REVIEW ARTICLE

Tendon: Biology, Biomechanics, Repair, Growth

Factors, and Evolving Treatment Options
Roshan James, MS, Girish Kesturu, PhD, Gary Balian, PhD, A. Bobby Chhabra, MD
Surgical treatment of tendon ruptures and lacerations is currently the most common therapeutic modality. Tendon
repair in the hand involves a slow repair process, which results in inferior repair tissue and often a failure to obtain
full active range of motion. The initial stages of repair include the formation of functionally weak tissue that is not
capable of supporting tensile forces that allow early active range of motion. Immobilization of the digit or limb will
promote faster healing but inevitably results in the formation of adhesions between the tendon and tendon sheath, which
leads to friction and reduced gliding. Loading during the healing phase is critical to avoid these adhesions but
involves increased risk of rupture of the repaired tendon. Understanding the biology and organization of the native
tendon and the process of morphogenesis of tendon tissue is necessary to improve current treatment modalities.
Screening the genes expressed during tendon morphogenesis and determining the growth factors most crucial for
tendon development will likely lead to treatment options that result in superior repair tissue and ultimately
improved functional outcomes. (J Hand Surg 2008;33A:102112. Copyright 2008 by the American Society for
Surgery of the Hand.)
Key words Collagen, extracellular matrix, gene expression, growth factors, healing, tendinogenesis, repair and
regeneration.

F THE 33 MILLION MUSCULOSKELETAL injuries

reported in the United States per year, roughly
50% involve injuries to the soft tissue including
tendon and ligament.1,2 As larger portions of the general
population participate in physical and recreational activities
every year, the frequency of soft tissue injuries is likely to
increase as well, resulting in increasing health care costs and
patient morbidity. In most cases of tendon laceration or
rupture, surgical intervention is required to direct the natural

From the Department of Orthopaedic Surgery, Orthopaedic

Research Laboratories, University of Virginia Health System;
University of Virginia Hand Center, University of Virginia
Health System; Department of Biochemistry and Molecular
Genetics, University of Virginia Health System; and
Department of Biomedical Engineering, University of Virginia
Health System, Charlottesville, VA.
Received for publication April 16, 2007; accepted in
revised form September 12, 2007.
No benets in any form have been received or will be
received from a commercial party related directly or
indirectly to the subject of this article.
Supported by research grant AR52891 from the
NIAMS, NIH, and by a OREF-Zimmer Career
Development Award to A.B.C.
Corresponding author: A. Bobby Chhabra, MD, 400 Ray C.
Hunt Drive, Suite 330, University of Virginia,
Charlottesville, VA 22908-0159; e-mail:
ac2h@hscmail.mcc.virginia.edu.
0363-5023/08/33A01-0019$34.00/0
doi:10.1016/j.jhsa.2007.09.007

102 ASSH Published by Elsevier, Inc.

process of healing, and occasionally the damage exceeds the

natural ability to repair even with existing treatment
modalities. Tendon repair is a slow process that is
complicated by the need to provide appropriate and timely
tension to the repair tissue. This review covers topics from
tendon biology and functionality, the normal healing
process, and the role of polypeptide factors in the repair
process with speculation on how these factors may improve
tendon repair and surgical outcomes.
Tendon is a unit of musculoskeletal tissue that transmits
force from muscle to bone. Lacerations, ruptures, or
inflammation of the tendon cause marked morbidity and
can have a major impact on work, recreational activities,
and daily needs. Normal tendon consists of soft and fibrous
connective tissue that is composed of densely packed
collagen fiber bundles aligned parallel to the longitudinal
tendon axis and surrounded by a tendon sheath also
consisting of extracellular matrix components. Collagen
constitutes 75% of the dry tendon weight and functions
chiefly to withstand and transmit large forces between
muscle and bone.1 The well-organized tendon architecture
supports large tensile forces and glides readily under tension
to transmit force generated by muscle contraction to the
bone to cause movement.
Tendon is stronger per unit area than muscle, and its
tensile strength equals that of bone, although it is flexible
and slightly extensible. The parallel arrangement of tendon
collagen fibers resists tension so that contractile energy is not
lost during transmission from muscle to the bone. Tendon
strength, however, does not allow for a wide margin of
safety; forces generated by muscle during various power-

TENDON DEVELOPMENT, REPAIR, AND REGENERATION

intensive activities may approach the maximum transmittable

tendon force and lead to rupture, tear, or degeneration.
Tendon repair or replacement begins with the
reestablishment of tendon fiber continuity and the gliding
mechanism. Injury initiates several signaling events that
recruit fibroblasts and stimulate the local tenocyte population
to synthesize collagen and other extracellular components,
establishing physical continuity at the site. With further
appropriate stimuli, such as mechanical stress and strain,
remodeling restores partial or close-to-normal function. The
repair process is slow and characterized by a scar with
mechanically inferior tissue, at least initially. Lack of use or
morbidity leads to extensive scarring and adhesions; these in
turn impede tendon gliding and have a negative impact on
flexor tendon repair in the digit. Excessive stress during
healing can cause tendon rupture. To improve the results of
tendon repair, this complex process will require a healing
response that is enhanced by a combination of treatments,
including growth factors, mechanical stimulation, tissue
engineering, and/or gene therapy. These treatment
modalities may improve tissue healing, tendon gliding,
mechanical strength, and return to normal function while
preventing tendon gapping, ruptures, and extensive
adhesions.
TENDON BIOLOGY
The musculotendinous unit is composed predominately of
collagen fibers and rod- or spindle-shaped fibroblast-like
cells (tenocytes) within a well-ordered extracellular matrix
(ECM)3,4 (Fig. 1). Collagen is synthesized by the tenocytes
and constitutes the basic structural unit of tendon. The
collagen polypeptides form a triple helix, which selfassembles into collagen fibrils with intermolecular cross-links
that form between adjacent helixes.5,6 The parallel
organization of the collagen helixes into fibrils and the
intermolecular cross-linking leads to an increase in tendon
tensile strength. The collagen polypeptides and the ensuing
triple helix are synthesized inside the cell, secreted into the
ECM, and assembled into the microfibrillar units that
constitute the collagen fibers. The major fibrillar component
of tendon is type I collagen predominately, whereas type III
collagen is present in the endotenon and epitenon. During
the process of repair, collagen fiber diameter is notably
smaller, thus reducing the tensile strength of tendon.7,8 Type
III collagen synthesis increases during the early phase of
repair and remodeling and decreases as type I collagen
production increases and becomes highly organized into
fibrillar structures of the ECM (SL Woo, JA Buckwalter,
presented at the AAOS/NIH/ORS workshop, 1987).9,10
Collagen type V is cross-linked to other collagen types and
regulates the characteristics of fibrillar structures in
tendon.11,12
The ECM contains other proteins and proteoglycans
such as decorin and aggrecan. Water represents
approximately 55% of the weight of tendon, is present
mostly in the ECM, and is believed to reduce friction,

103

facilitating the gliding of fibrils in response to mechanical

loading.13 Elastin fibers and several glycoproteins are also
integral parts of tendon ECM and provide functional
stability to the collagen fibers.
Collagen fibrils, 100 500 nm in diameter, are bundled
into large fibers that are evident throughout the tendon,
visible under light microscopy as a crimped or a sinusoidal
pattern that facilitates a 1% to 3% elongation of the
tendon.8,14 16 This elongation of the individual fibers serves
to buffer the tendon from sudden mechanical loading.
Interactions between collagen fibrils at the macromolecular
level leading to the fiber unit architecture dictate the
strength of tendon. Spindle-shaped tendon fibroblasts are
arranged between collagen fibers and synthesize and
maintain the ECM. The collagen fiber structural units are
bound into bundles by the endotenon to give higher
structural units called fascicles, which in turn are bound
together by epitenon to form the tendon.4,13,15 The
endotenon contains the vascular, lymphatic, and neural
transmission routes to maintain tendon fibroblasts, and the
epitenon binds the fascicles together and supplies blood
vessels and tracts for the lymphatics and nerves.17 In the
hand, tendons bend sharply around the joints and are
enclosed by a tendon sheath and a pulley system. This
sheath is covered with synovial cells that lubricate and assist
the enclosed tendons and reduce sliding friction. Tendons
not enclosed within a sheath with synovial fluid move in a
straight line and are surrounded by a continuous paratenon
(eg, Achilles tendon). Paratenon is a loose connective tissue
through which blood vessels enter and vascularize the
endotenon and epitenon.
TENDON FORCE CURVE
Biomechanical properties of tendons during their repair and
regeneration have been studied extensively and their
properties compared with normal tendon. These tests have
shown that current procedures used for repair produce a
tissue with biomechanical properties that are inferior to
those of normal tendon. Attempts at improving the
mechanical properties of repair tissue has led to the design
and testing of new therapies, including tissue-engineering
techniques, followed by biomechanical testing of the
regenerate tissue. Mechanical testing involves separate clamps
to grip the muscle-tendon complex at one end and the
bone at the other end ensuring that the ends are held firmly
without slippage, the tendon is loaded along its longitudinal
axis, and the force and displacement are recorded until the
tissue fails.18 The data from biomechanical tests are
normalized to the initial cross-sectional area and plotted
against the strain or percentage elongation of the tendon.
A typical stress-strain curve has 3 distinctive regions1921
(Fig. 2): (1) A toe region that corresponds with the straightening
of the zigzag pattern or crimp that is visible by polarized light
microscopy of the collagen fiber bundles. This pattern
disappears under tension and then reappears when the stress is

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TENDON DEVELOPMENT, REPAIR, AND REGENERATION

FIGURE 1: Growth factors released by tenocytes in response to local stimuli modulate signaling events that lead to gene expression and protein
synthesis. Collagens and proteoglycans are components of the ECM critical to tendinogenesis. The triple helical collagen molecules form
microbrils that are bundled together to attain macroscopic structures (collagen bers) with a crimped pattern. These bundles give rise to a
higher-order structure (fascicles) that constitute tendons. A loose connective tissue sheath that is rich in blood vessels and has a nerve supply
encloses each ber bundle and tendon.

released. Elastin fibers present in the ECM may be partly

responsible for bringing the stretched collagen bundles back to
the resting state. (2) Immediately after the toe region is the linear
region. The slope of this region is constant and is referred to as

Youngs modulus, or stiffness. At this point, the collagen fiber

bundles are no longer crimped. (3) Beyond the linear region,
collagen fibers fail in an unpredictable fashion; tears occur in the
tendon leading to rupture.

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TENDON DEVELOPMENT, REPAIR, AND REGENERATION

FIGURE 2: Stress-strain curve of normal tendon failed in tension.

(Reprinted with permission from the Annual Review of Biomedical
Engineering, Volume 6, 2004 by Annual Reviews
www.annualreviews.org.)

The mechanical properties of tendon may be correlated

at the molecular level with the mechanical characteristics of
the collagen fibers.22 Tendon viscoelastic behavior,20,23
which is the result of complex interactions between various
components, is dependent on age and activity. Tendons do
not usually fail or rupture under normal conditions;
therefore, it is more appropriate to quantify the physical
properties within the linear region, including stress
relaxation, creep, hysteresis loop, and viscoelasticity. The
rate of elongation that the tendon is subjected to modulates
the amount of load transferred. This necessitates the design
of functional parameters based on in vivo function rather
than on a comparison of parameters such as stiffness and
maximum force. This approach to the problem of tendon
repair may better define the biomechanical characteristics of
the regenerate tissue.
REPAIR AND REGENERATION
The restoration of normal tendon function after injury
requires reestablishment of tendon fibers and the gliding
mechanism between tendon and its surrounding
structures.24 26 The initial stage of repair involves formation
of scar tissue that provides continuity at the injury site27;
however, lack of mechanical stimulus on the tendon will
cause proliferation of scar tissue and subsequent adhesions
that are undesirable and harmful because they impede
normal tendon function, particularly in the hand. Although
stability to the injury site is necessary, mobility is critical, and
mechanical loading that is associated with motion of the
healing tendon decreases the formation of postoperative
adhesions and increases the strength. After tendon injury, the
body initiates a cascade of distinct events or phases
distinguishable by the cellular and biochemical processes that
occur. The sequence of repair involves a progression
through 3 stages: tissue inflammation, cell proliferation, and
remodeling28 36 (Fig. 3).
Inammatory Stage
Injuries sustained by blood vessels that are in the tendon
sheath cause the formation of a hematoma. The resultant

105

clot activates the release of various chemotactic factors such

as vasodilators and proinflammatory molecules that attract
inflammatory cells from the surrounding tissue. Erythrocytes,
platelets, neutrophils, monocytes, and macrophages migrate
to the wound site where the clot, cellular debris, and foreign
body matter are engulfed and resorbed by phagocytosis.
Fibroblasts recruited to the site begin to synthesize various
components of the extracellular matrix.37 Angiogenic factors
are released during this phase and initiate the formation of a
vascular network.38 These processes include an increase in
DNA and in ECM, which establishes continuity and partial
stability at the site of injury.
Proliferative Stage
The continued recruitment of fibroblasts and their
rapid proliferation at the wound site are responsible for
the synthesis of collagens, proteoglycans, and other
components of the ECM. These components are
initially arranged in a random manner within the
ECM, which at this point is composed largely of type
III collagen.39 An extensive blood vessel network is
present, and the wound has a scar-like appearance.40
At the end of the proliferative stage, the repair tissue is
highly cellular and contains relatively large amounts of
water and an abundance of ECM components.
Remodeling Stage
Remodeling begins 6 8 weeks after injury. This phase is
characterized by a decrease in cellularity, reduced matrix
synthesis, decrease in type III collagen, and an increase in
type I collagen synthesis. Type I collagen fibers are
organized longitudinally along the tendon axis and are
responsible for the mechanical strength of the regenerate
tissue.41 During the later phases of remodeling, interactions
between the collagen structural units lead to higher tendon
stiffness and consequently greater tensile strength; however,
the repair tissue never achieves the characteristics of normal
tendon. Two distinct models have been proposed to explain
the mechanism of tendon healing.
Extrinsic healing: One hypothesis is that fibroblasts and
inflammatory cells move from the periphery or external
tissue sources to invade the healing site and initiate, and later
promote, repair and regeneration. This process includes the
initial formation of adhesions and requires a well-established
vascular network for the tissue to heal effectively.
Intrinsic healing: Intrinsic healing occurs through a
mechanism that entails the migration and proliferation of
cells from the endotenon and epitenon into the injury site;
these cells establish an extracellular matrix and an internal
neovascular network.
In most cases, both mechanisms are involved in the
healing phenomenon that is dependent on several factors,
including tendon location, extent of trauma, and
postoperative motion. The extrinsic mechanism, activated
earlier than the intrinsic mechanism, is responsible for the

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TENDON DEVELOPMENT, REPAIR, AND REGENERATION

FIGURE 3: Stages of tendon healing after midsubstance injury. GAG, glycosaminoglycans.

formation of adhesions that occur initially, the disorganized

collagen matrix with high cellularity, and high water content
of the injury site. By contrast, the intrinsic mechanism is
responsible for the reorganization of the collagen fibers and
maintenance of fibrillar continuity.
MOLECULAR MECHANISMS
During tendon repair, several growth factors are
involved in the activation and regulation of the cellular
responses. These factors or cytokines bind to specific
receptors that are present on the cell surface and
activate specific signaling events within the cell. This
initiates a cascade of pathways leading to the
transcription of specific regulatory genes. The
initiation or release of these factors is stimulated by
cells that are located at the site of injury and, during
the remodeling phase, by mechanical loading of the
injured tendon (Table 1).
Transforming growth factor- (TGF-) is a product of
most cells that are involved in the healing process; its 3
isoforms give rise to distinct spatial responses leading to its
diverse effects that regulate several events. During the initial
inflammatory phase after trauma, TGF- expression is
elevated and stimulates cellular migration and proliferation,
as well as interactions within the repair zone.42 Synthesis of
collagen type I and collagen type III is increased greatly
during the later phases. One of the isoforms of the growth
factor, TGF-1, is responsible for the initial scar tissue that
forms to establish tissue continuity at the wound site. In the
later phases of wound healing, increased expression of TGF1 leads to scar proliferation and reduced functionality.

Transforming growth factor-3 acts as a negative regulator

of scarring at the wound site.43,44 Transforming growth
factor- also serves to regulate the synthesis of collagen in
tendon mechanically during physical exercise.45
During the initial repair process and the inflammatory
phase, upregulation of growth factors and cytokines such as
insulin-like growth factor-1 (IGF-1) stimulate the
migration and proliferation of fibroblasts and
inflammatory cells to the wound site.46,47 Insulin-like
growth factor-1 may be stored as an inactive precursor
protein in normal tendon and, upon injury, enzymes
release the growth factor to exert its biological activity.
During the later phases such as remodeling, IGF-1
stimulates synthesis of collagen and other extracellular
matrix components; studies in vitro have shown that the
effects of IGF-1 on matrix metabolism are dose
dependent.48 50 Investigations with equine flexor tendon
injury models have shown that both cell proliferation and
collagen content increase on treatment with IGF-1.
These changes are accompanied by increased stiffness in
the treated tendon.51
Platelet derived growth factor (PDGF) induces the
expression of other growth factors such as IGF-1
during the initial repair phase. In addition, the delivery
of PDGF to tendon injuries in animal models increases
cell proliferation and stimulates the synthesis of
collagen and other ECM components in a dosedependent manner during the remodeling phase.5256
Some studies have shown that a phased delivery of
PDGF over a longer duration may be desirable to
obtain repair that leads to a regenerate tissue that is

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107

TABLE 1: Events During Tendon Repair*

Repair Phase
Inflammatory

Proliferative

Remodeling

Activity

Growth Factor
8082

Stimulates recruitment of fibroblasts and inflammatory cells

to the injury site

IGF-1

Regulation of cell migration

Expression and attraction of other growth factors (eg, IGF-1)
Angiogenesis
Cell proliferation (DNA synthesis)

TGF-42,8386
PDGF56,87,88
VEGF, bFGF6163,8992
IGF-1 and PDGF, TGF-, bFGF,
GDF-5, -6, and -76870,72,74
IGF-1 and PDGF, bFGF
TGF-, bFGF
TGF-, GDF-5, -6, and -7
IGF-1
TGF-
TGF-, GDF-5, -6, and -7

Stimulates synthesis of collagen and ECM components

Stimulates cell-matrix interactions
Collagen type III synthesis
ECM remodeling
Termination of cell proliferation
Collagen type I synthesis

*Tendon repair phases with biological characteristics and ensuing molecular events that are regulated by several cytokines or growth factors.

TABLE 2: Genes Involved With Tendon Development and Repair

Gene
Scleraxis72,9397
Tenomodulin96,98
Tenascin99
Collagen III41,100,101
Collagen I1,14,102,103
Decorin and aggrecan84,104
Smad8105

Function in Development, Repair, and Tissue Regeneration

Transcription factor specifically detected in tendon cell precursor populations and
selectively expressed in later stages
Regulators of cell proliferation, differentiation, and collagen fibril maturation
ECM protein evident during embryonic and tendon development
Early ECM collagen
Mature and highly organized collagen fibrils
Proteoglycan interactions modulating collagen fibril orientation and alignment
Tenocyte differentiation, phenotype modulation, and intracellular signaling

functionally closer to normal tendon.57,58 Experiments

conducted in vivo and in vitro attest to the mitogenic
activity of basic fibroblast growth factor (bFGF), a
potent factor that is involved in cell migration and
angiogenesis in addition to cell proliferation.59 Basic
fibroblast growth factor has been immunolocalized
during tendon repair and is expressed by fibroblast and
inflammatory cells.60 Wound healing models showed
distinctly faster wound closure on treatment with
increasing doses of bFGF.61 63 In this regard, bone
marrow stromal cells (BMSCs) treated with low doses
of bFGF have exhibited increased cell proliferation and
subsequent expression of specific extracellular matrix
components suggesting a potential role for
mesenchymal cells from marrow in tendon
regeneration.64
Vascular endothelial growth factor (VEGF) is critical for
neovascularization,65 and in the later phases, VEGF is

essential to the establishment and maintenance of the

vasculature present in the endotenon and epitenon.
Postoperatively, VEGF expression in healing tendons shows
a biphasic expression by a majority of the cells within the
repair site.66,67
Delivery of bone morphogenetic protein (BMP) -12,
-13, and -14 (also known as growth/differentiation factor
[GDF] -7, -6, and -5 or cartilage derived morphogenetic
protein [CDMP] -3, -2, and -1, respectively) to ectopic sites
leads to the formation of tendon-like connective tissue. In
animal models, treatment of tendon injuries with GDFs also
increases tendon callus. Growth/differentiation factors
regulate the synthesis of ECM components and expression
of collagen type I and collagen type III.68 74 These
polypeptide factors regulate the expression of specific genes
that are found in common among tendons and ligaments,
and the expression of these genes serve as markers of
tendinogenesis (Table 2).

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TENDON DEVELOPMENT, REPAIR, AND REGENERATION

TENDON INJURY ANIMAL MODEL

The development of biomaterials for orthopedic applications
and the discovery of growth factors that influence tendon
repair have influenced the approaches for the treatment of
tendon injuries. In addition, biodegradable materials that
may be implantable as a medical device to enhance tissue
repair or regeneration require rigorous testing in order to
establish the efficacy of these new therapeutic techniques.
The combination of novel biomaterials with the emerging
techniques of gene transfer and therapy further increase the
possibilities of restoring tendon to its normal function. In
concert with these developing techniques is the need for in
vitro evaluation of parameters to establish biocompatibility,
mechanical properties, cell proliferation, biochemical analysis
of tendon extracellular matrix and gene expression, and to
extend these measurements to an appropriate animal model
in vivo before applications to clinical situations.7577
Although specimens from cadavers have helped develop
techniques for a limited number of research problems, use of
cadaveric parts is not suitable for investigations of various
pathologic states. Some therapies do not reach the point of
clinical trials because baseline information on the potential
effect on humans is lacking.
It is widely accepted that there is no model in which all
potential therapies may be tested appropriately; however, it has
become essential to have an animal model matched to the
clinical pathology prior to initiating a clinical trial. When
selecting an appropriate animal model, the salient criteria to
consider are a closely matched anatomic structure and the ease
with which the treatment can be translated to a clinical
setting.78 A study of adhesions formed after injury to the flexor
tendon in the primate was found to have the closest
resemblance to humans in both surgical technique and physical
attributes of the matching tissues and organs.79 Use of dogs and
chickens has been ruled out primarily because their physical and
anatomic features do not match the human anatomy. This is
essential for research translation from an animal model to the
human situation. In short, testing materials, biological factors,
and surgical techniques in an animal model that mimics the
pathogenic condition in humans is ideal because it will facilitate
research translation to humans. Murine models that simulate
various disease states, such as genetic disorders, growth factor
deficiencies, cancers, and immunodeficiency are available to
many investigators. Animal models have given a major boost to
the design of research tools and are available for the
development and validation of novel therapies prior to human
trials. These models are used to test procedures quantitatively
and to determine the ease and effectiveness of surgical
procedures, and they allow for statistically significant studies in
mice, rats, and rabbits. In addition, larger animals, such as goats,
sheep, as well as porcine and equine models, have been utilized
in appropriate circumstances. The choice of the animal model is
also determined by the outcomes sought by the investigators.
Most animal models are appropriate for the determination of
histology, cell proliferation, and biochemical analysis in order to
determine the effectiveness of surgical or therapeutic treatment

procedures. The need to have a technically reproducible and

mechanically stable tendon injury model is paramount to the
ultimate utility of the animal model. In addition, the availability
of techniques that will measure the strength of the regenerate
tissue is necessary with most musculoskeletal components.
These considerations set the lower limit to the anatomic size
and morphologic features within the experimental model. In
choosing an animal model, an important consideration is the
ability to compare results with the existing literature to better
assess the effects of a therapy that leads to the desired outcome.
EVOLVING TREATMENT OPTIONS
Although our understanding of tendon biology and the
biological processes that regulate repair have progressed
tremendously, many challenges need to be addressed to
bring about a successful treatment strategy. Progress in
deciphering how the temporal and spatial biochemical cues
effect repair and regenerate tissue, combined with
development of a suitable biomaterial that will provide
mechanical support, shows great promise in formulating a
tissue-engineering treatment option. Growth factors
regulate the repair process in a spatial and temporal
manner; however, the exact mechanisms on the
downstream pathways are lacking. Recent studies have
shown that growth factors can modulate stromal cells into
specific lineages. Recently, adipose-derived stromal cells
have been shown to differentiate into multiple lineages
under appropriate chemical cues. In addition,
subpopulations exist within the stromal cells that exhibit
phenotypic and surface markers leading to a specific cell
type. Treatment options involving growth factors, alone
or in combination with a stromal population, may form
functional repair or regenerate tendon faster than existing
treatment modalities. The delivery of necessary factors at
the required dosages in a temporal and spatial pattern
over the repair phase is critical to a successful treatment.
The appropriate delivery option may deliver and maintain
suitable stromal cells at the repair site to effect a faster
repair process. The repair or regenerate functional tissue
must form in synchronization with degradation of the
delivery vehicle. Depending on the application,
biomaterials can be modulated to have the desired
property (factor delivery and biomimetic). Tendons and
ligaments must be loaded in tension during the repair
phase to prevent scarring and adhesion formation with
the surrounding tissues. The biomaterial must transmit
tensile forces from muscle to bone to support digit
movement after treatment. Recent studies have
investigated the potential of polymeric scaffolds for
musculoskeletal applications. The choice of biomaterial
and processing technique can be used to modulate the
physical properties of the tissue-engineering implant, and
nanoarchitecture on the scaffold surface elicits ECM
deposition and organization. Treatment strategies using
these various parameters are extremely promising for
tendon tissue-engineering applications. The challenge is
to consolidate the progress in various areas (role of

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chemical cues, biomechanics, biomaterials, and suitable

stromal cells) to overcome the current obstacles in
achieving a functional repair or regenerate tendon.
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