In Situ-Forming Fibrin Gel Encapsulation of MSC-Exosomes for Partial-Thickness Rotator Cuff Tears in a Rabbit Model: Effectiveness Shown in Preventing Tear Progression and Promoting Healing.

Abstract

Current nonoperative treatments for partial-thickness rotator cuff tears (PTRCTs) have limited effectiveness in preventing tear progression or promoting tendon healing. This study aimed to establish a rabbit model using in situ-forming fibrin gel containing adipose stem cell-derived exosomes (ASC-Exos/fibrin) to treat PTRCTs. Fifty-six rabbits (112 shoulders) were included in this study and assigned to 4 groups: the control group (32 shoulders; PTRCTs without treatment), the fibrin group (32 shoulders; PTRCTs treated with fibrin gel), the ASC-Exo/fibrin group (32 shoulders; PTRCTs treated with ASC-Exos/fibrin), and the sham group (16 shoulders; sham surgery). Bilateral, 50%-thickness, bursal-side PTRCTs of 1 mm (depth) × 3 mm (width) × 5 mm (length) on the supraspinatus tendon were established by a number-11 scalpel blade, with accuracy of the measurement ensured by a digital vernier caliper. At 6 and 12 weeks postoperatively, gross observation, measurement of the thickness of residual supraspinatus tendons, and histological and biomechanical analyses were performed to analyze tendon repair. At 12 weeks postoperatively, the tendon thickness in the ASC-Exos/fibrin group (mean and standard deviation, 1.63 ± 0.19 mm) was significantly greater than in the control group (0.85 ± 0.09 mm) (p < 0.0001) and fibrin group (1.16 ± 0.17 mm) (p < 0.0001). The histological score in the ASC-Exos/fibrin group (6.25 ± 0.53) was significantly better than in the control group (11.38 ± 0.72) (p < 0.0001) and fibrin group (9.00 ± 0.54) (p < 0.0001). Overall, immunohistochemical staining of types-I and III collagen and biomechanical testing also showed ASC-Exos/fibrin to be more effective in repairing PTRCTs than fibrin alone and no treatment. Local administration of in situ-forming ASC-Exos/fibrin effectively facilitated the healing of bursal-side PTRCTs in rabbits. This approach may be a candidate for the nonoperative management of PTRCTs. Ultrasound-guided injection of ASC-Exos/fibrin may be a novel nonoperative strategy to treat PTRCTs.