Advances in the Canine Cranial Cruciate Ligament, 2nd edition

Regenerative Medicine and Cranial Cruciate Ligament Repair 373

in a porcine model of CrCL repair at 15 weeks
after surgery (Proffenet al. 2015). Thus, the cur-
rent evidence supports the use of whole autol-
ogous blood in bridge-enhanced CrCL repair
(Murray & Fleming 2013).

Non-invasive and non-destructive
assessment of graft properties

A potentially major clinical issue with CrCL
repair is the lack of a non-invasive and
non-destructive assessment of graft proper-
ties. Advances in magnetic resonance imaging
sequences have shown ways to assess ligament
properties using T2∗mapping. Ligament vol-
ume and T2 relaxation parameters have been
shown to correlate with stiffness (R^2 =0.85) and
strength (R^2 =0.67) in a porcine model follow-
ing CrCL reconstruction (Fleminget al.2011),
and an algorithm to predict CrCL graft strength
from T2∗relaxometry has recently been vali-
dated (Figure 45.2) (Bierceviczet al. 2013).

Can arthritic degeneration be stopped?

Beyond the functional losses from a torn CrCL,
a major concern is the accelerated onset of
arthritis. One key to unlocking this complex
issue is to define the events occurring after the
initial trauma. In the CrCL-deficient minipig,
an immediate upregulation of catalytic protein
mRNA can be seen across cartilage, syn-
ovium, and ligament cells after ligament injury
(Haslauer et al. 2013). Further research has
shown that treatment of the ligament injury

using a collagen-based tissue engineering scaf-

fold can compensate for this by upregulation of

anabolic protein transcription (Haslaueret al.

2014). It has also been shown recently that injec-

tion of an ECM scaffold and blood composite

in rats, without specific CrCL treatment, will

reduce the rate of post-traumatic OA after CrCL

transection (Proffenet al.2016) (Figure 45.3).

The immediate injection of triamcinolone

after CrCL transection has also been found

to reduce the amount of synovitis and subse-

quent collagen degradation (Siekeret al. 2016).

Most significantly, in a 1-year study of bridge-

enhanced CrCL repair (Figure 45.4) in minipigs,

those animals receiving bridge-enhanced CrCL

repair with an ECM scaffold and autologous

blood demonstrated a substantially lower rate

of OA compared to those receiving an intra-

articular CrCL reconstruction (Murray & Flem-

ing 2013) (Figure 45.5). These data demonstrate

that a regenerative treatment of the CrCL may

allow for ligament repair but also may have the

potential effect of suppressing the degradative

synovial response and protecting the articular

cartilage.

Additional factors affecting CrCL

healing

What other factors outside the procedure can

affect the outcome of regenerative CrCL treat-

ment? One important factor may be the tim-

ing of surgical treatment post-injury. Studies

have shown that delaying attempts at regen-

erative treatment will result in worse out-

comes, most likely due to the ongoing retraction

(^2000) Standard Error of Estimate = 216.1 N
2000
1500
1500
1000
1000
Actual Maximum Load (N)
Predicated Maximum Load (N)
500
500
0
0
Figure 45.2 Actual maximum load versus
predicted maximum load for both 15- and
52-week time points, calculated using volume
and median grayscale value. Source: Biercevicz
et al. 2013. Reproduced with permission from
SAGE Publications.