Purpose
This study aimed (1) to confirm the maintenance of the extracellular vesicles (EVs)
delivered via injectable collagen at the application site, and (2) to evaluate the
effect of EVs derived from the human umbilical cord-derived mesenchymal stem cells
and loaded in an injectable collagen gel after rotator cuff repair (RCR).
Methods
Rabbits (n = 20) were assigned to normal (N), repair-only (R), and those administered
with injectable collagen after repair (RC), and EV-laden injectable collagen after
repair (RCE) groups. The EVs isolated by ultra-centrifugation from the human umbilical
cord-derived mesenchymal stem cells spent medium were mixed with collagen and administered
accordingly. After 12 weeks, the rabbits were sacrificed to evaluate the healing of
the bone-to-tendon junction and the fatty degeneration of muscle. Histomorphometric
scoring for bone–tendon interface, fatty infiltration (%), and biomechanical tests
were performed. Separately, groups of 3 rabbits were assigned to 3 different time
points to evaluate maintenance of green fluorescence-labeled EVs with injectable collagen
via tracking on the bursal side of the rotator cuff (3 groups: 3 days, 2, and 4 weeks).
Results
The EVs delivered by injectable collagen remained until 4 weeks at the bursal side
of the cuff tissue. The RCE group showed a significantly greater histomorphometric
total score (P < .001, and P = .013, respectively) and significantly lower fatty degeneration than the RC and
R groups (P = .001, and P = .013, respectively). The biomechanical tests revealed significant growing trends
in load-to-failure and stiffness (P = .002, and P = .013, respectively), in the R, RC, RCE, and N groups.
Conclusions
EVs mounted in injectable collagen remained at the repair site for at least 4 weeks
after application. Furthermore, they effectively promote bone-to-tendon healing via
collagen maturation in bone–tendon interface and preventing fatty degeneration of
rotator muscle after RCR as compared with collagen-only or repair-only groups.
Clinical Relevance
The combination of collagen with EVs significantly promotes rotator cuff healing demonstrating
potential clinical application during partial rotator cuff tear or after RCR.
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Article Info
Publication History
Published online: January 15, 2022
Accepted:
January 7,
2022
Received:
August 17,
2021
Footnotes
See commentary on page 2154
The authors report the following potential conflicts of interest or sources of funding: This research was supported by National Research Foundation of Korea , South Korea Grant funded by the Korean Ministry of Education (no. 2018R1D1A1A0208602513 ) and the Asan Institute for Life Sciences , Asan Medical Center , Seoul, Korea (no. 2021IP-0042 ). This research was supported by the Korean Fund for Regenerative Medicine funded by Ministry of Science and ICT, and Ministry of Health and Welfare ( HH21C0001 , Republic of Korea). Full ICMJE author disclosure forms are available for this article online, as supplementary material.
Hyojune Kim, M.D., and In Kyong Shim, Ph.D., are co-first authors.
Identification
Copyright
© 2022 by the Arthroscopy Association of North America
