Citations

The objective of this study was to examine the effect of pulling angle on time-zero mechanical properties of intact infraspinatus tendon or infraspinatus tendon repaired with the modified Mason-Allen technique in a canine model in vitro. Thirty-six canine shoulder samples were used. Twenty intact samples were randomly allocated into functional pull (135°) and anatomic pull (70°) groups (n = 10 per group). The remaining sixteen infraspinatus tendons were transected from the insertion and repaired using the modified Mason-Allen technique before being randomly allocated into functional pull or anatomic pull groups (n = 8 per group). Load to failure testing was performed on all specimens. The ultimate failure load and ultimate stress of the functional pulled intact tendons were significantly lower compared with anatomic pulled tendons (1310.2 ± 167.6 N vs. 1687.4 ± 228.2 N, p = 0.0005: 55.6 ± 8.4 MPa vs. 67.1 ± 13.3 MPa, p = 0.0334). For the tendons repaired with the modified Mason-Allen technique, no significant differences were observed in ultimate failure load, ultimate stress or stiffness between functional pull and anatomic pull groups. The variance of pulling angle had a significant influence on the biomechanical properties of the rotator cuff tendon in a canine shoulder model in vitro. Load to failure of the intact infraspinatus tendon was lower at the functional pulling position compared to the anatomic pulling position. This result indicates that uneven load distribution across tendon fibers under functional pull may predispose the tendon to tear. However, this mechanical character is not presented after rotator cuff repair using the modified Mason-Allen technique.

Background: Flexor digitorum profundus (FDP) tendon injury is common in hand trauma, and flexor tendon reconstruction is one of the most challenging procedures in hand surgery because of severe adhesion that exceeds 25% and hinders hand function. The surface properties of a graft from extrasynovial tendons are inferior to those of the native intrasynovial FDP tendons, which has been reported as one of the major causations. Improved surface gliding ability of the extrasynovial graft is needed. Thus, this study used carbodiimide-derivatized synovial fluid and gelatin (cd-SF-gel) to modify the surface of the graft, thus improving functional outcomes using a dog in vivo model. Methods: Forty FDP tendons from the second and fifth digits of 20 adult women underwent reconstruction with a peroneus longus (PL) autograft after creation of a tendon repair failure model for 6 weeks. Graft tendons were either coated with cd-SF-gel (n = 20) or not. Animals were euthanized 24 weeks after reconstruction, and digits were collected after the animals were euthanized for biomechanical and histologic analyses. Results: Adhesion score (cd-SF-gel, 3.15 ± 1.53; control, 5 ± 1.26; P < 0.00017), normalized work of flexion (cd-SF-gel, 0.47 ± 0.28 N-mm/degree; control, 1.4 ± 1.45 N-mm/degree; P < 0.014), and distal interphalangeal joint motion (cd-SF-gel, 17.63 ± 6.77 degrees; control, 7.07 ± 12.99 degrees; P < 0.0015) in treated grafts all showed significant differences compared with nontreated grafts. However, there was no significant difference in repair conjunction strength between the two groups. Conclusion: Autograft tendon surface modification with cd-SF-gel improves tendon gliding ability, reduces adhesion formation, and enhances digit function without interfering with graft-host healing. Clinical Relevance Statement: The authors demonstrate a clinically relevant and translational technology by using the patient’s own synovial fluid to “synovialize” an autologous extrasynovial tendon graft to improve functional outcomes following flexor tendon reconstruction.

Background: Nerve injuries can result in detrimental functional outcomes. Currently, autologous nerve graft offers the best outcome for segmental peripheral nerve injury. Allografts are alternatives, but do not have comparable results. This study evaluated whether plasma-derived exosome can improve nerve regeneration and functional recovery when combined with decellularized nerve allografts. Methods: The effect of exosomes on Schwann cell proliferation and migration were evaluated. A rat model of sciatic nerve repair was used to evaluate the effect on nerve regeneration and functional recovery. A fibrin sealant was used as the scaffold for exosome. Eighty-four Lewis rats were divided into autograft, allograft, and allograft with exosome groups. Gene expression of nerve regeneration factors was analyzed on postoperative day 7. At 12 and 16 weeks, rats were subjected to maximum isometric tetanic force and compound muscle action potential. Nerve specimens were then analyzed by means of histology and immunohistochemistry. Results: Exosomes were readily taken up by Schwann cells that resulted in improved Schwann cell viability and migration. The treated allograft group had functional recovery (compound muscle action potential, isometric tetanic force) comparable to that of the autograft group. Similar results were observed in gene expression analysis of nerve regenerating factors. Histologic analysis showed no statistically significant differences between treated allograft and autograft groups in terms of axonal density, fascicular area, and myelin sheath thickness. Conclusions: Plasma-derived exosome treatment of decellularized nerve allograft may provide comparable clinical outcomes to that of an autograft. This can be a promising strategy in the future as an alternative for segmental peripheral nerve repair. Clinical Relevance Statement: Off-the-shelf exosomes may improve recovery in nerve allografts.

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.

Soft tissue defects are common following trauma and tumor extirpation. These injuries can result in poor functional recovery and lead to a diminished quality of life. The healing of skin and muscle is a complex process that, at present, leads to incomplete recovery and scarring. Regenerative medicine may offer the opportunity to improve the healing process and functional outcomes. Barriers to regenerative strategies have included cost, regulatory hurdles, and the need for cell-based therapies. In recent years, exosomes, or extracellular vesicles, have gained tremendous attention in the field of soft tissue repair and regeneration. These nanosized extracellular particles (30–140 nm) can break the cellular boundaries, as well as facilitate intracellular signal delivery in various regenerative physiologic and pathologic processes. Existing studies have established the potential of exosomes in regenerating tendons, skeletal muscles, and peripheral nerves through different mechanisms, including promoting myogenesis, increasing tenocyte differentiation and enhancing neurite outgrowth, and the proliferation of Schwann cells. These exosomes can be stored for immediate use in the operating room, and can be produced cost efficiently. In this article, we critically review the current advances of exosomes in soft tissue (tendons, skeletal muscles, and peripheral nerves) healing. Additionally, new directions for clinical applications in the future will be discussed.

Background: Tendons are primarily acellular, limiting their intrinsic regenerative capabilities. This limited regenerative potential contributes to delayed healing, rupture, and adhesion formation after tendon injury. Purpose: To determine if a tendon’s intrinsic regenerative potential could be improved after the application of a purified exosome product (PEP) when loaded onto a collagen scaffold. Study Design: Controlled laboratory study. Methods: An in vivo rabbit Achilles tendon model was used and consisted of 3 groups: (1) Achilles tenotomy with suture repair, (2) Achilles tenotomy with suture repair and collagen scaffold, and (3) Achilles tenotomy with suture repair and collagen scaffold loaded with PEP at 1 × 10 12 exosomes/mL. Each group consisted of 15 rabbits for a total of 45 specimens. Mechanical and histologic analyses were performed at both 3 and 6 weeks. Results: The load to failure and ultimate tensile stress were found to be similar across all groups ( P ≥ .15). The tendon cross-sectional area was significantly smaller for tendons treated with PEP compared with the control groups at 6 weeks, which was primarily related to an absence of external adhesions ( P = .04). Histologic analysis confirmed these findings, demonstrating significantly lower adhesion grade both macroscopically ( P = .0006) and microscopically ( P = .0062) when tendons were treated with PEP. Immunohistochemical staining showed a greater intensity for type 1 collagen for PEP-treated tendons compared with collagen-only or control tendons. Conclusion: Mechanical and histologic results suggested that healing in the PEP-treated group favored intrinsic healing (absence of adhesions) while control animals and animals treated with collagen only healed primarily via extrinsic scar formation. Despite a smaller cross-sectional area, treated tendons had the same ultimate tensile stress. This pilot investigation shows promise for PEP as a means of effectively treating tendon injuries and enhancing intrinsic healing. Clinical Relevance: The production of a cell-free, off-the-shelf product that can promote tendon regeneration would provide a viable solution for physicians and patients to enhance tendon healing and decrease adhesions as well as shorten the time required to return to work or sports.

Abstract Rotator cuff injuries increase with age. The enthesis is the most frequent site of rotator cuff injury and degeneration. Understanding age‐related changes of the enthesis are essential to determine the mechanism of rotator cuff injuries, degeneration, and to guide mechanistically driven therapies. In this study, we explored age‐related cellular changes of the rotator cuff enthesis in young, mature, and aged rats. Here we found that the aged enthesis is typified by an increased mineralized zone and decreased nonmineralized zone. Proliferation, migration, and colony‐forming potential of rotator cuff derived cells (RCECs) was attenuated with aging. The tenogenic and chondrogenic potential were significantly reduced, while the osteogenic potential increased in aged RCECs. The adipogenic potential increased in RCECs with age. This study explores the cellular differences found between young, mature, and aged rotator cuff enthesis cells and highlights the importance of using age‐appropriate models, as well as provides a basis for further delineation of mechanisms and potential therapeutics for rotator cuff injuries.