1. [ RESEARCH REPORT ]
M. TERRY LOGHMANI, PT, MS¹ PT, PhD²
Instrument-Assisted Cross-Fiber Massage
Accelerates Knee Ligament Healing
igament injuries account for up to 50% of sporting injuries,6 with any residual neuromuscular de-
L with the majority being to capsular and extracapsular ligaments
(such as the knee and ankle collateral ligaments).11 Injuries to
these ligaments have traditionally been thought to heal in a
straightforward manner; however, preclinical studies have shown that
ligament healing occurs by the formation of a reparative scar, rather than
ficiency, may explain why a history of
ligament injury is a strong risk factor for
subsequent injury.14,23 Some patients (up
to a third) also continue to experience
significant symptoms even up to 3 years
following capsular or extracapsular liga-
via regeneration, which leaves a deficiency in mechanical properties at ment injury,25 and injuries to these liga-
the completion of healing.7,29 This persistent tissue weakness, combined ments can contribute to the development
of osteoarthritis.24
Controlled laboratory study. stronger (P .05), 39.7% stiffer (P .01), and could To address the short- and long-term
absorb 57.1% more energy before failure (P .05) consequences of capsular and extracapsu-
To investigate the effects of
instrument-assisted cross-fiber massage (IACFM) than contralateral, injured, nontreated ligaments at lar ligament injuries, there is a need for
on tissue-level healing of knee medial collateral 4 weeks postinjury. On histological and scanning simple interventions that facilitate early
ligament (MCL) injuries. electron microscopy assessment, IACFM-treated recovery (accelerate healing) and/or result
ligaments appeared to have improved collagen in a better final outcome (augment heal-
Ligament injuries are common
fiber bundle formation and orientation within the
and significant clinical problems for which there ing). By accelerating tissue-level healing,
scar region than nontreated ligaments. There were
are few established interventions. IACFM repre-
minimal differences between IACFM-treated and
the injured tissue may be less susceptible
sents an intervention that may mediate tissue-level to reinjury during early rehabilitation
contralateral, nontreated ligaments at 12 weeks
healing following ligament injury. and the individual may be able to return
postinjury, although IACFM-treated ligaments were
Bilateral knee MCL injuries were 15.4% stiffer (P .05). to function quicker. By augmenting tissue-
created in 51 rodents, while 7 rodents were level healing, the final product of the heal-
IACFM-accelerated ligament
maintained as ligament-intact, control animals.
healing, possibly via favorable effects on collagen ing process may be enhanced such that the
IACFM was commenced 1 week following injury
and introduced 3 sessions per week for 1 minute formation and organization, but had minimal effect healed tissue more closely approximates
per session. IACFM was introduced unilaterally on the final outcome of healing. These findings are that of the native tissue.
(IACFM-treated), with the contralateral, injured clinically interesting, as there are few established Cross-fiber massage (CFM) may be a
MCL serving as an internal control (nontreated). interventions for ligament injuries, and IACFM
method for accelerating and/or augment-
Thirty-one injured animals received 9 IACFM is a simple and practical therapy technique. J
ing capsular and extracapsular ligament
treatments, while the remaining 20 injured animals Orthop Sports Phys Ther 2009;39(7):506-514.
doi:10.2519/jospt.2009.2997 healing. CFM refers to the application of
received 30 treatments. Ligament biomechani-
cal properties and morphology were assessed at specifically directed forces transverse to
biomechanics, complementary
either 4 or 12 weeks postinjury. the direction of the underlying collagen
therapies, medial collateral ligament, physical
IACFM-treated ligaments were 43.1% therapy, sports medicine substructure in order to induce physi-
ological and/or structural tissue changes.
1
Associate Clinical Professor, Department of Physical Therapy, School of Health and Rehabilitation Sciences, Indiana University, Indianapolis, IN. 2 Assistant Professor and Director
of Research, Department of Physical Therapy, School of Health and Rehabilitation Sciences, Indiana University, Indianapolis, IN. This study was supported in part by grants from
the American Massage Therapy Foundation and TherapyCare Resources, Inc (Indianapolis, IN). The results presented herein represent the conclusions and opinions of the authors.
Publication does not necessarily imply endorsement by the grant providers or endorsement of their products by the authors. No commercial party having a direct interest in the
results of the research supporting this article has or will confer a benefit on the authors or any organization with which the authors are associated. The study protocol for animal use
was approved a priori by the Institutional Animal Care and Use Committee at Indiana University. Address correspondence to M. Terry Loghmani, Department of Physical Therapy,
School of Health and Rehabilitation Sciences, Indiana University, 1140 W Michigan St CF 326, Indianapolis, IN 46202. E-mail: mloghman@iupui.edu.
506 | july 2009 | volume 39 | number 7 | journal of orthopaedic & sports physical therapy

2. It differs from other massage techniques tation. Animals had ad libitum access to
in that there is little motion between the standard rat chow and water at all times,
therapist’s contact and the patient’s skin. and were housed 2 per standard size cage
Instead, CFM involves moving the skin (length, 40 cm; width, 20 cm; height, 20
and subcutaneous tissues over deeper con- cm). All procedures were approved a pri-
nective tissues to exert controlled mechan- ori by The Institutional Animal Care and
ical forces on the latter. As the reparative Use Committee of Indiana University.
cells (fibroblasts) responsible for produc-
ing collagen and forming a scar following Ligament Injury
ligament injury are mechanosensitive,4,26 Fifty-one animals underwent surgery on
it is theorized that CFM facilitates matrix entry to the study to create bilateral knee
production and the restoration of tissue- MCL injuries of their hindlimbs (injured
level mechanical properties. animals). The remaining 7 animals
An addition to the practice of CFM served as age-matched, ligament-intact
has been the use of rigid instruments, cage controls and were not operated on
with the resultant technique referred to (control animals). Following a preopera-
as instrument-assisted CFM (IACFM). tive subcutaneous dose (0.05 mg/kg) of
IACFM appears to be effective in promot- buprenorphine hydrochloride analgesia
ing tissue remodeling, with Davidson et al5 (Buprenex; Reckitt & Colman Pharma-
and Gehlsen et al8 having found increased ceuticals Ltd, Richmond, VA), surgical
fibroblast recruitment and activation in an anesthesia was achieved using a mixture
animal model of Achilles tendon injury. of ketamine (60-80 mg/kg) (Ketaset;
Results of clinical pilot studies also suggest Fort Dodge Animal Health, Fort Dodge,
that IACFM reduces symptoms in individ- IA) and xylazine (7.5 mg/kg) (Sedazine;
uals with carpal tunnel syndrome, patellar Fort Dodge Animal Health), introduced
tendinopathy, and chronic ankle pain.1,17,30 intraperitoneally. Using a sterile tech-
Based on the hypothesized mechanical nique, a 5-mm longitudinal incision was
Instrument-assisted cross-fiber massage
mode of action of IACFM and preliminary made over 1 knee’s medial joint line, and
(IACFM) intervention. (A) The rigid Graston Technique
evidence demonstrating its potential effi- the MCL sharply transected at the joint GT6 tool fabricated from stainless steel has a tapered
cacy, the aim of this study was to examine line using a size-11 scalpel blade. This re- tip,* which permits treatment of small structures.
the short- and long-term effects of IACFM sulted in complete disruption of the MCL IACFM of a (B) human finger, and (C) similar-size
on tissue-level healing of knee medial at its midsubstance and transverse to the rodent knee joint medial collateral ligament using the
GT6 tool. Arrows indicate the direction of movement/
collateral ligament (MCL) injuries in an underlying collagen fiber alignment. No
force application perpendicular to the collagen
established animal model. The primary ligament material was removed, and the substructure of the ligament.
variable of interest was ligament mechani- ligament ends were juxtaposed but not
cal properties, as the ultimate outcome of sutured prior to closing of the skin inci- force through its tip to small structures,
any healing process in a load-bearing tis- sion with a single subcuticular absorb- such as finger collateral ligaments in hu-
sue (such as a ligament) is the restoration able suture. The procedure was repeated mans (in the present study, rat knee-size
of mechanical properties. The secondary on the contralateral knee to create bilat- ligaments) ( ). IACFM was initiated
variable of interest was ligament morphol- eral injuries. All animals demonstrated 1 week postoperatively (postinjury) to al-
ogy, as this may explain differences in tis- normal, symmetrical hindlimb use upon low the initial inflammatory response/
sue mechanical properties. recovery from surgery and were allowed phase of ligament healing to subside. This
normal cage activity (without access to initial delay in the introduction of IACFM
exercise wheels) for the duration of the is consistent with its suggested clinical
study. use following an acute injury. IACFM was
Animals administered with the animals under iso-
Intervention flurane anesthesia (3% at 1.5 L/min for
F
ifty-eight 6-month-old, virgin,
female Sprague-Dawley rats (body IACFM was performed using a rigid tool initial knockdown in a plastic container,
mass, 280-300 g) were purchased fabricated from stainless steel (GT6; Gras- and 1.5% at 1.5 L/min via a face mask for
from Harlan Sprague-Dawley, Inc (In- ton Technique, TherapyCare Resources, maintenance of anesthesia). Approximate-
dianapolis, IN) and acclimated for a Indianapolis, IN). The GT6 instrument ly 250 to 300 g of instrument downward
minimum of 7 days prior to experimen- was used because it is designed to apply force was applied during treatment. This
journal of orthopaedic & sports physical therapy | volume 39 | number 7 | july 2009 | 507

3. [ RESEARCH REPORT ]
force is equivalent to that previously used A
to demonstrate benefits of IACFM on in- Ligament mechanical properties were Femur
jured rat Achilles tendons,8 and was deter- assessed as previously described.27,28
mined by using the massage instrument Hindlimbs destined for mechanical test- Medial
70° collateral
on a force plate, with kinesthetically simi- ing were initially stored at –80°C, with ligament
lar pressure to that which would be used the knee tissues intact. Postmortem stor-
clinically to treat a ligament of comparable age of ligaments by freezing does not Wood’s low Tibia
size at an equivalent tissue depth (eg, col- influence their mechanical properties.33 melting-point
metal
lateral ligament of a human interphalan- On the day of mechanical testing, the
geal joint). Thirty-one injured animals hindlimbs were allowed to thaw to room
were treated 3 times per week for 3 weeks temperature in phosphate-buffered sa- B
(total treatments, 9), while the other 20 line (PBS). Femoral-MCL-tibia (FMT) ess
35 ffn
injured animals were treated 3 times per complexes were prepared by dissect- Ultimate force Sti
30
week for 10 weeks (total treatments, 30). ing clear extraneous tissue (including
Force (N)
25
The number of treatments in the latter the joint capsule and adherent medial 20
animals is more than would typically be meniscus), while keeping the MCL and 15
10 Energy to failure
introduced in a clinical setting; however, its insertion sites hydrated with PBS.
5
these were implemented to maximize the The femoral and tibial insertions of the
0
potential of finding any long-term benefit MCL were left intact, and the proximal 0 0.2 0.4 0.6 0.8 1 1.2 1.4 1.6 1.8
of IACFM. IACFM was applied to the left tibia growth plate was removed to permit Displacement (mm)
MCL in injured animals for 1 minute per more space within the knee joint during
session (IACFM-treated). This treatment testing. MCL thickness and width were Tensile mechanical testing of rat knee
duration was based on the recommended measured optically at the knee joint line, medial collateral ligament (MCL). (A) Representative
image of the setup for testing. Femur-MCL-tibia
clinical use of IACFM for the treatment of and MCL area estimated using an ellipti-
complexes were placed in fixtures that supported
isolated tissue lesions3 and evidence from cal geometry.20 Each FMT complex was ("cupped") the distal femur and proximal tibia to
previous preclinical studies demonstrat- placed in a customized testing jig, with prevent bone slippage, and fixed in place using
ing the efficacy of short-duration IACFM the knee joint positioned in 70° flexion, Wood's low-melting-point metal. The knee joint
interventions.5,8 The contralateral injured for MCL testing. This position appears to was positioned in 70° of flexion for testing. (B)
Representative force displacement curve for a rat
MCL in these animals served as an inter- load all ligament fibers simultaneously.20
knee MCL tensile mechanical test. Derived properties
nal control and did not receive IACFM The femoral and tibial portions were include ultimate force (peak on the curve on the
(nontreated). The 7 control animals were embedded in Wood’s low-melting-point y-axis), stiffness (slope of the linear portion of the
not treated with IACFM. metal (bismuth alloy LMA-117; Small curve), and energy absorbed prior to failure (area
Parts, Inc, Miami Lakes, FL) for fixation. under the curve).
The jig was coupled to an electromag-
netic material testing device (TestBench displacement data were collected at 100
Animals were euthanized postinjury at 200 N ELF LM-1; EnduraTEC Systems Hz, and the mechanical properties of ul-
either 4 weeks (all animals treated for 9 Group, Bose Corp, Minnetonka, MN), timate force (N), stiffness (N/mm), and
sessions [n = 31] and 2 control animals) equipped with a 50-N load cell ( energy to failure (mJ) obtained from the
or 12 weeks (all animals treated for 30 2A). This system possesses a force and force-displacement curves ( ).
sessions [n = 20] and 5 control animals). displacement resolution of 0.01 N and
Animals euthanized at 4 weeks had both 0.001 mm, respectively. A preload of 0.05
hindlimbs harvested and prepared for N was applied and the ligaments were Immediately after harvest, specimens for
mechanical testing (injured animals, n preconditioned by cyclically loading at 1 scanning electron microscopy were placed
= 18), scanning electron microscopy (in- Hz for 10 cycles to 1% strain to reduce in a custom limb frame that held the knee
jured, n = 11; control animals, n = 2), or the effect of deep freezing on low-load positioned in 70° flexion. The MCL was
histological assessment (injured animals, mechanical properties.33 The ligaments exposed and drip fixed for 1 hour with
n = 2). Animals euthanized at 12 weeks were unloaded and allowed to recover for 2.5% glutaraldehyde in 0.1 mol sodium
had both hindlimbs removed and pre- 1.5 minutes, while being kept moist with cacodylate buffer (pH 7.4) (Electron Mi-
pared for mechanical testing (injured, n = PBS. Following tissue recovery, ligaments croscopy Services, Hatfield, PA). After
17; control animals, n = 4) or histological were again preloaded (0.05 N) and pulled drip fixation, the MCLs were removed
assessment (injured, n = 3; control ani- to tensile failure in displacement control using a microsurgical scalpel, with the
mals, n = 1). at a rate of 0.8 mm/s (~10%/s). Force and femoral insertion marked by an angled
508 | july 2009 | volume 39 | number 7 | journal of orthopaedic & sports physical therapy

4. cut. Any adherent tissue was removed
under a dissecting microscope. Liga-
ments were then rinsed twice in buffered
solution and dehydrated by immersing
for 15 minutes each in fresh solutions of
70%, 95%, and 100% ethyl alcohol. They
were subsequently immersed in liquid ni-
trogen, placed on precooled microscope
slides, and fractured under a dissecting
microscope in the sagittal plane from the
femoral to tibial end using one half of a
precooled, double-edged stainless steel
razor blade (Electron Microscopy Scienc-
es, Hatfield, PA). The ligament samples
were then critical point dried (Samdri
model 780A; Tousimis Research Corp,
Rockville, MA), mounted on 10-mm
scanning electron microscopy specimen
mount blocks using nonconductive adhe-
sive tabs (Ted Pella, Inc, Redding, CA),
and surrounded by colloidal silver paste
(Electron Microscopy Sciences, Hatfield,
PA). After drying overnight in a vacuum
dessicator with dissecant, the samples
were sputter coated with gold-palladium Representative images of surgically transected, untreated rat knee medial collateral ligaments (MCL)
(Polaron, Energy Beam Sciences, East at (A) 4 and (B) 12 weeks following injury. Arrow indicates location of scar (initial injury). Abbreviations: F, femoral
Gramby, CT) for 1.75 minutes, and stored origin of the MCL; T, tibial insertion of the MCL.
in a vacuum dessicator with desiccant un-
til imaged. The samples were imaged on plane thin (4 μm) sections were cut us- contralateral nontreated MCLs. Paired t
a scanning electron microscope (JSM- ing a rotary microtome (Reichert-Jung test results were subsequently confirmed
6390LV; JEOL Ltd, Peabody, MA), using Model 2050; Reichert-Jung, Heidelberg, by calculating mean percent differences
a 5-kV accelerating voltage and working Germany), mounted onto microscope between IACFM-treated and nontreated
distance of 11 mm. The ligaments were slides, and stained with Harris hematoxy- MCLs [(IACFM-treated – IACFM-non-
aligned at low magnification (approxi- lin and eosin on a linear stainer (Shandon treated) ÷ nontreated 100%], which
mately 25) by orienting the femoral end Linistain GLX; Thermo Electron Corp, were analyzed using single sample t tests
of the ligament to the top of the screen, Waltham, MA). Three sections per speci- with a population mean of 0%.
and the residual and scar regions were men were qualitatively assessed under
identified. The morphology of collagen light microscopy using a Nikon Optio-
fibrils and fibers for each ligament in phot 2 microscope (Nikon, Inc, Garden
the residual and scar tissue regions were City, NY).
examined at magnifications of 250 to
T
here were no operative or post-
11000, and digitally imaged. operative complications. Animals
Statistical analyses were performed using assessed at 12 weeks postinjury were
Histology SPSS, Version 16.0 (SPSS Inc, Chicago, significantly heavier than those assessed
Ligaments for histology were fixed under IL). All comparisons were 2-tailed, with at 4 weeks (mean SD, 291.4 13.2 g
tension in 4% paraformaldehyde at 4°C a level of significance set at 0.05. Un- versus 313.5 22.6 g; P .05). There
for 48 hours. They were subsequently paired t tests were performed to assess were no differences in weight between
dehydrated in graded alcohols, washed time (4 versus 12 weeks postinjury) and injured and control animals (P = .76).
with 2 changes of xylene, and infiltrated group (injured versus control animals) ef-
and embedded in paraffin, using a Shan- fects on body mass. IACFM effects were
don automatic tissue processor (Thermo principally determined using paired t All surgically induced ligament defects
Electron Corp, Waltham, MA). Sagittal tests to compare IACFM-treated and were bridged with scar tissue at the time
journal of orthopaedic & sports physical therapy | volume 39 | number 7 | july 2009 | 509

5. [ RESEARCH REPORT ]
ligaments did not differ significantly at
A B C
either 4 (5.46 1.01 mm2 versus 5.16
50 30 50 2
Noninjured ligament stiffness 1.55 mm ; P = .45) or 12 (3.80 1.02
Noninjured ligament strength
25 Noninjured ligament energy mm2 versus 4.09 0.79 mm2; P = .29)
40 † 40
weeks postinjury.
*
Energy to failure (mJ)
20 *
Ultimate force (N)
30 Stiffness (N/mm) 30
15
Ligament Mechanical Properties
20 20
At 4 weeks postinjury, IACFM-treated
10 ligaments could resist 6.4 N (95% con-
10 10
fidence interval [CI], 1.6 to 11.2 N; P =
5
.01) greater force than contralateral non-
0 0 0 treated ligaments (FIGURE 4A). This was
reflected by IACFM-treated ligaments
Nontreated IACFM-treated having 43.1% (95% CI, 8.2% to 78.0%;
P = .02) greater mean difference in ten-
FIGURE 4. Effect of 9 sessions (1 minute per session) of instrument-assisted cross-fiber massage (IACFM) on sile strength than nontreated ligaments.
knee medial collateral ligament (MCL) mechanical properties assessed at 4 weeks following injury. IACFM-treated
Similarly, IACFM-treated ligaments had
ligaments had greater (A) ultimate force, (B) stiffness, and (C) energy to ultimate force than contralateral,
nontreated ligaments. *Indicates P .05. †Indicates P .01, as determined with paired t test. The dashed line
4.9 N/mm (95% CI, 2.4 to 7.4 N/mm; P
indicates mean mechanical properties within uninjured MCLs from age-matched, cage control animals. Error bars = .001) (FIGURE 4B) and 5.8 mJ (95% CI,
indicate SD. 0.7 to 10.9 mJ; P .05) (FIGURE 4C) greater
stiffness and energy to failure at 4 weeks
postinjury than nontreated ligaments, re-
A B C spectively. This was reflected by IACFM-
50 30
Noninjured ligament stiffness
50 treated ligaments being 39.7% (95% CI,
Noninjured ligament strength
* Noninjured ligament energy
15.9% to 63.5%; P .01) stiffer and being
25
40 40 able to absorb 57.1% (95% CI, 3.4% to
110.9%; P = .04) greater energy before
Energy to Failure (mJ)
20
Ultimate Force (N)
Stiffness (N/mm)
30 30
failure than nontreated ligaments.
15
At 12 weeks postinjury, IACFM-treat-
20 20
10
ed ligaments had 2.6 N/mm (95% CI, 0.2
to 5.0 N/mm; P .05) greater stiffness
10 10
5 than nontreated ligaments, resulting in
the former being 15.4% (95% CI, 0.1%-
0 0 0
30.7%; P .05) stiffer (FIGURE 5B). Howev-
Nontreated IACFM-treated er, there were no differences at 12 weeks
postinjury between IACFM-treated and
FIGURE 5. Effect of 30 sessions (1 minute per session) of instrument-assisted cross-fiber massage (IACFM) on nontreated ligaments in ultimate force
knee medial collateral ligament (MCL) mechanical properties assessed at 12 weeks following injury. IACFM-treated (1.1 N; 95% CI, –2.6 to 4.7 N; P = .54)
ligaments had (A) equivalent ultimate force, (B) enhanced stiffness, and (C) equivalent energy to failure than (FIGURE 5A) or energy to failure (–0.6 mJ;
contralateral, nontreated ligaments. *Indicates P .05, as determined with paired t test. The dashed line indicates 95% CI, –6.7 to 5.5 mJ; P = .84) (FIGURE
mean mechanical properties within uninjured MCLs from age-matched, cage-control animals. Error bars indicate SD.
5C). Mechanical properties of ligaments
in injured animals at both 4 and 12 weeks
of harvest. At 4 weeks postinjury, the the uninjured portions of the ligament postinjury remained inferior to intact,
injured region was clearly distinguishable (FIGURE 3B). There were no grossly noninjured ligaments from control ani-
from the uninjured ligament tissue by observable differences between IACFM- mals (P .05).
the presence of a thickened, somewhat treated and nontreated ligaments at either
translucent, pinkish scar (FIGURE 3A). In 4 or 12 weeks postinjury; however, non-
; Ligament Microscopic Morphology
comparison, ligaments at 12 weeks postin- treated ligaments often had more adhe- Light microscopy of noninjured liga-
jury had difficult-to-see whitish scars that sions and granular tissue, and were more ments from control animals revealed a
were relatively indistinguishable from the difficult to harvest than IACFM-treated uniform appearance of tightly packed,
uninjured tissue, and the thickness of the ligaments. Mean SD cross-sectional well-aligned collagen fibrils with inter-
scar region was continuous with that of area of IACFM-treated and nontreated spersed fibroblasts aligned parallel to
510 | july 2009 | volume 39 | number 7 | journal of orthopaedic & sports physical therapy

6. the fibrils ( ). In contrast, liga-
ments from injured animals appeared to
have scar morphology with extracellular
matrix disorganization and hypercellu-
larity, particularly at 4 weeks postinjury
( ). The scar region of IACFM-
treated ligaments at 4 weeks postinjury
also appeared to have greater cellularity,
with collagen fiber bundles appearing to
be orientated more along the longitudi-
nal axis of the ligament than observed in
contralateral nontreated ligaments (FIG
). At 12 weeks postinjury, there
were limited histological differences be-
Representative histological sections from (A) noninjured knee medial collateral ligament (MCL) in
a cage-control animal, (B) scar region in a nontreated MCL at 4 weeks following injury, (C) scar region in an tween IACFM-treated and nontreated
instrument-assisted cross-fiber massage (IACFM)-treated MCL at 4 weeks following injury, (D) scar region in a ligaments ( ).
nontreated MCL at 12 weeks following injury, and (E) scar region in an IACFM-treated MCL at 12 weeks following Ligaments from injured, but not con-
injury. Black arrows indicate fibroblasts aligned parallel to the collagen fibrils in a noninjured ligament. White trol, animals had granular tissue at low
arrows indicate scar region in injured ligaments.
magnification ( 25) on scanning elec-
tron microscopy and IACFM-treated
ligaments appeared to have less sur-
rounding granular tissue compared to
nontreated ligaments, supporting the
macroscopic observations ( ). At
higher scanning electron microscopy
magnifications ( 250- 6500), the scar
region of IACFM-treated ligaments ap-
peared to have improved collagen fiber
bundle formation and orientation within
the scar region compared to nontreated
ligaments, supporting the light micros-
copy observations ( ).
T
his study investigated the po-
tential utility of manual therapy in
the form of IACFM on ligament
healing. Results indicate that IACFM-
treated ligaments were 43% stronger,
40% stiffer, and able to absorb 57% more
energy than contralateral, nontreated, in-
jured ligaments at 4 weeks following in-
jury. These mechanical differences may
have resulted from favorable effects of
IACFM on the organization of the under-
lying collagen substructure, as suggested
Representative scanning electron microscopy images taken from an (A) intact knee medial collateral
ligament (MCL) in a control animal, (B) nontreated MCL at 4 weeks following injury, and (C) instrument-
by preliminary light microscopy and
assisted cross-fiber massage (IACFM)-treated MCL at 4 weeks following injury. Images were taken at low ( 25) scanning electron microscopy analyses.
magnification. Note the close appearance of the IACFM-treated ligament (C) to the noninjured ligament from a The latter needs to be confirmed by way
control animal (A). Also, note the large amount of surrounding granulation tissue in the nontreated, but injured of more in-depth quantitative analyses
ligament (C) relative to the other 2 ligaments.
in future studies. In contrast, there was
journal of orthopaedic & sports physical therapy | volume 39 | number 7 | july 2009 | 511

7. [ RESEARCH REPORT ]
How IACFM facilitates the restoration
of ligament tensile mechanical properties
following injury was not investigated in
detail in the current study, as the primary
purpose was to provide proof-of-concept
evidence for the utility of IACFM. How-
ever, preliminary light microscope and
scanning electron microscopy assess-
ments suggest that IACFM may enhance
restoration of ligament biomechanical
healing by optimizing the organization
of the collagen substructure. Collagen (in
particular, type 1 collagen) is the primary
load-bearing molecule in ligament that
endows tensile strength, and is ordered
hierarchically into fibrils and fibers.21
The alignment and organization of newly
formed collagen fibers in the direction of
tensile loads during healing influences
ligament mechanical properties.19,20 The
qualitatively improved collagen fiber or-
Representative scanning electron microscopy images taken from the scar region of a nontreated (A,
ganization observed within the scar re-
B), and instrument-assisted cross-fiber massage (IACFM) treated ligament (C, D) at 4 weeks following injury.
Images were taken at medium ( 250) (A, C), and high ( 6500) (B, D) magnification. Note the improved collagen gion of IACFM-treated ligaments in the
fiber bundle formation and orientation within the scar region of the IACFM-treated ligament (C, D) relative to the current study is a possible explanation
nontreated ligament (A, B). for why IACFM-treated ligaments had
enhanced tensile mechanical properties.
minimal to no effect of IACFM on liga- servative treatment and surgical repair This will be the focus of future quantita-
ment healing when assessed at 12 weeks producing similar outcomes irrespec- tive studies into IACFM effects on liga-
following injury, with the only difference tive of the extent of the initial ligament ment morphology.
between IACFM-treated and nontreated damage. 9,13,22 Consequently, there is a In addition to more detailed studies
ligaments being 15% greater stiffness in need to establish interventions other into IACFM effects on ligament mor-
the former. Overall, the findings of this than surgery for influencing ligament phology, studies are planned to explore
study suggest that IACFM accelerates healing. Numerous preclinical studies potential molecular mechanisms by
early tissue-level healing following liga- have investigated the utility of novel which IACFM generates its biomechani-
ment injury, but does little in terms of interventions targeting ligament heal- cal effects. Our working hypothesis is that
augmenting healing. ing, including the use of gene therapies, IACFM has an underlying effect on colla-
The findings of the current study are growth factors, biological scaffolds, stem gen, which may include effects on its syn-
interesting in that a relatively simple and cell therapies, and biophysical modali- thesis, maturation, and/or cross-linking.
practical manual therapy technique was ties.10,15,18,32 While each of these direc- To have such effects, IACFM must influ-
found to enhance early recovery of liga- tions has shown promise in influencing ence the fibroblastic cells responsible for
ment biomechanical properties follow- ligament healing, the techniques are producing collagen. This potential effect
ing acute injury. This may be clinically far from being translated into the clini- is supported by previous work that found
relevant, as there are currently limited cal realm and their eventual costs may that IACFM increases fibroblast recruit-
established treatment options for me- prohibit wide use in mainstream clinical ment and activation in a rodent Achilles
diating tissue-level ligament healing. practice. In contrast, IACFM may have tendon injury model.5,8 It is plausible
It is clear from preclinical and clinical clinical utility, as it is currently readily that IACFM presents a direct mechani-
studies that surgery with or without im- available and practical from the sense cal stimulus to the extracellular matrix,
mobilization is not indicated for most that gains in ligament biomechanical which is subsequently transduced into a
capsular and extracapsular ligament properties were produced in the current cellular response. A candidate mechan-
injuries. This holds true for both par- study using a relatively limited number otransduction pathway for this response
tial- and full-thickness ligament tears, of short treatment sessions (9 total ses- deserving of future investigation is the ex-
with comparative studies showing con- sions of 1-minute duration each). tracellular matrix-integrin-cytoskeleton
512 | july 2009 | volume 39 | number 7 | journal of orthopaedic & sports physical therapy

8. axis. Integrins are a family of glycoprotein of the ligament-healing process and is an enabling quicker return to function with
molecules that connect extracellularly important preclinical outcome; however, less susceptibility to reinjury.
with the extracellular matrix and intrac- it is plausible that IACFM accelerates Careful interpretation of this
ellularly with the cytoskeleton and other ligament biomechanical healing without controlled animal study is warranted
cytoplasmic constituents.12 This creates a influencing symptom recovery. Also, the until its findings are confirmed by clini-
transmembrane axis that mechanically establishment of IACFM benefits via the cal studies.
links the extracellular matrix with the ex vivo testing of MCL tensile proper-
cytoplasmic constituents of the cell to ties with the knee at 70° flexion may not ACKNOWLEDGEMENTS: The authors would
transmit external stimuli (such as those represent the most clinically translatable like to acknowledge the following student re-
associated with IACFM) directly to the outcome. While testing at 70° knee flex- search assistants from the Doctor of Physical
internal environment of the cell to alter ion is reported to load all fibers of the rat Therapy Program at Indiana University who
gene expression and protein synthesis. MCL simultaneously,20 it is plausible that contributed to this study: Keith Avin, Monica
The current study provides supportive alternative joint positions provide bet- Beaman, Marie DeWolf, Monica Eberle, Ja-
evidence for the potential clinical use of ter tests of functionally important por- mie Grogg, Allison Herriot, Kristen Kastner,
IACFM in the treatment of capsular and tions of the ligament. Similarly, as the John Kiesel, Jessica Lassiter, Kristen Meade,
extracapsular ligament injuries; however, MCL was isolated for mechanical test- Kory Risner, Heidi Streeter, Lynn Taylor, and
the findings need to be carefully inter- ing, the contribution of other structures Mark Watson. We also appreciate the support
preted in light of acknowledged limita- that contribute to the in vivo resistance received from the Histology Laboratory and
tions. First, the study was performed in of knee valgus forces were not assessed. Electron Microscopy Center, Department of
an animal model, wherein the knee MCL It is possible that other passive and ac- Anatomy and Cell Biology, Indiana Univer-
was injured via surgical transection. This tive restraints are able to compensate for sity School of Medicine.
is a highly reproducible and established injury to the MCL in the clinical setting,
model for the preclinical testing of in- reducing the potential clinical effect size
terventions for ligament injuries16,20,29,31; of IACFM during ligament healing.
however, the ability of the model to pre-
1. Burke J, Buchberger DJ, Carey-Loghmani MT,
dict the clinical scenario wherein liga- Dougherty PE, Greco DS, Dishman JD. A pilot
ments are injured via excessive tensile study comparing two manual therapy interven-
load has not been established. Second, the tions for carpal tunnel syndrome. J Manipulative
I
n summary, this study suggests
Physiol Ther. 2007;30:50-61. http://dx.doi.
size of rodent tissues in relation to those that IACFM may accelerate early
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of humans raises scaling issues in terms tissue-level healing following acute 2. Burroughs P, Dahners LE. The effect of enforced
of intervention application and response. capsular/extracapsular ligament injury exercise on the healing of ligament injuries. Am
We addressed this issue by performing but it has minimal to no effect in terms J Sports Med. 1990;18:376-378.
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IACFM to rodent ligaments with the of augmenting the overall outcome of the
technique of instrumented-assisted soft tissue
same tool and force as those used clinical- ligament-healing process. This finding mobilization. In: Hyde T, Genenbach M, eds.
ly to treat similar-size ligaments (finger supports a theoretically sound argument Conservative Management of Sports Injuries.
collateral ligaments). Third, between- for the use of IACFM after acute ligament Sudbury, MA: Jones & Bartlett Publishers;
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as activity has previously been shown ranted until its findings are confirmed by tion in fibroblasts. Appl Physiol Nutr Metab.
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2007;14:641-645. http://dx.doi.org/10.1197/j.
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aem.2007.03.1354
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