Zhao, Chunfeng

The intrinsic healing following tendon injury is ideal, in which tendon progenitor cells proliferate and migrate to the injury site to directly bridge or regenerate tendon tissue. However, the mechanism determining why and how those cells are attracted to the injury site for tendon healing is not understood. Since the tenocytes near the injury site go through apoptosis or necrosis following injury, we hypothesized that secretions from injured tenocytes might have biological effects on cell proliferation and migration to enhance tendon healing. Tenocyte apoptosis was induced by 24 h cell starvation. Apoptotic body-rich media (T-ABRM) and apoptotic body-depleted media (T-ABDM) were collected from culture media after centrifuging. Tenocytes and bone marrow-derived stem cells (BMDSCs) were isolated and cultured with the following four media: (1) T-ABRM, (2) T-ABDM, (3) GDF-5, or (4) basal medium with 2% fetal calf serum (FCS). The cell activities and functions were evaluated. Both T-ABRM and T-ABDM treatments significantly stimulated the cell proliferation, migration, and extracellular matrix synthesis for both tenocytes and BMDSCs compared to the control groups (GDF-5 and basal medium). However, cell proliferation, migration, and extracellular matrix production of T-ABRM-treated cells were significantly higher than the T-ABDM, which indicates the apoptotic bodies are critical for cell activities. Our study revealed the possible mechanism of the intrinsic healing of the tendon in which apoptotic bodies, in the process of apoptosis, following tendon injury promote tenocyte and stromal cell proliferation, migration, and production. Future studies should analyze the components of the apoptotic bodies that play this role, and, thus, the targeting of therapeutics can be developed.

Background: The stability of a suture knot construct has been realized as an important parameter that affects the strength of flexor tendon repairs. A novel 2-strand-overhand-locking (TSOL) knot, which is not commonly used in the clinical setting, recently was reported to increase repair strength and to decrease tendon gliding resistance in a 2-strand repair technique. The purpose of the present study was to investigate the effect of the TSOL knot on tendon repair strength and gliding resistance compared with a typical surgical knot in both 2-strand and 4-strand repair techniques using an in vitro turkey flexor tendon model. Methods: Sixty flexor digitorum profundus tendons from the long digit of the turkey foot were divided evenly into 4 groups and repaired with the following techniques: (1) a 2-strand modified Pennington repair with a square knot, (2) a 2-strand modified Pennington repair with a TSOL knot, (3) a 4-strand grasping cruciate repair with a square knot, and (4) a 4-strand grasping cruciate repair with a TSOL knot. Repaired tendons were tested for failure mode, gliding resistance, and repair strength at failure. Results: The repair strength and stiffness of the 4-strand repairs were significantly higher than those of the 2-strand repairs, regardless of knot type (p < 0.05). The repair strength at failure of the TSOL knot was significantly greater than that of the square knot in 2-strand repairs (p < 0.05) but not in 4-strand repairs. The gliding resistance of the TSOL knot was significantly decreased compared with that of the square knot in both 2-strand and 4-stand repairs (p < 0.05). With regard to failure mode, the TSOL knot was less likely to fail due to knot unravelling. Conclusions: In this in vitro biomechanical study involving the use of turkey flexor tendons to compare gliding resistance and repair strength characteristics for knot-inside 2 and 4-strand repairs, the TSOL knot was associated with decreased repaired tendon gliding resistance, regardless of the number of strands used. Although the TSOL knot also increased the repair strength, the difference was only significant when 2-strand repairs were used. The results of our study support the use of the TSOL knot in the clinical setting of flexor tendon repair using 2 or 4-strand, knot-inside methods. Clinical Relevance: In surgical repair of flexor tendons, there is substantial interest in maximizing strength while minimizing friction. This study shows the potential utility of the TSOL knot to increase repair strength while decreasing gliding resistance, particularly in 2-strand repairs.

AbstractReducing 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 the ex vivo model, FDP tendons were randomly divided into three groups: FDP tendon repair alone group (Control), Tisseel patch alone group, and the Tisseel plus PEP (TEPEP) patch group. Following 4 weeks of tissue culture, the failure load, stiffness, histology, and gene expression of the healing tendon were evaluated. Transmission electron microscopy revealed that in 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 2 weeks. The failure strength of the 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 reverse transcription polymerase chain reaction showed that TEPEP patch increased the expression of collagen type III, matrix metallopeptidase 2 (MMP2), MMP3, MMP14, and reduced the expression of transforming growth factor β1, interleukin 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 formation of type III collagen.