Flexor tendon injury: advances in repair and biology

Steve K. Lee and Ashok Dubey

Purpose of review
Flexor tendon injuries of the hand continue to be a
challenging problem. This is a review of the latest advances
in flexor tendon injuries and their treatment.
Recent findings
Advances have been in two major areas: flexor tendon repair
technique and biological advances. Bone suture-anchor
repair methods for zone I flexor tendon injuries have shown
increased strength, decreased gapping, and the avoidance
of button complications. For zone II injuries, a new
combination repair method of a cross-locked cruciate core
suture and interlocking horizontal mattress circumferential
suture has superior strength with minimal increase in work
of flexion. The major areas of biological research are cellular
research and tissue engineering, molecular medicine, gene
therapy, and pulsed electromagnetic field therapy.
Summary
New flexor tendon repair methods have the advantage of
increased strength to allow for early active range of motion
with minimal gapping and minimal increase in work of flexion
to allow for smooth tendon gliding. Advances in biological
medicine may augment tendon repair strength while
decreasing adhesions.
Keywords
flexor tendon repair, hand, molecular medicine, tissue
engineering
Curr Opin Orthop 18:339346. 2007 Lippincott Williams & Wilkins.
NYU Hospital for Joint Diseases Orthopaedic Institute, New York, New York, USA
Correspondence to Steve K. Lee, MD, NYU Hospital for Joint Diseases
Orthopaedic Institute, 301 East 17th Street, Suite 413, New York, NY 10003, USA
Tel: +1 212 598 6697; fax: +1 212 598 6560; e-mail: Steve.Lee@nyumc.org
Current Opinion in Orthopaedics 2007, 18:339346
Abbreviation
bFGF

basic fibroblast growth factor

2007 Lippincott Williams & Wilkins

1041-9918

Introduction
In the past 50 years there have been significant advances
in the treatment of flexor tendon injuries. Until the 1960s,
Bunnells [1] concept of no mans land was universally
accepted and reconstruction of zone II flexor tendon
injuries with tendon grafts was performed rather than
primary repair. During the 1960s, several reports by
authors such as Verdan [2,3], Kleinert et al. [4] and Kessler
and Nissim [5] refuted the concept that zone II flexor
tendon injuries should not be repaired primarily. The
current flexor tendon injury areas of interest include
methods of repair and the use of biological science to
improve the outcomes of the treatment of flexor
tendon injury.

Flexor tendon repair

The major updates detailed here regarding repair
methods will involve injuries in zone I, injuries in
zone II, adhesion reduction, and others.
Zone I

For zone I injuries where there is inadequate distal

tendon length for tendon to tendon repair and advancement of the flexor digitorum profundus will be less than
1 cm, tendon repair to the distal phalanx is the standard
treatment. The use of bone suture anchors for flexor
digitorum profundus repair to the distal phalanx may
supplant the original Bunnell pullout-button repair
method [6
] and its modifications [7]. When reviewed
critically, the outcome of the Bunnell suture button
method does not have universally good outcomes [8,9].
The main reason is that a nonlocking suture technique
with monofilament suture material necessary for pullout
allows for excessive gapping. In a cadaveric model of
button repair, Schreuder et al. [10
] showed that gap
formation after 500 cycles was greatest with Prolene
suture (6.8 mm) followed by Supramid suture (4.0 mm)
and was smallest for Ethibond suture (1.7 mm,
SD  1.7 mm; P < 0.05). These findings echo results
reported by Silva et al. [11] in a cadaveric button repair
model with 3-0 Prolene comparing Bunnell, Kessler, and
Kleinert. At 20 N, all groups produced gaps of greater
than 8 mm. Although not specifically tested for zone I,
gapping of greater than 23 mm is unacceptable for
tendon healing and gliding resistance in zone II [12,13].
Zone I repair with bone suture anchors where there is no
need for suture pullout allows for the use of a locking
suture method with a multifilament suture material that is
stronger and stiffer than monofilament suture materials.
339

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340 Hand and wrist

Other advantages of the suture-anchor technique is that it

is better tolerated by patients and it avoids the risks
associated with the pullout-button suture technique of
permanent nail deformity, skin necrosis from button
pressure, and rupture due to catching of the button on
objects [14
,1517].

Figure 2 (a) Volar and (b) lateral views showing avulsed flexor
digitorum profundus (FDP) tendon and surgical exposure, and
(c) volar and cross-sectional views showing suture-anchor
placement in the distal phalanx and suture technique

In a cadaveric model, Brustein et al. [18] compared the

button repair with 3-0 nylon, one mini Mitek two-strand
repair with the Bunnell suture pattern using 3-0 Ethibond, and two micro Miteks and four-strand modified
Becker suture with 3-0 Ethibonds. The two-micro-Mitek
technique was stronger (69.6 N) than the button (43.3 N)
and the single mini Mitek (44.6 N). No gap information
was obtained.
Schreuder et al. [14
] studied the effect of bone sutureanchor orientation (Fig. 1). The results of this study
showed that the 458 retrograde angle was superior, based
on the deadman theory originally introduced by
Burkhart [19]. This was a cadaveric biomechanical
model using three anchor angles, one micro Mitek
anchor, 3-0 Ethibond, and Bunnell suture method. Gapping with the 458 retrograde angle was 2.0 mm, for the
908 angle 4.7 mm, and for the 458 antegrade angle 5.0 mm.
Ultimate load to failure was 30 N for all groups, although
this model only used one micro Mitek anchor. In the 458
retrograde group, 100% failed by the suture cutting
through the anchor eyelet. For the other groups 33%
failed by anchor pullout [14
]. Other conclusions that we
extrapolate from this study are: more than one micro
Mitek anchor is required, and use of a stronger suture

Figure 1 Diagrammatic illustration of the mechanical testing

set-up and anchor orientation

From [6
].

material that does not cut through the anchor eyelet

should improve overall construct strength.
Further support comes from a clinical study by
McCallister et al. [6
] comparing the outcome of patients
treated with a modified pullout-button suture technique
with a suture anchor (Fig. 2). The suture-anchor group
returned to work significantly earlier. There were no
significant differences in active range of motion, grip
strength, sensibility, or flexion contracture.
In conclusion, we believe that zone I flexor tendon
injuries should be repaired with a four-strand lockingsuture method with multifilament suture material and
two micro Mitek anchors placed in a 458 retrograde
fashion. We are currently investigating improved repair
methods which use better suture materials that are less
likely to fail at the anchor junction and stronger, stiffer,
and more practical suture techniques.
Zone II

Originally called no-mans land by Bunnell, flexor tendon repair in zone II is now commonplace, although the
ability to achieve predictably excellent results remains
elusive. Recent research is in the areas of repair method
and materials and adhesion reduction.
Repair method and materials

From [13].

The best method of zone II repairs is controversial.

Virtually every center has its own method of repair. Osada
et al. [20
] reported good results with a six-strand flexor
tendon suture technique followed by controlled active

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Flexor tendon injury Lee and Dubey 341

Figure 3 Schematic diagram of the Teno Fix device

Figure 4 The cross-locked cruciate (CLC) core suture method

From: Su BW, Solomons M, Barrow A, et al. A device for zone-II flexor

tendon repair. J Bone Joint Surg Am 2006. 88 (suppl 1):3749.

mobilization. In a randomized prospective study, Su et al.

[21] compared the results of treatment of zone II flexor
tendon injuries using a new tendon repair device (Teno
Fix; Ortheon Medical, Winter Park, Florida, USA; Fig. 3)
to perform a four-strand cruciate repair. There were
significantly fewer tendon ruptures in the Teno Fix repair
group than in the cruciate repair group. There were,
however, no differences between the two groups in terms
of range of motion, DASH score, pinch and grip strength,
pain, swelling, or neurologic recovery. Although functional outcomes between the two groups in this study are
similar, the use of the Teno Fix device requires both an
adequate surgical exposure as well as tendons of adequate
size to accommodate the device [21]. In a later study,
Su et al. [22
] reported the histological findings after dog
flexor tendon repair with the Teno Fix device. Only
seven out of the 16 dogs in this study had a successful
repair because of difficulties with cast immobilization. Six
out of the seven remaining dogs demonstrated no gapping at the repair site [22
]. Histological analysis of the
seven tendon repairs showed minimal or no adhesions as
well as a mild inflammatory response within the tendon.
The authors of these studies have shown that the Teno
Fix device is effective with minimal tendon adhesion or
inflammation when used in the appropriate setting. Cost
of the device and the need for wide exposure may be
disadvantages of this repair method.
Matheson et al. [23] compared the biomechanical properties of three methods of repair (modified Kessler core
suture with a running epitenon suture, a modified Kessler
core suture with a cross-stitched epitenon suture, and a
four-strand Savage core suture with a running epitenon
suture) that underwent cyclical loading. The results of
this study showed that the Savage repair method was both
significantly stiffer and had significantly less gapping than
the two Kessler repair methods. There were no significant differences between the two Kessler methods with
respect to stiffness or gap formation.
The optimal repair method should be strong enough to
allow for an early active motion protocol without gapping

and minimal increase in work of flexion. A new repair

method of cross-locked cruciate core suture [24] with 3-0
Fiberwire [25], and circumferential suture of interlocking
horizontal mattress (IHM) [26] combines the best
methods and materials for core suture technique, suture
material, and circumferential suture technique.
Popularized by Wolfe and colleagues [2731], the cruciate repair method appears to come closest to the ideal
suture technique according to Strickland [32]. Croog
et al. [24] studied the various locked cruciate methods
and concluded that the cross locked cruciate had the
highest 2 mm gap force and ultimate load to failure
(Fig. 4). The cross-locked cruciate suture method is
admittedly more technically challenging than Kesslertype methods, but we feel that the benefits far outweigh
the technical learning curve. Surgical experience in
the laboratory (porcine tendons are an excellent, costeffective training tool) is highly beneficial before using
this method clinically. There are pearls and pitfalls to the
cross-locked cruciate. First, tendon ends must be perfectly opposed before suturing; we prefer to hold tendon
ends with 25 g needles. Once the second locked cruciate
is placed, the tendon ends cannot be slid closer together
or farther apart. A major benefit of the cross-locked
cruciate is that it does not bunch or trumpet the tendon
ends, thereby decreasing bulk and minimizing increase in
work of flexion. Second, start suturing centrally and
dorsally. Dorsal placement produces a stronger repair
[33] and is less likely to allow the suture knot to trigger
on pulleys.
Lawrence and Davis [25] investigated the mechanical
properties of five nonabsorbable suture materials (monofilament nylon, monofilament polypropylene Prolene,
braided polyester Ethibond, stainless-steel wire, and
braided polyethylene Fiberwire) in a locking four-strand
flexor tendon repair configuration. They found that
Fiberwire (Arthrex, Naples, Florida, USA) and stainless
steel were the strongest and stiffest materials. In a
mechanical study to determine knot bulk and security,
Lee et al. [34] studied 3-0 Ethilon, Prolene, Ethibond,
and Fiberwire. Fiberwire had the lowest knot bulk and
highest knot security at six knots (surgeons knot plus five

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342 Hand and wrist

Figure 5 The interlocking horizontal mattress (IHM) circumferential suture method

Figure 7 Clinical intra-operative photograph of the cross-locked

cruciateinterlocking horizontal mattress (CLCIHM) combination repair method

square half-hitches). Based on these studies, we recommend six knots of 3-0 Fiberwire as the preferable
core suture.
For the circumferential suture, Dona et al. [26] studied
four groups: running, cross stitch (Silfverskiold), interlocking cross stitch, and interlocking horizontal mattress
in a sheep model with 6-0 Prolene and no core suture.
The interlocking horizontal mattress method had the
highest 2 mm gap force (26 N), stiffness, and ultimate
load to failure (53 N) [26] (Fig. 5).
Lee et al. [35] reported the superior biomechanical
characteristics of the cross-locked cruciateinterlocking
horizontal mattress (CLCIHM) combination repair and
we recently have confirmed superior strength (90 N 2 mm
gap force, 111 N load to failure) and low work of flexion
characteristics (5% increase in work of flexion; Goldstein
RY, Geldwert D, Terranova C et al., unpublished data) in
a cadaveric cyclically loading model (Fig. 6). We have had
early clinical success and this remains our repair method
of choice for zone II injuries (Figs 7 and 8).
Adhesions

Adhesions have always plagued flexor tendon repair and

have been the most common reason for loss of digital
motion [3638]. Ferguson and Rinker [39
] performed an
animal study to determine if a hydrogel sealant would
prevent adhesion formation in a chicken model. FocalSeal-L (Genzyme Corp., Cambridge, Massachusetts,

USA) is a synthetic surgical sealant used in thoracic

surgery. This sealant is painted on as a liquid on the
affected tissue and then sets without adhering to the
surrounding tissue. The results of this chicken flexor
tendon model revealed that there was decreased
peritendinous adhesion formation histologically and
decreased work of flexion in the group treated with
FocalSeal-L. There was no significant difference in
breaking strength of the repair. Hydrogel sealant application appears promising as it is easy to use, biocompatible, allows tendon motion, and does not add bulk to
the repair. Sungur et al. [40] also used a chicken model to
show that there was significantly less adhesion formation
when solvent-dehydrated bovine pericardium was used
for flexor sheath reconstruction as compared to the use of
autogenous fascia or leaving the sheath open.
Other advances

Cao et al. [41

] conducted a study comparing the

biomechanical properties of three different methods
(double-modified Kessler, locking cruciate, and modified
Savage) using two different lengths (10 and 4 mm) of core
suture purchase. The results of this study showed that all
three repair methods utilizing a core suture purchase of
10 mm had significantly higher initial gap force, higher
Figure 8 Three months after the cross-locked cruciateinterlocking horizontal mattress (CLCIHM) repair method has been
performed

Figure 6 The cross-locked cruciateinterlocking horizontal

mattress (CLCIHM) combination repair method

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Flexor tendon injury Lee and Dubey 343

2-mm gap force, and higher ultimate strength than those

repairs with 4-mm purchase.
Cao and Tang [42
] also conducted a study using a
chicken model that evaluated edema formation and flexor
tendon resistance to motion. The results of this study
showed that the force and work of flexion increased
progressively for the first 4 days and then leveled off
for the next 3 days. They recommended that postoperative motion should probably not be started immediately,
but rather between 4 and 7 days postoperatively.

Biological advances
Manipulation of biological aspects of tendon healing has
the potential to diminish the rate of adhesion formation
and increase the strength of the repair. Biological research
of tendon repair has taken place at the cellular, molecular
and genetic levels. Cellular research has focused on
mesenchymal stem cells and tissue engineering [43].
Mesenchymal stem cells are pluripotential cells that have
the ability to differentiate into various types of cells
including myocytes, chondrocytes, and tendon fibroblasts
[44]. Mesenchymal stem cells also produce extracellular
matrix and growth factors needed for tendon healing [43].
Tissue engineering is the process by which new tissues
are created in an ex-vivo environment. Efforts in tissue
engineering have focused on the use of scaffolds that
allow cells to grow that are easy to obtain, elicit minimal
immunogenic response, and are easily modulated by
local environmental factors [45
]. Molecular medical
approaches to improved tendon healing concentrate on
the growth factors, cytokines, and extracellular matrix
molecules that are involved in such processes as proteoglycan synthesis, blood vessel growth, and cell proliferation [43]. Gene therapy is the process by which newly
engineered genes are introduced into a host animal.

Cellular research and tissue engineering

Cellular research in flexor tendon injury is constantly
advancing. Mesenchymal stem cells have the potential
to augment flexor tendon repairs. Chong et al. [46
], using
an in-vivo rabbit model, compared the histological and
biomechanical properties of repaired Achilles tendon
lacerations treated with mesenchymal stem cells to a
control group. They showed that in the early part of healing
(3 weeks) the mesenchymal-stem-cell-treated group had
better-organized collagen fibers histologically and was
significantly stiffer than the control group. However, at
6 and 12 weeks there were no significant differences in
biomechanical properties between the two groups.
Although there have been several reported studies of invivo tendon engineering [4749], there are few studies
dealing with in-vitro tendon engineering [50]. Cao et al.
[51
] conducted an in-vitro tendon-engineering study
using hen tenocytes on a polyglycolic acid scaffold. This

study evaluated the effect of a constant strain on the

histological and biomechanical properties of engineered
tendons. The results of this study showed that tendon
could be engineered in vitro and that tendon exposed to
a constant tension had higher tensile strength and was
significantly thinner than the tendon that was not
exposed to tension.
The harvesting of autologous tenocytes results in a defect
at the donor site. Liu et al. [52
] conducted a study that
compared the use of dermal fibroblasts to tenocytes as a
source of cells for tendon engineering in a pig model with
a tendon defect. Histological and biomechanical analysis
of the tendon with the implanted cell-scaffold construct
showed that both fibroblast and tenocyte engineered
tendon had similar tensile strength and histology similar
to natural tendon at weeks 14 and 26. The use of dermal
fibroblasts may be a feasible alternative to the more
invasive harvest of tenocytes as a seed cell for tendon
engineering.

Molecular medicine
Tendon strength after repair can be influenced by molecular medicine. Hamada et al. [53
] conducted an in-vivo
rabbit study in which flexor tendon lacerations were
repaired with either plain nylon sutures or nylon sutures
coated with basic fibroblast growth factor (bFGF). The
results of this study showed that lacerations repaired with
the bFGF coated nylon sutures had a higher ultimate
strength and a greater fibroblastic response than lacerations repaired with plain nylon sutures. The use of growth
factors or modalities that augment production of such
factors has the potential to significantly increase the
strength of flexor tendon repairs.
Costa et al. [54
] conducted research to determine the
effect of individual growth factors (platelet-derived
growth factor-BB, insulin-like growth factor-1, and basic
fibroblast growth factor) on in-vitro growth of rabbit
flexor tendon synovial sheath cells, epitenon cells, and
endotenon cells. The results of this study showed that
proliferation of all cells increased in the presence of
individual growth factors and that there was a synergistic
effect of cell proliferation when these growth factors were
combined.
Control of adhesion formation through molecular medicine could significantly improve outcomes. McCombe
et al. [55
] reported on the results of use of an orally
administered collagen synthesis inhibitor (CPHI-I)
in a rat model with a crush injury of a flexor tendon.
They showed a significantly decreased work of flexion
(P < 0.05) in the treatment groups that received CPHI-I.
The rate of dermal collagen synthesis was also reduced
in the treatment group but did not have an impact on
wound healing.

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344 Hand and wrist

Reduction of excursion resistance with the use of

hyaluronic acid after tendon repair and grafting has been
investigated by Akasaka et al. [56,57
] in both dog and
human in-vitro models. The results of these studies
show diminished excursion resistance in both dog flexor
tendon repair models and human models using flexor
tendon grafts. Namba et al. [58] conducted a study
to determine the effect of alginate (found in brown
seaweed) on adhesion formation in a rabbit model
undergoing subtotal flexor tendon laceration. The results
of this study showed significantly greater toe flexion and
less scar tissue formation in the alginate treatment group
compared to the control group. Zhao et al. [59
], using a
canine model, showed that grafted flexor tendons treated
with carbodiimide-derivatized hyaluronic acid had
significantly lower work of flexion compared to controls.
In a canine model, Tanaka et al. [60] showed that the
optimal concentration of 1-ethyl 1-3-(3-dimethylaminopropyl) carbodiimide hydrochloride (EDC)/N-hydroxysuccinimide (NHS) to activate hyaluronic acid and
minimize tendon gliding resistance was 1%. Bates et al.
[61
] also studied the effect of natural molecules mannose
6-phosphate and decorin on range of motion and strength
after flexor tendon repair in the rabbit model. Although
the ultimate strength of the tendon repairs among all
groups was not significantly different, the postoperative
range of motion was significantly higher in the tendon
group that was treated with low-dose mannose 6-phosphate. Sun et al. [62
] reported that in the canine model,
lubricin (boundary lubricant) was present both on the
tendon surface in regions of the tendon exposed to
significant shear and compressive forces.

Gene therapy
Gene therapy aims to treat disorders by the introduction
of engineered genes that code for proteins that are absent
or not normally produced by the host. There are several
vectors that can be used in the delivery of growth factor
genes. Such vectors include adenoviral vectors, adenoassociated viral vectors, and liposome-plasmid vectors.
Zhu et al. [63
] compared the histological tissue reactions
in a rabbit model to adenoviral, adeno-associated viral,
and liposome-plasmid vectors with the early healing
responses of injured flexor tendons. Of the three viral
vectors tested, it appears that the adeno-associated viral
vector is the best vector for gene delivery because it
elicits a minimal adverse response in tendon and it causes
no human diseases [63
,6466].
Much can be learned about the roles of various cytokines
and proteins by analyzing gene expression in injured and
healing tendons. Berglund et al. [67
] analyzed the RNA
expression of rabbit flexor tendons and flexor tendon
sheaths in various stages of healing. The results of this
study showed that while both flexor tendon and sheath
had increased expression of collagen type III mRNA,

type I collagen expression was limited to the sheath.

Increased expression of mRNA for bFGF and transforming growth factor b was limited to the flexor tendon. The
value of this information is that with a better understanding of the healing process, interventions can be
made to modulate specific mRNA expression at critical
time points to increase the strength of healing tendons or
diminish adhesions to surrounding local tissue.

Pulsed-electromagnetic-field therapy
Strauch et al. [68] have demonstrated in a rat Achilles
tendon model that pulsed-electromagnetic-field therapy
configured to enhance Ca2 binding in the growth factor
cascades involved in tissue healing increased the tensile
strength up to 69% compared with control animals. If
similar effects occur in humans, increased strength may
allow for safe early motion with decreased rupture
risk.

Conclusion
We continue to search for the Holy Grail of flexor tendon
repair which will restore function to the hand after these
potentially devastating injuries. A strong repair that does
not gap with early motion and allows for smooth gliding is
a prerequisite for a satisfactory outcome. The use of
biological techniques to maximize healing and strength
and minimize adhesion formation may decrease the need
for complex tenolysis procedures and late flexor tendon
reconstruction. The future of treatment is the marriage of
the scalpel and syringe.

Acknowledgements
We thank Rachel Y. Goldstein, BA, Michael R. Hausman, MD, Karl J.
Jepsen, PhD, Philip Nasser, MS, and Carl Terranova, PhD, for their
contributions to the original research.

References and recommended reading

Papers of particular interest, published within the annual period of review, have
been highlighted as:


of special interest


of outstanding interest
Additional references related to this topic can also be found in the Current
World Literature section in this issue (p. 417).
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2.5 weeks earlier than the other group.

6

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7

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31 McLarney E, Hoffman H, Wolfe SW. Biomechanical analysis of the cruciate

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35 Lee SK, Gargano F, Goldstein RY, Hausman MR. A new combination suture
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36 Lister GD, Kleinert HE, Kutz JE, Atasoy E. Primary flexor tendon repair followed
by immediate controlled mobilization. J Hand Surg [Am] 1977; 2:441451.
37 Matloub HS, Dzwierzynski WW, Erickson S, et al. Magnetic resonance
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38 Taras JS, Gray RM, Culp RW. Complications of flexor tendon injuries. Hand
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39 Ferguson RE, Rinker B. The use of a hydrogel sealant on flexor tendon repairs


to prevent adhesion formation. Ann Plast Surg 2006; 56:5458.
This study reports on the use of a hydrogel sealant to prevent adhesion formation in
zone II flexor tendon injuries in a chicken model. Results of this study showed
significantly decreased work of flexion in the hydrogel sealant-treated group.
40 Sungur N, Uysal A, Kocer U, et al. Prevention of tendon adhesions by the
reconstruction of the tendon sheath with solvent dehydrated bovine pericard:
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41 Cao Y, Zhu B, Xie RG, Tang JB. Influence of core suture purchase length


on strength of four-strand tendon repairs. J Hand Surg [Am] 2006; 31:107
112.
This is an interesting article that compared biomechanical properties of three
different repair methods with a core purchase of either 1.0 or 0.4 cm. The results of
the study show that the use of a 0.4 cm core suture purchase results in a
significantly weaker repair for all three methods.
42 Cao Y, Tang JB. Resistance to motion of flexor tendons and digital edema: an


in vivo study in a chicken model. J Hand Surg [Am] 2006; 31:16451651.
This study assessed edema formation after surgery in a chicken model as well as
the work of flexion of the digital tendon at various times after surgery. The results
show that the work of flexion increased for the first 4 days after surgery and then
leveled off for the next 3 days.
43 Luo J, Mass DP, Phillips CS, He TC. The future of flexor tendon surgery. Hand
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44 Caplan AI, Bruder SP. Mesenchymal stem cells: building blocks for molecular
medicine in the 21st century. Trends Mol Med 2001; 7:259264.
45 Huang D, Balian G, Chhabra AB. Tendon tissue engineering and gene


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This is an excellent summary of the concepts of tissue engineering including cell
therapy, scaffolds and growth factors. The principles and goals of gene therapy are
also reviewed.
46 Chong AK, Ang AD, Goh JC, et al. Bone marrow-derived mesenchymal stem


cells influence early tendon-healing in a rabbit achilles tendon model. J Bone
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This study showed that the addition of bone marrow-derived mesenchymal stem
cells to a repaired tendon improved the histological and biomechanical properties
of the repair site at the 3-week time interval, but not at later intervals.
47 Cao Y, Vacanti JP, Ma X, et al. Generation of neo-tendon using synthetic
polymers seeded with tenocytes. Transplant Proc 1994; 26:33903392.

27 Barrie KA, Tomak SL, Cholewicki J, et al. Effect of suture locking and suture
caliber on fatigue strength of flexor tendon repairs. J Hand Surg [Am] 2001;
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48 Cao Y, Liu Y, Liu W, et al. Bridging tendon defects using autologous tenocyte
engineered tendon in a hen model. Plast Reconstr Surg 2002; 110:1280
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28 Barrie KA, Tomak SL, Cholewicki J, Wolfe SW. The role of multiple strands
and locking sutures on gap formation of flexor tendon repairs during cyclical
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49 Goh JC, Ouyang HW, Teoh SH, et al. Tissue-engineering approach to

the repair and regeneration of tendons and ligaments. Tissue Eng 2003;
9 (Suppl 1):S31S44.

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346 Hand and wrist

50 Awad HA, Butler DL, Harris MT, et al. In vitro characterization of mesenchymal stem cell-seeded collagen scaffolds for tendon repair: effects of initial
seeding density on contraction kinetics. J Biomed Mater Res 2000; 51:233
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51 Cao D, Liu W, Wei X, et al. In vitro tendon engineering with avian tenocytes


and polyglycolic acids: a preliminary report. Tissue Eng 2006; 12:1369
1377.
This study reports on in-vitro tendon engineering in a hen model. The engineered
tendons in this study that were exposed to a constant strain were thinner and had
increased tensile strength compared to the control group.
52 Liu W, Chen B, Deng D, et al. Repair of tendon defect with dermal fibro

blast engineered tendon in a porcine model. Tissue Eng 2006; 12:775
788.
This study showed that dermal fibroblasts could be used in tendon engineering
and result in engineered tendon with similar histological and biomechanical
properties to engineered tendon derived from tenocytes.
53 Hamada Y, Katoh S, Hibino N, et al. Effects of monofilament nylon coated with


basic fibroblast growth factor on endogenous intrasynovial flexor tendon
healing. J Hand Surg [Am] 2006; 31:530540.
This article showed that the use of a monofilament nylon suture coated with bFGF
in tendon repairs resulted in increased cellular density at the repair site and a higher
ultimate strength than the control group.
54 Costa MA, Wu C, Pham BV, et al. Tissue engineering of flexor tendons:


optimization of tenocyte proliferation using growth factor supplementation.
Tissue Eng 2006; 12:19371943.
Growth factors such as platelet-derived growth factor-BB, insulin-like
growth factor-1, and bFGF can be used to significantly increase tenocyte
proliferation and increase the amount of tissue produced for tendon grafting
purposes.
55 McCombe D, Kubicki M, Witschi C, et al. A collagen prolyl 4-hydroxylase


inhibitor reduces adhesions after tendon injury. Clin Orthop Relat Res 2006;
451:251256.
This study showed the effectiveness of an orally administered collagen-synthesis
inhibitor in diminishing adhesion formation after crush injury in a rat model.
56 Akasaka T, Nishida J, Araki S, et al. Hyaluronic acid diminishes the resistance
to excursion after flexor tendon repair: an in vitro biomechanical study.
J Biomech 2005; 38:503507.

59 Zhao C, Sun YL, Amadio PC, et al. Surface treatment of flexor tendon


autografts with carbodiimide-derivatized hyaluronic acid. An in vivo canine
model. J Bone Joint Surg [Am] 2006; 88:21812191.
This study reported that, in a dog model, tendon grafts treated with carbodiimidederivatized hyaluronic acid had significantly lower work of flexion and significantly
lower gliding resistance than controls treated with saline solution.
60 Tanaka T, Sun YL, Zhao C, et al. Optimization of surface modifications of
extrasynovial tendon to improve its gliding ability in a canine model in vitro.
J Orthop Res 2006; 24:15551561.
61 Bates SJ, Morrow E, Zhang AY, et al. Mannose-6-phosphate, an inhibitor of


transforming growth factor-beta, improves range of motion after flexor tendon
repair. J Bone Joint Surg [Am] 2006; 88:24652472.
This study showed that repaired rabbit tendon lacerations treated with a single low
dose of mannose 6-phosphate had significantly better range of motion than the
other treatment groups (control group, decorin treatment group, and high-dose
mannose 6-phosphate group).
62 Sun Y, Berger EJ, Zhao C, et al. Expression and mapping of lubricin in canine


flexor tendon. J Orthop Res 2006; 24:18611868.
This study investigated the distribution of lubricin (boundary lubricant) in a canine
model and demonstrated its presence on the tendon surface and at sites in the
tendon subject to shear force, compression, and tension.
63 Zhu B, Cao Y, Xin KQ, et al. Tissue reactions of adenoviral, adeno-associated


viral, and liposome-plasmid vectors in tendons and comparison with earlystage healing responses of injured flexor tendons. J Hand Surg [Am] 2006;
31:16521660.
This study evaluated the tissue reactions to three different vectors (adenoviral,
adeno-associated viral, and liposome-plasmid) for gene delivery. The lowest
amount of tissue reaction was seen with the adeno-associated viral vector.
64 Schwarz EM. The adeno-associated virus vector for orthopaedic gene
therapy. Clin Orthop Relat Res 2000; 379 (Suppl):S31S39.
65 Erles K, Sebokova P, Schlehofer JR. Update on the prevalence of serum
antibodies (IgG and IgM) to adeno-associated virus (AAV). J Med Virol 1999;
59:406411.
66 Daly TM. Overview of adeno-associated viral vectors. Methods Mol Biol 2004;
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57 Akasaka T, Nishida J, Imaeda T, et al. Effect of hyaluronic acid on the excursion

resistance of tendon graft: a biomechanical in vitro study in a modified human
model. Clin Biomech 2006; 21:810815.
This study demonstrated that the administration of hyaluronic acid diminishes
resistance to motion after human cadaveric extrasynovial tendon graft.

67 Berglund M, Reno C, Hart DA, Wiig M. Patterns of mRNA expression for

matrix molecules and growth factors in flexor tendon injury: differences in the
regulation between tendon and tendon sheath. J Hand Surg [Am] 2006;
31:12791287.
This study analyzed the pattern of expression of mRNA in the tendon and tendon
sheath after flexor tendon injury and showed that the tendon and tendon sheath
had different patterns of mRNA expression.

58 Namba J, Shimada K, Saito M, et al. Modulation of peritendinous adhesion

formation by alginate solution in a rabbit flexor tendon model. J Biomed Mater
Res B Appl Biomater 2007; 80:273279.

68 Strauch B, Patel MK, Rosen DJ, et al. Pulsed magnetic field therapy increases
tensile strength in a rat Achilles tendon repair model. J Hand Surg [Am] 2006;
31:11311135.

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