Exosome biopotentiated hydrogel restores damaged skeletal muscle in a porcine model of stress urinary incontinence
Abstract Urinary incontinence afflicts up to 40% of adult women in the United States. Stress urinary incontinence (SUI) accounts for approximately one-third of these cases, precipitating ~200,000 surgical procedures annually. Continence is maintained through the interplay of sub-urethral support and...
| Main Authors: | , , , , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
Nature Portfolio
2022-09-01
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| Series: | npj Regenerative Medicine |
| Online Access: | https://doi.org/10.1038/s41536-022-00240-9 |
| _version_ | 1828167491442966528 |
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| author | Tyler J. Rolland Timothy E. Peterson Ramandeep Takhter Skylar A. Rizzo Soulmaz Boroumand Ao Shi Tyra A. Witt Mary Nagel Cassandra K. Kisby Sungjo Park Lois A. Rowe Christopher R. Paradise Laura R. E. Becher Brooke D. Paradise Paul G. Stalboerger Emanuel C. Trabuco Atta Behfar |
| author_facet | Tyler J. Rolland Timothy E. Peterson Ramandeep Takhter Skylar A. Rizzo Soulmaz Boroumand Ao Shi Tyra A. Witt Mary Nagel Cassandra K. Kisby Sungjo Park Lois A. Rowe Christopher R. Paradise Laura R. E. Becher Brooke D. Paradise Paul G. Stalboerger Emanuel C. Trabuco Atta Behfar |
| author_sort | Tyler J. Rolland |
| collection | DOAJ |
| description | Abstract Urinary incontinence afflicts up to 40% of adult women in the United States. Stress urinary incontinence (SUI) accounts for approximately one-third of these cases, precipitating ~200,000 surgical procedures annually. Continence is maintained through the interplay of sub-urethral support and urethral sphincter coaptation, particularly during activities that increase intra-abdominal pressure. Currently, surgical correction of SUI focuses on the re-establishment of sub-urethral support. However, mesh-based repairs are associated with foreign body reactions and poor localized tissue healing, which leads to mesh exposure, prompting the pursuit of technologies that restore external urethral sphincter function and limit surgical risk. The present work utilizes a human platelet-derived CD41a and CD9 expressing extracellular vesicle product (PEP) enriched for NF-κB and PD-L1 and derived to ensure the preservation of lipid bilayer for enhanced stability and compatibility with hydrogel-based sustained delivery approaches. In vitro, the application of PEP to skeletal muscle satellite cells in vitro drove proliferation and differentiation in an NF-κB-dependent fashion, with full inhibition of impact on exposure to resveratrol. PEP biopotentiation of collagen-1 and fibrin glue hydrogel achieved sustained exosome release at 37 °C, creating an ultrastructural “bead on a string” pattern on scanning electron microscopy. Initial testing in a rodent model of latissimus dorsi injury documented activation of skeletal muscle proliferation of healing. In a porcine model of stress urinary incontinence, delivery of PEP-biopotentiated collagen-1 induced functional restoration of the external urethral sphincter. The histological evaluation found that sustained PEP release was associated with new skeletal muscle formation and polarization of local macrophages towards the regenerative M2 phenotype. The results provided herein serve as the first description of PEP-based biopotentiation of hydrogels implemented to restore skeletal muscle function and may serve as a promising approach for the nonsurgical management of SUI. |
| first_indexed | 2024-04-12T02:18:26Z |
| format | Article |
| id | doaj.art-f302f092892549b692c321282915b005 |
| institution | Directory Open Access Journal |
| issn | 2057-3995 |
| language | English |
| last_indexed | 2024-04-12T02:18:26Z |
| publishDate | 2022-09-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | npj Regenerative Medicine |
| spelling | doaj.art-f302f092892549b692c321282915b0052022-12-22T03:52:12ZengNature Portfolionpj Regenerative Medicine2057-39952022-09-017111710.1038/s41536-022-00240-9Exosome biopotentiated hydrogel restores damaged skeletal muscle in a porcine model of stress urinary incontinenceTyler J. Rolland0Timothy E. Peterson1Ramandeep Takhter2Skylar A. Rizzo3Soulmaz Boroumand4Ao Shi5Tyra A. Witt6Mary Nagel7Cassandra K. Kisby8Sungjo Park9Lois A. Rowe10Christopher R. Paradise11Laura R. E. Becher12Brooke D. Paradise13Paul G. Stalboerger14Emanuel C. Trabuco15Atta Behfar16Van Cleve Cardiac Regenerative Medicine Program, Mayo Clinic Center for Regenerative MedicineVan Cleve Cardiac Regenerative Medicine Program, Mayo Clinic Center for Regenerative MedicineVan Cleve Cardiac Regenerative Medicine Program, Mayo Clinic Center for Regenerative MedicineVan Cleve Cardiac Regenerative Medicine Program, Mayo Clinic Center for Regenerative MedicineVan Cleve Cardiac Regenerative Medicine Program, Mayo Clinic Center for Regenerative MedicineVan Cleve Cardiac Regenerative Medicine Program, Mayo Clinic Center for Regenerative MedicineVan Cleve Cardiac Regenerative Medicine Program, Mayo Clinic Center for Regenerative MedicineVan Cleve Cardiac Regenerative Medicine Program, Mayo Clinic Center for Regenerative MedicineMayo Clinic Division of UrogynecologyMarriott Heart Disease Research Program, Mayo ClinicVan Cleve Cardiac Regenerative Medicine Program, Mayo Clinic Center for Regenerative MedicineRion LLCRion LLCRion LLCVan Cleve Cardiac Regenerative Medicine Program, Mayo Clinic Center for Regenerative MedicineMayo Clinic Division of UrogynecologyVan Cleve Cardiac Regenerative Medicine Program, Mayo Clinic Center for Regenerative MedicineAbstract Urinary incontinence afflicts up to 40% of adult women in the United States. Stress urinary incontinence (SUI) accounts for approximately one-third of these cases, precipitating ~200,000 surgical procedures annually. Continence is maintained through the interplay of sub-urethral support and urethral sphincter coaptation, particularly during activities that increase intra-abdominal pressure. Currently, surgical correction of SUI focuses on the re-establishment of sub-urethral support. However, mesh-based repairs are associated with foreign body reactions and poor localized tissue healing, which leads to mesh exposure, prompting the pursuit of technologies that restore external urethral sphincter function and limit surgical risk. The present work utilizes a human platelet-derived CD41a and CD9 expressing extracellular vesicle product (PEP) enriched for NF-κB and PD-L1 and derived to ensure the preservation of lipid bilayer for enhanced stability and compatibility with hydrogel-based sustained delivery approaches. In vitro, the application of PEP to skeletal muscle satellite cells in vitro drove proliferation and differentiation in an NF-κB-dependent fashion, with full inhibition of impact on exposure to resveratrol. PEP biopotentiation of collagen-1 and fibrin glue hydrogel achieved sustained exosome release at 37 °C, creating an ultrastructural “bead on a string” pattern on scanning electron microscopy. Initial testing in a rodent model of latissimus dorsi injury documented activation of skeletal muscle proliferation of healing. In a porcine model of stress urinary incontinence, delivery of PEP-biopotentiated collagen-1 induced functional restoration of the external urethral sphincter. The histological evaluation found that sustained PEP release was associated with new skeletal muscle formation and polarization of local macrophages towards the regenerative M2 phenotype. The results provided herein serve as the first description of PEP-based biopotentiation of hydrogels implemented to restore skeletal muscle function and may serve as a promising approach for the nonsurgical management of SUI.https://doi.org/10.1038/s41536-022-00240-9 |
| spellingShingle | Tyler J. Rolland Timothy E. Peterson Ramandeep Takhter Skylar A. Rizzo Soulmaz Boroumand Ao Shi Tyra A. Witt Mary Nagel Cassandra K. Kisby Sungjo Park Lois A. Rowe Christopher R. Paradise Laura R. E. Becher Brooke D. Paradise Paul G. Stalboerger Emanuel C. Trabuco Atta Behfar Exosome biopotentiated hydrogel restores damaged skeletal muscle in a porcine model of stress urinary incontinence npj Regenerative Medicine |
| title | Exosome biopotentiated hydrogel restores damaged skeletal muscle in a porcine model of stress urinary incontinence |
| title_full | Exosome biopotentiated hydrogel restores damaged skeletal muscle in a porcine model of stress urinary incontinence |
| title_fullStr | Exosome biopotentiated hydrogel restores damaged skeletal muscle in a porcine model of stress urinary incontinence |
| title_full_unstemmed | Exosome biopotentiated hydrogel restores damaged skeletal muscle in a porcine model of stress urinary incontinence |
| title_short | Exosome biopotentiated hydrogel restores damaged skeletal muscle in a porcine model of stress urinary incontinence |
| title_sort | exosome biopotentiated hydrogel restores damaged skeletal muscle in a porcine model of stress urinary incontinence |
| url | https://doi.org/10.1038/s41536-022-00240-9 |
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