Repairing mechanically-stressed
tissues, such as tendons, creates a challenging situation in the orthopedic
surgical field. Conventionally, sutures work poorly for this application as the
strength requirements for holding the tendon in place are very high and the
interface between the suture and the tendon creates a weak point which is prone
to failure. Genipin is a naturally-derived crosslinking material which can act
to potentially reinforce tissues. Recently, researchers from Balgrist
University and ETH Zurich (Switzerland) used PLGA (PolyVivo AP081) from
PolySciTech (www.polyscitech.com) to develop
and test sutures loaded with Genipin for tendon repair. This research holds promise
to improve orthopedic surgical outcomes and healing for tendon-repair
procedures. Read more: Camenzind, Roland S., Timo O. Tondelli, Tobias Goetschi,
Claude Holenstein, and Jess G. Snedeker. "Can Genipin-coated Sutures
Deliver a Collagen Crosslinking Agent to Improve Suture Pullout in Degenerated
Tendon? An Ex Vivo Animal Study." Clinical Orthopaedics and Related
Research 476, no. 5 (2018): 1104-1113. https://journals.lww.com/clinorthop/Fulltext/2018/05000/Can_Genipin_coated_Sutures_Deliver_a_Collagen.34.aspx
“Background The
suture-tendon interface is often the weakest link in tendon-to-tendon or
tendon-to-bone repair. Genipin is an exogenous collagen crosslink agent derived
from the gardenia fruit that can enhance suture force to failure of the
tendon-suture interface. Viable methods for intraoperative clinical delivery of
genipin could be of clinical utility, but to our knowledge have not yet been
extensively studied. Questions/purposes The purposes of this study were (1) to
evaluate whether sutures precoated with genipin can augment the suture-tendon
interface to improve force to failure, stiffness, and work to failure in
healthy and degenerated tendons; and (2) to determine the effect of genipin on
the extent and distribution of crosslinking. Methods Single-stitch suture
pullout tests were performed ex vivo on 25 bovine superficial digital flexor
tendons. To assess effects on native tissue, one group of 12 tendons was cut in
proximal and distal halves and randomized to treatment (n = 12) and control
groups (n = 12) in a matched-pair design. One simple stitch with a loop with
either a normal suture or genipin-coated suture was applied to tendons in both
groups. To simulate a degenerative tendon condition, a second group of 13
tendons was cut in proximal and distal halves, injected with 0.2 mL of
collagenase D (8 mg/mL) and incubated for 24 hours before suturing with either
a genipin-coated suture (n = 13) or their matched controls (n = 13). Sutures
from all groups then were loaded to failure on a universal materials testing
machine 24 hours after suturing. Suture pullout force, stiffness, and work to
failure were calculated from force-displacement data and compared between the
groups. Additionally, fluorescence was measured to determine the degree of
crosslinking quantitatively and a qualitative analysis of the distribution
pattern was performed by microscopy. Results In healthy tendon pairs, the
median maximum pullout force was greater with genipin-coated sutures than with
control sutures (median, 42 N [range, 24–73 N] versus 29 N [range, 13–48 N];
difference of medians, 13 N; p = 0.003) with corresponding increases in the
required work to failure (median, 275 mJ [range, 48–369 mJ] versus 148 mJ
[range, 83–369 mJ]; difference of medians, 127 mJ; p = 0.025) but not stiffness
(median, 4.1 N/mm [range, 2.3–8.1 N/mm] versus 3.3 N/mm [range, 1.1–9.6 N/mm];
difference of medians, 0.8 N/mm; p = 0.052). In degenerated tendons, median
maximum pullout force was greater with genipin-coated sutures than with control
sutures (median, 16 N [range, 9-36 N] versus 13 N [range, 5-28 N]; difference
of medians, 3 N; p = 0.034) with no differences in work to failure (median, 75
mJ [range, 11–249 mJ] versus 53 mJ [range, 14–143 mJ]; difference of medians,
22 mJ; p = 0.636) or stiffness (median, 1.9 N/mm [range, 0.7–13.4 N/mm] versus
1.6 N/mm [range, 0.5–5.6 N/mm]; difference of medians, 0.3 N/mm; p = 0.285).
Fluorescence was higher in tendons treated with genipin-coated sutures compared
with the control group, whereas higher fluorescence was observed in the treated
healthy compared with the degenerated tendons (difference of means -3.16;
standard error 1.08; 95% confidence interval [CI], 0.97–5.34; p = 0.006/healthy
genipin: mean 13.04; standard error 0.78; 95% CI, 11.47-14.62; p <
0.001/degenerated genipin: mean 9.88; SD 0.75; 95% CI, 8.34-11.40; p <
0.001). Conclusions Genipin-coated sutures improved force to failure of a
simple stitch at the tendon-suture interface in healthy and degenerated tendons
in an ex vivo animal model. Fluorescence was higher in tendons treated with
genipin-coated sutures compared with the control group. Clinical Relevance A
genipin-coated suture represents a potential delivery vehicle for exogenous
crosslink agents to augment suture retention properties. In vivo animal studies
are the next logical step to assess safety and efficacy of the approach.”
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