A dual-phase biologic augmentation of rotator cuff healing in a preclinical rat model using interleukin-17F and low-dose lithium

Background: Rotator cuff tendon tears are a common cause of shoulder dysfunction in adults. Yet, impaired healing continues to result in higher failure rates after surgical repair resulting in patient dysfunction and prolonged recovery. This has spurred increased investigation of biologic augmentati...

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Main Authors: Manisha R. Mistry, MD, MSc, Yufa Wang, MD, MSc, Cari M. Whyne, PhD, David M. Phillips, MSc, Wendy Oakden, PhD, Paul Marks, MD, Jimmy Tat, MD, MSc, Diane Nam, MD, MSc
Format: Article
Language:English
Published: Elsevier 2025-01-01
Series:JSES International
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Online Access:http://www.sciencedirect.com/science/article/pii/S2666638324004742
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author Manisha R. Mistry, MD, MSc
Yufa Wang, MD, MSc
Cari M. Whyne, PhD
David M. Phillips, MSc
Wendy Oakden, PhD
Paul Marks, MD
Jimmy Tat, MD, MSc
Diane Nam, MD, MSc
author_facet Manisha R. Mistry, MD, MSc
Yufa Wang, MD, MSc
Cari M. Whyne, PhD
David M. Phillips, MSc
Wendy Oakden, PhD
Paul Marks, MD
Jimmy Tat, MD, MSc
Diane Nam, MD, MSc
author_sort Manisha R. Mistry, MD, MSc
collection DOAJ
description Background: Rotator cuff tendon tears are a common cause of shoulder dysfunction in adults. Yet, impaired healing continues to result in higher failure rates after surgical repair resulting in patient dysfunction and prolonged recovery. This has spurred increased investigation of biologic augmentation to improve tendon healing. This study examines the outcome of peritendinous interleukin-17F (IL-17F) administration and oral low-dose lithium carbonate (Li) on rotator cuff healing following acute surgical repair in a rat model. Methods: Treatment group included an open supraspinatus peel and repair followed by a local injection of IL-17F at the bone–tendon interface and a 7-day course of oral Li. Control rats received no additional intervention before surgical closure. Evaluation of healing was then preformed using MRI imaging, biomechanical testing, and histological analysis at the bone–tendon interface. Results: Eighteen rats (9 control, 9 experimental) underwent complete testing. Combined treatment of peritendinous IL-17F and oral low-dose Li after rotator cuff repair improved rotator cuff healing in all outcomes when compared to controls. MRI imaging in the treatment group showed complete healing of all supraspinatus tendons across the anatomic footprint after repair. We also found significant increases in biomechanical stiffness compared to controls (P < .01). At the histological level, treatment groups also had decreased osteoclasts (P < .001), and increased histologic organization of fibroblasts compared to controls. These findings are consistent with an increase in biomechanical stiffness. Conclusion: We demonstrated that the combined treatment of IL-17F and oral low-dose lithium improved rotator cuff tendon healing quality following acute surgical repair in a rat model.
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spelling doaj-art-3ecf17ad549a4073869e234bb15d7c8e2025-01-12T05:26:06ZengElsevierJSES International2666-63832025-01-0191306312A dual-phase biologic augmentation of rotator cuff healing in a preclinical rat model using interleukin-17F and low-dose lithiumManisha R. Mistry, MD, MSc0Yufa Wang, MD, MSc1Cari M. Whyne, PhD2David M. Phillips, MSc3Wendy Oakden, PhD4Paul Marks, MD5Jimmy Tat, MD, MSc6Diane Nam, MD, MSc7Division of Orthopaedic Surgery, Department of Surgery, The University of Ottawa, Ottawa, Ontario, Canada; Division of Orthopaedic Surgery, Department of Surgery, The University of Toronto, Toronto, Ontario, CanadaSunnybrook Research Institute, Sunnybrook Health Sciences Centre, Toronto, Ontario, CanadaDivision of Orthopaedic Surgery, Department of Surgery, The University of Toronto, Toronto, Ontario, Canada; Sunnybrook Research Institute, Sunnybrook Health Sciences Centre, Toronto, Ontario, Canada; Biomedical Engineering, University of Toronto, Toronto, Ontario, CanadaBiomedical Engineering, University of Toronto, Toronto, Ontario, CanadaSunnybrook Research Institute, Sunnybrook Health Sciences Centre, Toronto, Ontario, CanadaDivision of Orthopaedic Surgery, Department of Surgery, The University of Toronto, Toronto, Ontario, CanadaDivision of Orthopaedic Surgery, Department of Surgery, The University of Toronto, Toronto, Ontario, CanadaDivision of Orthopaedic Surgery, Department of Surgery, The University of Toronto, Toronto, Ontario, Canada; Sunnybrook Research Institute, Sunnybrook Health Sciences Centre, Toronto, Ontario, Canada; Corresponding author: Diane Nam, MD, MSc, Sunnybrook Health Sciences Centre, MG301-2075 Bayview Ave, Toronto, Ontario M4N 3M5, Canada.Background: Rotator cuff tendon tears are a common cause of shoulder dysfunction in adults. Yet, impaired healing continues to result in higher failure rates after surgical repair resulting in patient dysfunction and prolonged recovery. This has spurred increased investigation of biologic augmentation to improve tendon healing. This study examines the outcome of peritendinous interleukin-17F (IL-17F) administration and oral low-dose lithium carbonate (Li) on rotator cuff healing following acute surgical repair in a rat model. Methods: Treatment group included an open supraspinatus peel and repair followed by a local injection of IL-17F at the bone–tendon interface and a 7-day course of oral Li. Control rats received no additional intervention before surgical closure. Evaluation of healing was then preformed using MRI imaging, biomechanical testing, and histological analysis at the bone–tendon interface. Results: Eighteen rats (9 control, 9 experimental) underwent complete testing. Combined treatment of peritendinous IL-17F and oral low-dose Li after rotator cuff repair improved rotator cuff healing in all outcomes when compared to controls. MRI imaging in the treatment group showed complete healing of all supraspinatus tendons across the anatomic footprint after repair. We also found significant increases in biomechanical stiffness compared to controls (P < .01). At the histological level, treatment groups also had decreased osteoclasts (P < .001), and increased histologic organization of fibroblasts compared to controls. These findings are consistent with an increase in biomechanical stiffness. Conclusion: We demonstrated that the combined treatment of IL-17F and oral low-dose lithium improved rotator cuff tendon healing quality following acute surgical repair in a rat model.http://www.sciencedirect.com/science/article/pii/S2666638324004742Rotator cuff healingCytokinesIL-17FLithium carbonateRat modelRotator cuff repair
spellingShingle Manisha R. Mistry, MD, MSc
Yufa Wang, MD, MSc
Cari M. Whyne, PhD
David M. Phillips, MSc
Wendy Oakden, PhD
Paul Marks, MD
Jimmy Tat, MD, MSc
Diane Nam, MD, MSc
A dual-phase biologic augmentation of rotator cuff healing in a preclinical rat model using interleukin-17F and low-dose lithium
JSES International
Rotator cuff healing
Cytokines
IL-17F
Lithium carbonate
Rat model
Rotator cuff repair
title A dual-phase biologic augmentation of rotator cuff healing in a preclinical rat model using interleukin-17F and low-dose lithium
title_full A dual-phase biologic augmentation of rotator cuff healing in a preclinical rat model using interleukin-17F and low-dose lithium
title_fullStr A dual-phase biologic augmentation of rotator cuff healing in a preclinical rat model using interleukin-17F and low-dose lithium
title_full_unstemmed A dual-phase biologic augmentation of rotator cuff healing in a preclinical rat model using interleukin-17F and low-dose lithium
title_short A dual-phase biologic augmentation of rotator cuff healing in a preclinical rat model using interleukin-17F and low-dose lithium
title_sort dual phase biologic augmentation of rotator cuff healing in a preclinical rat model using interleukin 17f and low dose lithium
topic Rotator cuff healing
Cytokines
IL-17F
Lithium carbonate
Rat model
Rotator cuff repair
url http://www.sciencedirect.com/science/article/pii/S2666638324004742
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