Loading Mesenchymal Stem Cell–Derived Exosomes Into a Traditionally Designed Rotator Cuff Patch: A Potential Strategy to Enhance the Repair of Chronic Rotator Cuff Tear Associated With Degenerative Changes

Abstract

Background: Retraction and degenerative changes of chronic rotator cuff tears limit the healing capacity after routine surgical repair. Purpose: To fabricate a mesenchymal stem cell–derived exosome (MSC–Exos) loaded patch and evaluate the effect of this patch on the activity of rabbit tenocytes in vitro and on the repair of chronic rotator cuff tears associated with degenerative changes in vivo. Study Design: Controlled laboratory study. Methods: The MSC–Exos loaded patch was fabricated using a dynamic wet-spinning system. In the in vitro studies, the proliferation and migration activities of tenocytes were evaluated by culturing tenocytes with saline, a fiber-aligned patch, or an MSC–Exos loaded patch. In the in vivo studies, a rabbit model of chronic rotator cuff tear was established and directly repaired, repaired with fiber-aligned patch augmentation (RFPA group), and repaired with MSC–Exos loaded patch augmentation (REPA group). Histological and biomechanical analyses were performed at 4, 8, and 12 weeks after surgery. Results: An MSC–Exos loaded patch with inner aligned fibers, a loose microstructure, and reliable initial strength was fabricated using a dynamic wet-spinning system. The MSC–Exos loaded patch significantly promoted tenocyte proliferation and migration activities in vitro. In vivo, the REPA group exhibited significantly higher tendon maturing scores at 8 and 12 weeks after surgery compared with both the control and the RFPA groups. Fatty infiltration was significantly reduced in the REPA group at 4, 8, and 12 weeks compared with both the control and the RFPA groups. Biomechanical properties, including load to failure and stress, were also significantly improved at 12 weeks in the REPA group compared with both the control and the RFPA groups. Conclusion: Results in the present study suggested that an MSC–Exos loaded patch was able to enhance the repair of a chronic rotator cuff tear by providing mechanical support and minimizing degeneration. Clinical Relevance: This work supported the idea that loading bioactive MSC–Exos into a traditionally designed rotator cuff patch might exert a better effect on the repair of chronic rotator cuff tears than augmented patch repair alone.

Therapeutic Potential of Exosomes in Tendon and Tendon–Bone Healing: A Systematic Review of Preclinical Studies

“…After searching the six databases, a total of 1794 studies were found. Forty-five articles were included after screening and all of them were case–control studies [ 8 , 9 , 47 , 48 , 49 , 50 , 51 , 52 , 53 , 54 , 55 , 56 , 57 , 58 , 59 , 60 , 61 , 62 , 63 , 64 , 65 , 66 , 67 , 68 , 69 , 70 , 71 , 72 , 73 , 74 , 75 , 76 , 77 , 78 , 79 , 80 , 81 , 82 , 83 , 84 , 86 , 87 , 88 , 89 , 90 ]. Another article was included by searching the references of the included articles and review articles related to the topic [ 85 ].…”

“…All studies had a low risk of baseline characteristics under selection bias, random outcome assessment under detection bias, attrition bias, reporting bias, and other biases [ 8 , 9 , 47 , 48 , 49 , 50 , 51 , 52 , 53 , 54 , 55 , 56 , 57 , 58 , 59 , 60 , 61 , 62 , 63 , 64 , 65 , 66 , 67 , 68 , 69 , 70 , 71 , 72 , 73 , 74 , 75 , 76 , 77 , 78 , 79 , 80 , 81 , 82 , 83 , 84 , 85 , 86 , 87 , 88 , 89 , 90 ]. All studies reported baseline characteristics of the animals used which included the species, age and gender of the animals, and the outcomes were randomly assessed [ 8 , 9 , 47 , 48 , 49 , 50 , 51 , 52 ,…”

“…All studies reported baseline characteristics of the animals used which included the species, age and gender of the animals, and the outcomes were randomly assessed [ 8 , 9 , 47 , 48 , 49 , 50 , 51 , 52 , 53 , 54 , 55 , 56 , 57 , 58 , 59 , 60 , 61 , 62 , 63 , 64 , 65 , 66 , 67 , 68 , 69 , 70 , 71 , 72 , 73 , 74 , 75 , 76 , 77 , 78 , 79 , 80 , 81 , 82 , 83 , 84 , 85 , 86 , 87 , 88 , 89 , 90 ]. Therefore, all studies were assigned low risk for baseline characteristics and random outcome assessment [ 8 , 9 , 47 , 48 , 49 , 50 , 51 , 52 , 53 ,…”

“…Exosomes have been reported to play an effective therapeutic role in a variety of cancers [ 42 , 43 , 44 ], neurological diseases [ 45 ] and acute organ injuries [ 46 ]. In recent years, exosomes have also been proven to promote tendon and tendon–bone healing [ 8 , 9 , 47 , 48 , 49 , 50 , 51 , 52 , 53 , 54 , 55 , 56 , 57 , 58 , 59 , 60 , 61 , 62 , 63 , 64 , 65 , 66 , 67 , 68 , 69 , 70 , 71 , 72 , 73 , 74 , 75 , 76 , 77 , 78 , 79 , 80 , 81 , 82 , 83 , 84 , 85 , 86 , 87 , 88 , 89 , 90 ].…”

Aging‐Related Rotator Cuff Tears: Molecular Mechanisms and Implications for Clinical Management

“…The MSC‐Exos loaded patch was found to enhance the repair of chronic rotator cuff tears by providing mechanical support and mitigating muscular degeneration. [ 82 ] Similar therapeutic strategies were also developed from adipose‐derived stem cells. [ 83–85 ] A novel cell‐free treatment approach using exosomes isolated from human adipose‐derived stem cells (ASCs‐Exos) has shown promise in preventing muscle atrophy and improving biomechanical properties in a rat model of a massive rotator cuff tear.…”