears to be an effective mechanism for reducing post-operative flexor tendon adhesions 
 Akali53 1999 Rabbits 5-FU solution (50 mg/ml)-soaked sponge pledgets There was a significant reduction in synovial sheath thickening, cell counts and proportional length of adhesions in the treated tendons 
 Mode of HAF use 
 Ozgenel58 2001 New Zealand adult rabbits Topical application Application of HAF immediately after tenorrhaphy was effective in preventing peritendinous adhesion formation without impairment of tendon healing 
 Other pharmacological agent used 
 Chang59 2000 New Zealand white rabbits Neutralizing antibody to TGF-β1 Intra-operative biochemical modulation of TGF-beta1 levels limits flexor tendon adhesion formation. Infiltration of neutralizing antibody to TGF-beta1 improves flexor tendon excursion 
 Namba63 2007 Japanese white rabbit Surface coating of injured flexor digitorum communis tendon with alginate When compared with the control group, the alginate-treated group demonstrated significantly greater toe flexion, with less scar tissue formation at the repair site. Histologically, complete tendon healing with longitudinal remodelling of collagen fibres was observed in the alginate-treated group, while a random pattern of fibres was observed in the control group 
 McCombe64 2006 Rat In-continuity crush injury model in the rat hind foot flexor tendon to provoke adhesion formation. Animals in the treatment groups received collagen prolyl 4 hydroxylase inhibitor orally for 1, 2 or 6 weeks The cutaneous wound healing rate was similar in all animals, but dermal collagen synthesis was reduced in the treated animals 
 Jones65 2002 Rabbits Surface coating of deep flexor tendons with human-derived fibrin sealant Highly significant difference in reduction of adhesions in the treated group 
 Nyska66 1996 Chickens Surface coating of deep flexor tendons with Halofuginone Almost complete absence of fibrous peritendinous adhesions in the histologic sections of the Halofuginone treated tendons. 
    Halofuginone had no effect on the cellularity of the healing tissue 
 Speer67 1985 Lindsay chicken Topically applied beta-aminopropionitrile base Topical beta-aminopropionitrile was effective in the control of peritendinous adhesions, and achieves sufficient depth of penetration topically to affect the peritendinous location. No adverse effects of the topically applied agent were demonstrated 
 Porat69 1980 Chickens Surface coating of long flexor tendons with an aqueous solution of enriched native collagen (ECS) The exogenous collagen present at the site of injury binds the collagenase inhibitor released by tendon cells, thus providing enough active collagenase to control the formation of fibrous adhesions 
Pharmacological modalities: barriers 
Hanff73 1998 Rabbits Application of poly tetra fluoro-ethylene (e-PTFE) sheath after tendon repair in zone II The e-PTFE group showed significantly lower maximum tensile load to flex the distal interphalangeal joint 50° during the first 6 weeks after surgery, indicating less formation of restrictive adhesions compared with the control group. Tensile strength of tendon repair was similar in e-PTFE and control groups 
Peterson35 1990 Chickens Application of sheath to traumatized flexor tendons The synthetic patch (e-PTFE) was not associated with a significant inflammatory reaction at 3 weeks time period as compared to direct sheath repair or fascia patch grafted digits, and was clearly separated from the tendon 
Siddiqi74 1991 Chickens Application of hydroxyapatite (Hap) sheath to excised flexor sheath The mobility of the tendons was better in the HAp group. HAp sheath was not firmly adherent to either the granulation tissue or the surface of the tendon. Histology at 3 and 6 weeks in HAp groups revealed epitenon-like structure on the tendon surface including the tenorrhaphy, site and a wide space around the tendon after the HAp sheath was removed 
Siddiqi75 1995 Chickens Application of hydroxyapatite (Hap) and alumina sheath to injured profundus tendons in zone II Decreased severity of post-operative adhesions in the HAp as well as in the alumina groups in comparison with the sheath repair and controls 
Isik109 1999 Leghorn chickens Application of HA sheath to repaired flexor profundus tendons at zone II in the second, third and fourth toes There were few adhesions in the HA treated group microscopically at the third month as compared to control group 
Karakurum110 2003 Chickens Seprafilm (a combination of carboxymethylcellulose membrane and hyaluronate) Seprafilm was effective in preventing adhesions after tenolysis compared to control group 
Kobayashi76 2001 Domestic fowl Application of PVA-H sheath to injured deep flexor tendon of the third toe Injured tendons shielded with PVA-H healed within about 3 weeks without adhesion to the surrounding tissues. Neither breakage of the PVA-H shield itself nor infection or degeneration in the surrounding tissue was observed 
Sungur111 2006 Chickens Application of bovine pericardia to injured flexor tendons in chicken toe Significantly less adhesion formation in the bovine pericardia treated group 
Ultrasound 
Maiti77 2006 Adult goats pulsed ultrasound therapy was started 3 days after repair of tendinous injury at an intensity of 1 W/cm(2) for 10 min daily for 10 consecutive days Air tenograms and ultrasonography examinations showed that there was a marked regression of peritendinous adhesion between the tendon and skin on day 30 post-tendon injury repaired. The tendon at the repair site attained near normal thickness and density 
    Adhesions were present in the repair site of superficial digital flexor tendon in all animals of the control group 
    Histopathologically, the granulation tissue was comparatively better organized at the healing site in the ultrasound-treated animals 
Turner78 1989 Cockerel Application of ultrasound The application of ultrasound to sutured cockerel tendons produced no change in the mechanical strength of the tendon at 6 weeks, or its propensity to form adhesions, relative to untreated control sutured tendons 

Hyaluronic acid

Mechanism of action and role in adhesion prevention

Hyaluronic acid (HA) is a polysaccharide found in synovial fluid. Although the exact mechanism of action in adhesion prevention is unknown, HA has been suggested to play a possible role during the early stages of healing of a variety of connective tissues, including injured tendon.49,50

Supporting evidence

Hyaluronic acid has been extensively studied as an adjunct to adhesion prevention in digits. Some investigations suggest that HA promotes tendon healing and decreases adhesion formation (Table 2), but some studies did not show beneficial effects.51

Human studies

To date, few studies have been carried out on human subjects. In a prospective double-blind, randomized, clinical study with open therapeutic control, sodium hyaluronate or physiological saline solution was injected into the tendon sheath after completion of tenorrhaphy or tendon grafting in 120 digits. Sodium hyaluronate had no statistically significant effect as evaluated on total active motion at follow-up.51 Another prospective, double-blind, randomized, controlled clinical trial52 to assess the use of ADCON-T/N (a glycosaminoglycan-rich substance similar to HA) after flexor tendon repair in zone II revealed no statistically significant effect on total active motion at 3, 6 and 12 months after ADCON-T/N therapy, Though there was no significant difference in the mean total active motion of the two groups, the ADCON group of patients took significantly less time (P = 0.02) to achieve the final TAM (10 weeks compared with 14 weeks in the control group). These studies do not demonstrate any significant benefit of HA in digital adhesion prevention in human trials.

5-Fluorouracil

Mechanism of action and role in adhesion prevention

Although the mechanism of the reduction in adhesion formation by 5-fluorouracil (5-FU) is not known, cell proliferation and the ability to contract a fibroblast-populated collagen lattice are inhibited within the synovial sheath.53

Exposure of fibroblasts to 5-FU causes reduction of extracellular matrix molecules and growth factor production.54 This suggests that 5-FU, by modulating cellular activity without preventing cell proliferation, could reduce adhesion formation without preventing wound healing.

Supporting evidence

The proliferative and inflammatory responses can be significantly reduced in tendons treated with 5-FU. There seems to be a reduction in the cellular cytokine response and in the activity of the known pro-scaring agent, transforming growth factor beta (TGF-β) 1.55 Also, breaking strength of tendons treated with 5-FU was not different from control groups.56 No human trials have been reported.

Human amniotic fluid

Mechanism of action and role in adhesion prevention

Human amniotic fluid (HAF) is rich in substances such as hormones, cytokines, polypeptide growth factors that influence cell proliferation and differentiation of cells.

Although the exact mechanism of amniotic fluid in adhesion prevention has yet to be elucidated, amniotic fluid may have some type of inhibitory effect on fibroblast proliferation.57

Supporting evidence

The least adhesion and the best healing were observed in tendons treated with HAF application when compared with control groups (Table 2).58 No human trials have been reported.

Transforming growth factor beta inhibitors

Mechanism of action and role in adhesion prevention

Transforming growth factor beta is a cytokine that plays multiple roles in wound healing but is also implicated in the pathogenesis of excessive scar formation.59 TGF-β stimulates chemotaxis, promotes angiogenesis and regulates a wide spectrum of matrix proteins.

Transforming growth factor beta accelerates the wound-healing process in several animal models. However, this effect may proceed uncontrollably and result in pathologic fibrosis, with excessive disordered collagen deposition resulting in tendon adhesions.60 Hence, inhibitors of TGF-β have been used to reduce adhesion formation.

Supporting evidence

Transforming growth factor beta inhibition using a neutralizing antibody was effective in blocking TGF-β-induced collagen I production in cultured flexor tendons.61

Also, intra-operative infiltration of neutralizing antibody to TGF-β1 improves flexor tendon excursion.

As TGF-β1 is thought to contribute to the pathogenesis of excessive scar formation, intra-operative biochemical modulation of TGF-β1 levels limits flexor tendon adhesion formation (Table 2).59 Mannose-6-phosphate is effective in reducing TGF-β up-regulated collagen production in an in vitro model, which improves the range of motion after flexor tendon repair.62 No human trials have been reported.

Combination therapy

Addition of other substances to HA augments the action of HA in decreasing adhesions. Several combinations have been tried, such as amniotic membrane, dipalmitoyl phosphatidylcholine, carboxymethylcellulose and NSAIDS (Table 2). No human trials have been reported.

Others

Several other chemical adjuvants have also been investigated for their potential role in adhesion prevention. These are alginate solution, collagen synthesis inhibitor (CPHI-I), enriched collagen solution, plant alkaloid halofuginone, human-derived fibrin sealant and topical beta-aminopropionitrile. No human trials have been reported. 63–65

Barriers

The cellular activity of intra-synovial flexor tendons may be specially adapted to intra-synovial environments. Therefore, reconstruction of damaged flexor tendon sheaths with a biocompatible, diffusible membrane may not interfere with the nutrition and healing of repaired flexor tendons. Furthermore, acting as a barrier between surrounding tissues and the repaired tendon, an interposed membrane may be able to further reduce the formation of adhesions.68 This concept has led to the development of several chemical barriers, which promise to reduce adhesion prevention in digital tendons.

Expanded polytetrafluoroethylene

Expanded polytetrafluoroethylene (e-PTFE) is a microporous synthetic material. It is biochemically stable, soft, with a smooth surface and a high tensile strength.68,69 e-PTFE has also been used for reconstruction of tendon sheath and pulleys with promising results,70 and to decrease the formation of restrictive adhesions. Fascia lata patch grafts and autogenous free sheaths have also been used. Microscopic examination has shown that the area of healing was better organized with less restrictive-appearing adhesions when the sheath defect was grafted.71 Tang et al.72 demonstrated that the diameter of the repaired sheath exerts a significant influence on flexor tendon function. Enlargement of the flexor sheath may provide an additional way to improve the function of repaired tendons. No human trials have been reported.

Other materials

Several other materials such as hydroxyapatite, HA membrane, polyvinyl alcohol hydrogel (PVA-H) and bovine pericardia have also been tested for their efficacy on adhesion prevention.73–75 No human trials have been reported.76

Other modalities

Other modalities such as ultrasound therapy and pulsed electromagnetic field have also been tried, but only in animals, with controversial results.77,78

Ultrasound therapy

Mechanism of action and role in adhesion prevention

Ultrasound consists of inaudible high-frequency mechanical vibrations. The sound waves are transmitted by propagation through molecular collision and vibration, with a progressive loss of the intensity of the energy during passage through the tissue (attenuation), due to absorption and dispersion or scattering of the wave.79

Ultrasound may interact with one or more components of inflammation, and produce earlier resolution of inflammation.80 Also, accelerated fibrinolysis,81,82 stimulation of macrophage-derived fibroblast mitogenic factors,83 heightened fibroblast recruitment,80 accelerated angiogenesis,84 increased matrix synthesis,85 more dense collagen fibrils86 and increased tissue tensile strength87–89 have all been demonstrated in vitro. Such findings form the basis for the use of ultrasound to promote and accelerate tendon healing, repair and adhesion prevention.

The non-thermal effects of ultrasound, including cavitation and acoustic microstreaming, may be more important in the management of soft tissue lesions and adhesion prevention than thermal effects.90

Acoustic microstreaming is the unidirectional movement of fluids along cell membranes, which occurs as a result of the mechanical pressure changes within the ultrasound field. Microstreaming may alter cell membrane structure, function and permeability.91 It has been suggested to stimulate tissue repair.90 Effects of cavitation and microstreaming in vitro include stimulation of fibroblast repair and collagen synthesis,92–94,95 tissue regeneration93 and bone healing.94

These actions of ultrasound may be used as the basis to explain the mechanism in tendon adhesion prevention.

Supporting evidence

There was a marked regression of peritendinous adhesion between the tendon and skin on Day 30 post-tendon injury and the tendon at the reconstructive site attained near normal thickness and density.77 Treatment with ultrasound increased a range of movements, advanced scar maturation and decreased the amount of inflammatory infiltrate.78

Future therapies

Delivery of growth factor genes that may substantially increase the healing rate of injured digital tendons is a new application of gene therapy in the field of hand flexor tendon surgery. Adenoviral, adeno-associated viral and liposome-plasmid vectors have been used to deliver genes to tendons to improve its healing. These may well form part of future treatment modalities for adhesion prevention. However, at the present moment, clinical evidence is lacking.96,97

Conclusion

Both repair with scarring and regeneration can occur within the same animal, including man, and indeed within the same tissue, thereby suggesting that they share similar mechanisms and regulators.98 Consequently, by subtly altering the ratio of growth factors present during adult wound healing, one could induce adult wounds to heal with no scars, with accelerated healing and with no adverse effects. Several new surgical techniques and various pharmacological modalities have been proposed. However, most studies have been performed in animals, with very few human trials. The results of mobilization techniques are promising, but inconclusive regarding the most effective technique.

Poor methodological standards in animal studies mean that positive results rarely translate to the clinical domain,99 thus questioning whether these chemical adjuvants are really effective in humans. Also, when selecting an appropriate animal model, the major criteria to be considered are closely matched anatomic structure and the ease with which the treatment can be translated to a clinical setting. Adhesions formed after injury to the flexor tendon in primates have the closest resemblance to humans in both surgical technique and physical attributes. The use of rabbits, dogs and chickens, though interesting, may not be directly translatable to human clinical medicine, as their physical and anatomical features do not match the human anatomy.100–102

Therefore, the only thing that appears clinically justified in adhesion prevention is the need for early post-operative mobilization of digits after tendon injury or repair but the best method of mobilization remains controversial. Suggested changes in surgical techniques and various proposed pharmacological and non-pharmacological modalities need to withstand the test of adequately powered human trials before their potential benefit is accepted in routine clinical practice.

References

1
Gelberman
RH
Manske
PR
Factors influencing flexor tendon adhesions
Hand Clin
 , 
1985
, vol. 
1
 (pg. 
35
-
42
)
2
Jaibaji
M
Advances in the biology of zone II flexor tendon healing and adhesion formation
Ann Plast Surg
 , 
2000
, vol. 
45
 (pg. 
83
-
92
)
3
Wang
ED
Tendon repair
J Hand Ther
 , 
1998
, vol. 
11
 (pg. 
105
-
110
)
4
Manske
PR
Flexor tendon healing, (Review)
J Hand Surg [Br]
 , 
1988
, vol. 
13
 (pg. 
237
-
245
)
5
Manske
PR
Gelberman
RH
Vande Berg
JS
Lesker
PA
Intrinsic flexor-tendon repair. A morphological study in vitro
J Bone Joint Surg Am
 , 
1984
, vol. 
66
 (pg. 
385
-
396
)
6
Manske
PR
Lesker
PA
Histologic evidence of intrinsic flexor tendon repair in various experimental animals. An in vitro study
Clin Orthop Relat Res
 , 
1984
, vol. 
182
 (pg. 
297
-
304
)
7
Manske
PR
Lesker
PA
Biochemical evidence of flexor tendon participation in the repair process—an in vitro study
J Hand Surg [Br]
 , 
1984
, vol. 
9
 (pg. 
117
-
120
)
8
Mass
DP
Tuel
R
Human flexor tendon participation in the in vitro repair process
J Hand Surg [Am]
 , 
1989
, vol. 
14
 (pg. 
64
-
71
)
9
Mass
DP
Tuel
RJ
Intrinsic healing of the laceration site in human superficialis flexor tendons in vitro
J Hand Surg [Am]
 , 
1991
, vol. 
16
 (pg. 
24
-
30
)
10
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
, vol. 
7
 (pg. 
170
-
175
)
11
Matthews
P
Richards
H
Factors in the adherence of flexor tendon after repair. An experimental study in the rabbit
J Bone Joint Surg
 , 
1976
, vol. 
58B
 (pg. 
230
-
236
)
12
Siegler
AM
Kontopoulos
V
Wang
CF
Prevention of postoperative adhesions in rabbits with ibuprofen, a nonsteroidal anti-inflammatory agent
Fertil Steril
 , 
1980
, vol. 
34
 (pg. 
46
-
49
)
13
Strickland
JW
Development of flexor tendon surgery: twenty-five years of progress
J Hand Surg [Am]
 , 
2000
, vol. 
25A
 (pg. 
214
-
235
)
14
Barrie
KA
Wolfe
SW
Shean
C
Shenbagamurthi
D
Slade
JF
III
Panjabi
MM
A biomechanical comparison of multistrand flexor tendon repairs using an in situ testing model
J Hand Surg [Am]
 , 
2000
, vol. 
25-A
 (pg. 
499
-
506
)
15
Aoki
M
Manske
PR
Pruitt
DL
Larson
BJ
Work of flexion after tendon repair with various suture methods. A human cadaveric study
J Hand Surg [Br]
 , 
1995
, vol. 
20B
 (pg. 
310
-
313
)
16
Zhao
C
Amadio
PC
Momose
T
Couvreur
P
Zobitz
ME
An
KN
The effect of suture technique on adhesion formation after flexor tendon repair for partial lacerations in a canine model
J Trauma
 , 
2001
, vol. 
51
 (pg. 
917
-
921
)
17
Strick
MJ
Filan
SL
Hile
M
McKenzie
C
Walsh
WR
Tonkin
MA
Adhesion formation after flexor tendon repair: a histologic and biomechanical comparison of 2- and 4-strand repairs in a chicken model
J Hand Surg [Am]
 , 
2004
, vol. 
29A
 (pg. 
15
-
21
)
18
Dinopoulos
HT
Boyer
MI
Burns
ME
Gelberman
RH
Silva
MJ
The resistance of a four- and eight-strand suture technique to gap formation during tensile testing: an experimental study of repaired canine flexor tendons after 10 days of in vivo healing
J Hand Surg [Am]
 , 
2000
, vol. 
25A
 (pg. 
489
-
498
)
19
Gill
RS
Lim
BH
Shatford
RA
Toth
E
Voor
MJ
Tsai
TM
A comparative analysis of the six-strand double-loop flexor tendon repair and three other techniques: a human cadaveric study
J Hand Surg [Am]
 , 
1999
, vol. 
24A
 (pg. 
1315
-
1322
)
20
Thurman
RT
Trumble
TE
Hanel
DP
Tencer
AF
Kiser
PK
Two-, four-, and six-strand zone II flexor tendon repairs: an in situ biomechanical comparison using a cadaver model
J Hand Surg [Am]
 , 
1998
, vol. 
23A
 (pg. 
261
-
265
)
21
Matthews
R
Richards
H
The repair potential of digital flexor tendons
J Bone Joint Surg Br
 , 
1974
, vol. 
56B
 (pg. 
618
-
625
)
22
Lundborg
G
Experimental flexor tendon healing without adhesion formation: a new concept of tendon nutrition and intrinsic healing mechanisms
Hand
 , 
1976
, vol. 
8
 (pg. 
235
-
238
)
23
Lundborg
G
Rank
F
Experimental intrinsic healing of flexor tendon based upon synovial fluid nutrition
J Hand Surg [Am]
 , 
1978
, vol. 
3A
 (pg. 
21
-
31
)
24
Matthews
R
The fate of isolated segments of flexor tendons within the digital sheath
Br J Plast Surg
 , 
1976
, vol. 
29
 (pg. 
216
-
224
)
25
Manske
PR
Bridwell
K
Lesker
PA
Nutrient pathways to flexor tendons of chickens using tritiated proline
J Hand Surg [Am]
 , 
1978
, vol. 
3A
 (pg. 
352
-
357
)
26
Manske
PR
Whiteside
LA
Lesker
PA
Nutrient pathways to flexor tendons using hydrogen washout technique
J Hand Surg [Am]
 , 
1978
, vol. 
3A
 (pg. 
32
-
36
)
27
Lundborg
G
Holm
S
Myrhage
R
The role of the synovial fluid and tendon sheath for flexor tendon nutrition
Scand J Plast Reconstr Surg
 , 
1980
, vol. 
14
 (pg. 
99
-
107
)
28
Manske
PR
Lesker
PA
Nutrient pathways of flexor tendons in primates
J Hand Surg [Am]
 , 
1982
, vol. 
7A
 (pg. 
436
-
444
)
29
Manske
PR
Lesker
PA
Comparative nutrient pathways to the flexor profundus tendon in zone II of various experimental animals
J Surg Res
 , 
1983
, vol. 
34
 (pg. 
83
-
93
)
30
Gelberman
RH
VandeBerg
JS
Lundborg
GN
Akeson
WH
Flexor tendon healing and restoration of the gliding surface: an ultrastructural study in dogs
J Bone Joint Surg Am
 , 
1983
, vol. 
65A
 (pg. 
70
-
80
)
31
Strauch
B
de Moura
W
Ferder
M
Hall
C
Sagi
A
Greenstein
B
The fate of tendon healing after restoration of the integrity of the tendon sheath with autogenous vein grafts
J Hand Surg [Am]
 , 
1985
, vol. 
10A
 (pg. 
790
-
795
)
32
Peterson
WW
Manske
PR
Kain
CC
Lesker
PA
Effect of flexor sheath integrity on tendon gliding: a biomechanical and histologic study
J Orthop Res
 , 
1986
, vol. 
4
 (pg. 
458
-
465
)
33
Saldana
MJ
Ho
PK
Lichtman
DM
Chow
JA
Dovelle
S
Thomes
LJ
Flexor tendon repair and rehabilitation in zone II: open sheath technique versus closed sheath technique
J Hand Surg [Am]
 , 
1987
, vol. 
12A
 (pg. 
1110
-
1114
)
34
Gelberman
RH
Woo
SL-Y
Amiel
D
Horibe
S
Lee
D
Influences of flexor sheath continuity and early motion on tendon healing in dogs
J Hand Surg [Am]
 , 
1990
, vol. 
15A
 (pg. 
69
-
77
)
35
Peterson
WW
Manske
PR
Dunlap
J
Horwitz
DS
Kahn
B
Effect of various methods of restoring flexor sheath integrity on the formation of adhesions after tendon surgery
J Hand Surg [Am]
 , 
1990
, vol. 
15A
 (pg. 
48
-
56
)
36
Tang
JB
Ishii
S
Usui
M
Yamamura
T
Flexor sheath closure during delayed primary tendon repair
J Hand Surg [Am]
 , 
1994
, vol. 
19A
 (pg. 
636
-
640
)
37
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
, vol. 
5A
 (pg. 
537
-
543
)
38
Wilson
K
Moore
MJ
Rayner
CR
Fenton
OM
Extensor tendon repair: an animal model which allows immediate post-operative mobilisation
J Hand Surg [Br]
 , 
1990
, vol. 
15B
 (pg. 
74
-
78
)
39
Adolfsson
L
Soderberg
G
Larsson
M
Karlander
LE
The effects of a shortened postoperative mobilization programme after flexor tendon repair in zone 2
J Hand Surg [Br]
 , 
1996
, vol. 
21B
 (pg. 
67
-
71
)
40
Gelberman
RH
Nunley
JA
III
Osterman
AL
Breen
TF
Dimick
MP
Woo
SL
Influences of the protected passive mobilization interval on flexor tendon healing. A prospective randomized clinical study
Clin Orthop
 , 
1991
, vol. 
264
 (pg. 
189
-
196
)
41
Percival
NJ
Sykes
PJ
Flexor pollicis longus tendon repair: a comparison between dynamic and static splintage
J Hand Surg [Br]
 , 
1989
, vol. 
14B
 (pg. 
412
-
415
)
42
Hagberg
L
Abrahamsson
S
Philstrom
S
Carlsson
I
Active flexion versus rubber band traction for early controlled mobilization following flexor tendon repair in zone II. A controlled clinical study
J Hand Surg [Br]
 , 
2000
, vol. 
25B
 
Suppl 1
pg. 
52
 
43
Kneafsey
B
O'shaughnessy
M
Vidal
P
Milling
MA
Sykes
PJ
Controlled mobilization after flexor tendon repair: a prospective comparison of two methods
J Hand Surg [Br]
 , 
1994
, vol. 
19
 
Suppl 1
(pg. 
37
-
38
)
44
Scavenius
M
Soe-Nielsen
N
Boeckstyns
M
Sassene
I
Early active versus early passive mobilization regimen after primary tendon repair: a prospective randomized study [abstract]
2000
Danish Orthopaedic Society Autumn Meeting
26–27 October
Copenhagen, Denmark
45
Tang
JB
Xie
RG
Cao
Y
Ke
ZS
Xu
Y
A2 pulley incision or one slip of the superficialis improves flexor tendon repairs
Clin Orthop Res
 , 
2007
, vol. 
456
 (pg. 
121
-
127
)
46
Tang
JB
Flexor tendon repair in zone 2C
J Hand Surg [Br]
 , 
1994
, vol. 
19
 (pg. 
72
-
75
)
47
Kulick
MI
Brazlow
R
Smith
S
Hentz
VR
Injectable ibuprofen: preliminary evaluation of its ability to decrease pretendinous adhesions
Ann Plast Surg
 , 
1984
, vol. 
13
 (pg. 
459
-
467
)
48
Nishimura
K
Shimanuki
T
deZerega
GS
Ibuprofen in the prevention of experimentally induced post operative adhesions
Am J Med
 , 
1984
, vol. 
77
 (pg. 
102
-
106
)
49
St Onge
R
Weiss
C
Denlinger
JL
Balazs
EA
A preliminary assessment of Na-hyaluronate injection into “no man's land” for primary flexor tendon repair
Clin Orthop Relat Res
 , 
1980
, vol. 
146
 (pg. 
269
-
275
)
50
Thomas
SC
Jones
LC
Hungerford
DS
Hyaluronic acid and its effect on postoperative adhesions in the rabbit flexor tendon: a preliminary look
Clin Orthop
 , 
1986
, vol. 
206
 (pg. 
281
-
289
)
51
Hagberg
L
Exogenous hyaluronate as an adjunct in the prevention of adhesions after flexor tendon surgery: a controlled clinical trial
J Hand Surg [Am]
 , 
1992
, vol. 
17A
 (pg. 
132
-
136
)
52
Golash
A
Kay
A
Warner
JG
Peck
F
Watson
JS
Lees
VC
Efficacy of adcon-T/N after primary flexor tendon repair in zone II: a controled clinical trial
J Hand Surg
 , 
2003
, vol. 
28
 (pg. 
113
-
115
)
53
Akali
A
Khan
U
Khaw
PT
McGrouther
AD
Decrease in adhesion formation by a single application of 5-fluorouracil after flexor tendon injury
Plast Reconstr Surg
 , 
1999
, vol. 
103
 (pg. 
151
-
158
)
54
Occleston
NL
Daniels
JT
Tarnuzzer
RW
, et al.  . 
Single exposures to antiproliferatives. Long-term effects on ocular fibroblasts wound-healing behaviour
Invest Ophthalmol Vis Sci
 , 
1997
, vol. 
38
 (pg. 
1998
-
2007
)
55
Khan
U
Kakar
S
Akali
A
Bentley
G
McGrouther
DA
Modulation of the formation of adhesions during the healing of injured tendons
J Bone Joint Surg Br
 , 
2000
, vol. 
82
 (pg. 
1054
-
1058
)
56
Cerovac
S
Afoke
A
Akali
A
McGrouther
DA
Early breaking strength of repaired flexor tendon treated with 5-fluorouracil
J Hand Surg [Br]
 , 
2001
, vol. 
26B
 (pg. 
220
-
223
)
57
Kostecká
Z
Sobeková
A
Blahovec
J
Influence of ruminant amniotic fluid fractions on fibroblast and lymphocyte proliferation
Acta Vet Brno
 , 
2006
, vol. 
75
 (pg. 
169
-
174
)
58
Ozgenel
GY
Samli
B
Ozcan
M
Effects of human amniotic fluid on peritendinous adhesion formation and tendon healing after flexor tendon surgery in rabbits
J Hand Surg [Am]
 , 
2001
, vol. 
26
 (pg. 
332
-
339
)
59
Chang
J
Thunder
R
Most
D
Longaker
MT
Lineaweaver
WC
Studies in flexor tendon wound healing: neutralizing antibody to TGF-beta1 increases postoperative range of motion
Plast Reconstr Surg
 , 
2000
, vol. 
105
 (pg. 
148
-
155
)
60
Pierce
GF
Mustoe
TA
Lingelbach
J
, et al.  . 
Transforming growth factor β reverses the glucocorticoid-induced wound-healing deficit in rats: possible regulation in macrophages by platelet-derived growth factor
Proc Natl Acad Sci USA
 , 
1989
, vol. 
86
 pg. 
2229
 
61
Zhang
AY
Pham
H
Ho
F
Teng
K
Longaker
MT
Chang
J
Inhibition of TGF-beta-induced collagen production in rabbit flexor tendons
J Hand Surg [Am]
 , 
2004
, vol. 
29
 (pg. 
230
-
235
)
62
Bates
SJ
Morrow
E
Zhang
AY
Pham
H
Longaker
MT
Chang
J
Mannose-6-phosphate, an inhibitor of transforming growth factor-beta, improves range of motion after flexor tendon repair
J Bone Joint Surg Am
 , 
2006
, vol. 
88
 (pg. 
2465
-
2467
)
63
Namba
J
Shimada
K
Saito
M
Murase
T
Yamada
H
Yoshikawa
H
Modulation of peritendinous adhesion formation by alginate solution in a rabbit flexor tendon model
J Biomed Mater Res B Appl Biomater
 , 
2007
, vol. 
80
 (pg. 
273
-
279
)
64
McCombe
D
Kubicki
M
Witschi
C
Williams
J
Thompson
EW
A collagen prolyl 4-hydroxylase inhibitor reduces adhesions after tendon injury
Clin Orthop
 , 
2006
, vol. 
451
 (pg. 
251
-
256
)
65
Jones
ME
Burnett
S
Southgate
A
Sibbons
P
Grobbelaar
AO
Green
CJ
The role of human-derived fibrin sealant in the reduction of postoperative flexor tendon adhesion formation in rabbits
J Hand Surg [Br]
 , 
2002
, vol. 
27B
 (pg. 
78
-
82
)
66
Nyska
M
Nyska
A
Rivlin
E
, et al.  . 
Topically applied halofuginone, an inhibitor of collagen type I transcription, reduces peritendinous fibrous adhesions following surgery
Connect Tissue Res
 , 
1996
, vol. 
34
 (pg. 
97
-
103
)
67
Speer
DP
Feldman
S
Chvapil
M
The control of peritendinous adhesions using topical beta-aminopropionitrile base
J Surg Res
 , 
1985
, vol. 
38
 (pg. 
252
-
257
)
68
Hanff
G
Abrahamsson
SO
Matrix synthesis and cell proliferation in repaired flexor tendons within E-PTFE reconstructed flexor tendon sheaths
J Hand Surg
 , 
1996
, vol. 
21
 (pg. 
642
-
646
)
69
Porat
S
Rousso
M
Shoshan
S
Improvement of gliding function of flexor tendons by topically applied enriched collagen solution
J Bone Joint Surg Br
 , 
1980
, vol. 
62B
 (pg. 
208
-
213
)
70
Hanff
G
Abrahamsson
SO
Cellular activity in e-PTFE reconstructed pulleys and adjacent regions of deep flexor tendons: an experimental biochemical study in rabbits
J Hand Surg
 , 
1996
, vol. 
21
 (pg. 
419
-
423
)
71
Kessler
FB
Epstein
MJ
Lannik
D
Maher
D
Pappus
S
Facia patch graft for a digital flexor sheath defect over primary tendon repair in the chicken
J Hand Surg [Am]
 , 
1986
, vol. 
11
 (pg. 
241
-
245
)
72
Tang
JB
Shi
D
Zhang
QG
Biochemical and histological evaluation of tendon sheath management
J Hand Surg [Am]
 , 
1996
, vol. 
21
 (pg. 
900
-
908
)
73
Hanff
G
Hagberg
L
Prevention of restrictive adhesions with expanded polytetrafluoroethylene diffusible membrane following flexor tendon repair: an experimental study in rabbits
J Hand Surg [Am]
 , 
1998
, vol. 
23A
 (pg. 
658
-
664
)
74
Siddiqi
NA
Hamada
Y
Yamaguchi
T
Toshima
T
An experimental study on the application of a hydroxyapatite artificial tendon sheath to prevent adhesions after tendon repair (Part 1)
Nippon Seikeigeka Gakkai Zasshi
 , 
1991
, vol. 
65
 (pg. 
561
-
570
)
75
Siddiqi
NA
Hamada
Y
Ide
T
Akamatsu
N
Effects of hydroxyapatite and alumina sheaths on postoperative peritendinous adhesions in chickens
J Appl Biomater
 , 
1995
, vol. 
6
 (pg. 
43
-
53
)
76
Kobayashi
M
Toguchida
J
Oka
M
Development of polyvinyl alcohol-hydrogel (PVA-H) shields with a high water content for tendon injury repair
J Hand Surg [Br]
 , 
2001
, vol. 
26-B
 (pg. 
436
-
440
)
77
Maiti
SK
Kumar
N
Singh
GR
Hoque
M
Singh
R
Ultrasound therapy in tendinous injury healing in goats
J Vet Med A Physiol Pathol Clin Med
 , 
2006
, vol. 
53
 (pg. 
249
-
258
)
78
Turner
SM
Powell
ES
Ng
CS
The effect of ultrasound on the healing of repaired cockerel tendon: is collagen cross-linkage a factor?
J Hand Surg [Br]
 , 
1989
, vol. 
14
 (pg. 
428
-
433
)
79
ter Haar
C
Basic physics of therapeutic ultrasound
Physiotherapy
 , 
1987
, vol. 
73
 (pg. 
110
-
113
)
80
Young
SR
Dyson
M
Effect of therapeutic ultrasound on the healing of full-thickness excised skin lesions
Ultrasonics
 , 
1990
, vol. 
28
 (pg. 
175
-
180
)
81
Harpaz
D
Chen
X
Francis
CW
, et al.  . 
Ultrasound enhancement of thrombolysis and reperfusion in vitro
J Am Coll Cardiol
 , 
1993
, vol. 
2
 (pg. 
1507
-
1511
)
82
Francis
CW
Onundarson
PT
Cartensen
EL
, et al.  . 
Enhancement of fibrinolysis by ultrasound
J Clin Invest
 , 
1992
, vol. 
90
 (pg. 
2063
-
2068
)
83
Young
SR
Dyson
M
Macrophage responsiveness to therapeutic ultrasound
Ultrasound Med Biol
 , 
1990
, vol. 
16
 (pg. 
809
-
816
)
84
Young
SR
Dyson
M
The effect of therapeutic ultrasound on angiogenesis
Ultrasound Med Biol
 , 
1990
, vol. 
16
 (pg. 
61
-
69
)
85
Webster
DF
The effect of ultrasound on wound healing
1980
London
University of London
 
PhD thesis
86
Friedar
S
A pilot study: the therapeutic effect of ultrasound following partial rupture of Achilles tendons in male rats
J Orthop Sports Phys Ther
 , 
1988
, vol. 
10
 pg. 
39
 
87
Byl
NN
McKenzie
AL
West
JM
, et al.  . 
Low dose ultrasound effect on wound healing: a controlled study with Yucatan pigs
Arch Phys Med Rehab
 , 
1992
, vol. 
73
 (pg. 
656
-
664
)
88
Byl
NN
McKenzie
AL
Wong
T
, et al.  . 
Incisional wound healing: a controlled study of low and high dose ultrasound
J Orth Sports Phys Ther
 , 
1993
, vol. 
18
 (pg. 
619
-
628
)
89
Pocock
BJZ
The effect of therapeutic ultrasound on the mechanical properties of surgical incisions in Wistar rats
1994
London
University of London
 
BSc thesis
90
Dyson
M
Suckling
J
Stimulation of tissue repair by ultrasound: a survey of the mechanisms involved
Physiotherapy
 , 
1978
, vol. 
64
 (pg. 
105
-
108
)
91
Williams
AR
Production and transmission of ultrasound
Physiotherapy
 , 
1987
, vol. 
73
 (pg. 
113
-
116
)
92
Webster
DF
Harvey
W
Dyson
M
Pond
JB
The role of ultrasound-induced cavitation in the ‘in vitro’ stimulation of collagen synthesis in human fibroblasts
Ultrasonics
 , 
1980
, vol. 
18
 (pg. 
33
-
37
)
93
Dyson
M
Luke
DA
Induction of mast cell degranulation in skin by ultrasound
IEEE Trans Ultrason Ferroelectr Freq Control
 , 
1986
pg. 
194
  
UFFC 33
94
Pilla
AA
Figueiredo
M
Nasser
P
, et al.  . 
Non-invasive low intensity pulsed ultrasound: a potent accelerator of bone repair
1990
Proceedings, 36th Annual Meeting, Orthopaedics Research Society
95
Gan
BS
Huys
S
Sherebrin
MH
Scilley
CG
The effects of ultrasound treatment on flexor tendon healing in the chicken limb
J Hand Surg [Br]
 , 
1995
, vol. 
20
 (pg. 
809
-
814
)
96
Zhu
B
Cao
Y
Xin
KQ
, et al.  . 
Tissue reactions of adenoviral, adeno-associated viral, and liposome-plasmid vectors in tendons and comparison with early-stage healing responses of injured flexor tendons
J Hand Surg [Am]
 , 
2006
, vol. 
31B
 (pg. 
1652
-
1660
)
97
Tang
JB
Cao
Y
Zhu
B
Xin
KQ
Wang
XT
Liu
PY
Adeno-associated virus-2 ediated bFGF gene transfer to digital flexor tendons significantly increases healing strength. An in vivo study
J Bone Joint Surg Am
 , 
2008
, vol. 
90A
 (pg. 
1078
-
1089
)
98
Ferguson
MW
O'Kane
S
Scar-free healing: from embryonic mechanisms to adult therapeutic intervention
Philos Trans R Soc Lond B Biol Sci
 , 
2004
, vol. 
29
 (pg. 
839
-
850
)
99
Hackam
DG
Translating animal research into clinical benefit
Br Med J
 , 
2007
, vol. 
27
 (pg. 
163
-
164
)
100
Carpenter
JE
Thomopoulos
S
Soslowsky
LJ
Animal models of tendon and ligament injuries for tissue engineering applications
Clin Orthop Relat Res
 , 
1999
, vol. 
367
 (pg. 
S296
-
S311
)
101
Smith
AM
Forder
JA
Annapureddy
SR
Reddy
KS
Amis
AA
The porcine forelimb as a model for human flexor tendon surgery
J Hand Surg [Br]
 , 
2005
, vol. 
30B
 (pg. 
307
-
309
)
102
Pruzansky
ME
A primate model for the evaluation of tendon adhesions
J Surg Res
 , 
1987
, vol. 
42
 (pg. 
273
-
276
)
103
Tanaka
T
Zhao
C
Sun
YL
Zobitz
ME
An
KN
Amadio
PC
The effect of carbodiimide-derivatized hyaluronic acid and gelatin surface modification on peroneus longus tendon graft in a short-term canine model in vivo
J Hand Surg [Am]
 , 
2007
, vol. 
32A
 (pg. 
876
-
881
)
104
Zhao
C
Sun
YL
Amadio
PC
Tanaka
T
Ettema
AM
An
KN
Surface treatment of flexor tendon autografts with carbodiimide-derivatized hyaluronic Acid. An in vivo canine model
J Bone Joint Surg Am
 , 
2006
, vol. 
88A
 (pg. 
2181
-
2191
)
105
Akasaka
T
Nishida
J
Araki
S
Shimamura
T
Amadio
PC
An
KN
Hyaluronic acid diminishes the resistance to excursion after flexor tendon repair: an in vitro biomechanical study
J Biomech
 , 
2005
, vol. 
38
 (pg. 
503
-
507
)
106
Kulick
MI
Smith
S
Hadler
K
Oral ibuprofen: evaluation of its effect on peritendinous adhesions and the breaking strength of a tenorrhaphy
J Hand Surg [Am]
 , 
1986
, vol. 
11A
 (pg. 
110
-
120
)
107
Szabo
RM
Younger
E
Effects of indomethacin on adhesion formation after repair of zone II tendon lacerations in the rabbit
J Hand Surg [Am]
 , 
1990
, vol. 
15A
 (pg. 
480
-
483
)
108
Moran
SL
Ryan
CK
Orlando
GS
Pratt
CE
Michalko
KB
Effects of 5-fluorouracil on flexor tendon repair
J Hand Surg [Am]
 , 
2000
, vol. 
25A
 (pg. 
242
-
251
)
109
Işik
S
Oztürk
S
Gürses
S
, et al.  . 
Prevention of restrictive adhesions in primary tendon repair by HA-membrane: experimental research in chickens
Br J Plast Surg
 , 
1999
, vol. 
52
 (pg. 
373
-
379
)
110
Karakurum
G
Buyukbebeci
O
Kalender
M
Gulec
A
Seprafilm interposition for preventing adhesion formation after tenolysis. An experimental study on the chicken flexor tendons
J Surg Res
 , 
2003
, vol. 
113
 (pg. 
195
-
200
)
111
Sungur
N
Uysal
A
Koçer
U
, et al.  . 
Prevention of tendon adhesions by the reconstruction of the tendon sheath with solvent dehydrated bovine pericard: an experimental study
J Trauma
 , 
2006
, vol. 
61
 (pg. 
1467
-
1472
)
112
Rothkopf
DM
Jr
Webb
S
Szabo
RM
Gelberman
RH
May
JW
Jr
An experimental model for the study of canine flexor tendon adhesions
J Hand Surg [Am]
 , 
1991
, vol. 
16A
 (pg. 
694
-
700
)
113
Noguchi
M
Seiler
JG
III
Gelberman
RH
Sofranko
RA
Woo
SL-Y
In vitro biomechanical analysis of suture methods for flexor tendon repair
J Orthop Res
 , 
1993
, vol. 
11
 (pg. 
603
-
611
)
114
Gaillard
GC
Merrilees
MJ
Bell-Booth
PG
Reilly
HC
Flint
MH
The proteoglycan content and the axial periodicity of collagen and tendon
Biochem J
 , 
1977
, vol. 
163
 pg. 
145
 
115
Sungur
N
Uysal
A
Koçer
U
Karaaslan
O
Gümüş
M
Sökmensüer
LK
Sökmensüer
C
Prevention of tendon adhesions by the reconstruction of the tendon sheath with solvent dehydrated bovine pericard: An experimental study
J Trauma
 , 
2006
, vol. 
61
 (pg. 
1467
-
1472
)
116
Zhao
C
Amadio
PC
Momose
T
Couvreur
P
Zobitz
ME
An
KN
The effect of suture technique on adhesion formation after flexor tendon repair for partial lacerations in a canine model
J Trauma
 , 
2001
, vol. 
51
 (pg. 
917
-
921
)
117
Dinopoulos
HT
Boyer
MI
Burns
ME
Gelberman
RH
Silva
MJ
The resistance of a four- and eight-strand suture technique to gap formation during tensile testing: an experimental study of repaired canine flexor tendons after 10 days of in vivo healing
J Hand Surg [Am]
 , 
2000
, vol. 
25A
 (pg. 
489
-
498
)