A novel engineered purified exosome product patch for tendon healing: An explant in an ex vivo model

Authors: 
Guidong Shi, Yicun Wang, Zhanwen Wang, Andrew R Thoreson, Daniel S Jacobson, Peter C Amadio, Atta Behfar, Steven L Moran, Chunfeng Zhao
J Orthop Res. 2020 Sep 16. doi: 10.1002/jor.24859.

Reducing tendon failure after repair remains a challenge due to its poor intrinsic healing ability. The purpose of this study is to investigate the effect of a novel tissue-engineered purified exosome product (PEP) patch on tendon healing in a canine ex vivo model.

Lacerated flexor digitorum profundus (FDP) tendons from three canines' paws underwent simulated repair with Tisseel patch alone or biopotentiated with PEP. For ex vivo model, FDP tendons were randomly divided into 3 groups: FDP tendon repair alone group (Control), Tisseel patch alone group, and Tisseel plus PEP (TEPEP) patch group. Following four weeks of tissue culture, the failure load, stiffness, histology and gene expression of the healing tendon were evaluated.

The transmission electron microscopy (TEM) revealed that exosomes of PEP the diameters ranged from 93.70 to 124.65 nm, and the patch release test showed this TEPEP patch could stably release the extracellular vesicle over two weeks. The failure strength of tendon in the TEPEP patch group was significantly higher than that of the Control group and Tisseel alone group. The results of histology showed that the TEPEP patch group had the smallest healing gap and the largest number of fibroblasts on the surface of the injured tendon. Quantitative RT-PCR showed that TEPEP patch increased the expression of COL3, MMP2, MMP3, MMP14, and reduced the expression of TGF-beta1, IL-6.

This study shows that the TEPEP patch could promote tendon repair by reducing gap formation and inflammatory response, increasing the activity of endogenous cells and the formation of type III collagen.