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migrate into. These cells are the starting point
for formation of a fibrovascular scar which can
remodel into relatively normal ligament tissue.
Certainly, an injured ACL bleeds as well;
however, enzymes in the synovial fluid prevent
formation of a clot or a bridging scaffold in the
ACL wound site. A fibrin clot is hardly formed
in a post-traumatic intraarticular milieu. Quite
contrary, due to enzymes in the synovial fluid,
a rapid clot breakdown occurs [1]. This lack of
a provisional scaffold bridging a torn ACL
might be the reason for a healing failure.
In consequence, developing a sponge-like
scaffold to absorb blood and stabilize the clot
within the ACL wound site in the synovial fluid
environment may facilitate healing of the
repaired ACL.
In the same context, growth factors have also
gained a lot of traction in the treatment of soft
tissue injuries. A wide range of these factors,
such as insulin-like growth factor (IGF),
TGF-β, platelet-derived growth factor (PDGF),
vascular endothelial growth factor (VEGF),
broblast growth factor (FGF) and nerve
growth factor (NGF), have been used to try to
improve ligamentous and tendon tissue repair.
All of these factors stimulate type I collagen
production in ACL-derived cells
in vitro
,
except for insulin-like growth factor. Kobayashi
et al.
noted in an
in vivo
study that Fibroblast
Growth Factor 2 improved healing and
neovascularization of partially lacerated ACLs
in canines. Also, injections of recombinant
human hepatocyte growth factor and TGF- β1
yielded improved biomechanical results and
histological healing properties in a rabbit
model [4]. However, to deliver these growth
factors to a localized wound site of a torn ACL
in vivo
remains a major barrier for effective use
of these purified factors.
Another source of many of these growth
factors, platelet-rich-plasma (PRP), has been
the center of attention as a novel, non-invasive
treatment for sports related injuries. Although
PRP is capable of forming a clot, its use to
stimulate ACL graft healing has delivered
mixed results. In a porcine model using a
transected ACL, when used alone, PRP did not
stimulate functional healing [11]. A fact that
may explain the different results in using PRP
is that the main structural protein in clotted
PRP is fibrin. After an injury, the synovial fluid
contains a large amount of fibrin-degrading
enzymes. Therefore, the fibrin-based PRP clot
may be prematurely dissolved in the post-
traumatic or postsurgical environment. This
situation could be the reason why PRP on its
own fails to stimulate tissue healing even
though it is capable of delivering stimulatory
growth factors to the wound site. In
consequence, carriers to maintain the PRP at
the tear of the ACL and protect it from being
washed out of the wound site have been
developed. A substance more resistant to
degradation by plasmin is a copolymer formed
of collagen mixed with fibrin [1]. Furthermore,
collagen activates platelets in a sustained
fashion and releases platelet-associated factors
over a period of 10 to 14 days. In contrast,
platelets activated by thrombin are released
physiologically within the first few hours. Thus
collagen has been explored as a carrier for
platelets for ACL repair.
Unlike a primary suture repair alone, an ACL
repair supplemented with a collagen-PRP
biomaterial improved the biomechanical
properties of the repaired ACL in an
in vivo
pig
model after four weeks [11]. Further
experiments demonstrated that the use of
whole blood was more effective than using
PRP to stimulate wound healing of the ACL.
While neither the collagen scaffold itself nor
PRP alone was found to be effective in
promoting ACL healing or repair, the
combination of blood, collagen scaffold and
suture stent in the novel technique of Bridge-
Enhanced ACL Repair (fig. 1) led to
biomechanical properties of the repaired ACL
equivalent to those of an ACL reconstruction
after 3, 6, and 12 months of healing in the
porcine model [10]. Moreover, the bridge-
enhanced ACL repair significantly reduced the
amount of cartilage damage usually seen
12 months after an untreated ACL transection
or an ACL reconstruction [5, 6]. These findings
might suggest that a bridge-enhanced repair of
the ACL protects the cartilage against early
onset of osteoarthritis, which in contrast is