Architectural and Biochemical Adaptations in Skeletal Muscle and Bone Following Rotator Cuff Injury in a Rat Model

Sato, Eugene; Killian, Megan L.; Choi, Anthony; Lin, Evie; Choo, Alexander D.; Rodríguez‐Soto, Ana E.; Lim, Chanteak; Thomopoulos, Stavros; Galatz, Leesa M.; Ward, Samuel R.

doi:10.2106/jbjs.m.01503

Cited by 16 publications

(30 citation statements)

References 33 publications

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“…Comparisons between healthy and chronically degenerative rotator cuffs have been previously made. 56,57 It has been previously shown that rodent rotator cuff muscle mass continues to increase with increasing rodent age, 60 and such growth is blunted when muscle and tendon injuries are present. 56 In the present study, we expected that the size, shape, and health of the rotator cuff complex were better for the acute injury group compared with the chronic injury group at the time of repair.…”

Section: Discussionmentioning

confidence: 99%

“…56,57 It has been previously shown that rodent rotator cuff muscle mass continues to increase with increasing rodent age, 60 and such growth is blunted when muscle and tendon injuries are present. 56 In the present study, we expected that the size, shape, and health of the rotator cuff complex were better for the acute injury group compared with the chronic injury group at the time of repair. While the overwhelming changes in the muscle and bone architecture after chronic injuries likely drive such differences, it is possible that the age of the rodent at the time of injury may also be a contributing factor to rotator cuff health.…”

Section: Discussionmentioning

confidence: 99%

“…These changes were substantially greater with the use of botulinum toxin A than with tendon detachment alone. 34,56,57 Although botulinum toxin A was used to induce atrophy in the rotator cuff muscles, it has been established that this toxin does not compromise surrounding tissues and is reversible. 23,37,47 Recent work showed that the transcriptional regulation of repair and atrophy were modulated by botulinum toxin acutely after an injection, but changes returned to baseline by 12 weeks after the injection in the rabbit tibialis anterior.…”

Section: Discussionmentioning

confidence: 99%

“…The SS and IS were surgically exposed, injected with 2.5 U of botulinum toxin A each (50 µL total volume, diluted in saline), and sharply detached from the bone at their fibrocartilaginous insertions. A botulinum toxin A injection was used to accelerate atrophy and fibrosis commonly seen in chronic tears 31,34,56,57 but did not induce a permanent injury. The contralateral limb underwent a sham operation, including exposure of both tendons and closure of the skin incision using 4-0 Vicryl (Ethicon Inc).…”

Section: Methodsmentioning

confidence: 99%

“…32 Likewise, chronic detachment of both the SS and infraspinatus (IS) tendons can lead to substantial muscle and bone changes in a rodent model of rotator cuff disease, and these changes are magnified in the presence of short-term muscle paralysis. 56,57 A delay in repair after a single-tendon (ie, SS) injury of 3 weeks has been associated with a marked decrease in bone density, decreased material properties, and impaired organization. 12 A delay in rotator cuff repair after a single-tendon (ie, SS) injury led to increased repair site tension, which was strongly correlated with repair site stiffness, strength, and increased cross-sectional area.…”

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Chronic Degeneration Leads to Poor Healing of Repaired Massive Rotator Cuff Tears in Rats

et al. 2015

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Background Chronic rotator cuff tears present a clinical challenge, often with poor outcomes after surgical repair. Degenerative changes to the muscle, tendon, and bone are thought to hinder healing after surgical repair; additionally, the ability to overcome degenerative changes after surgical repair remains unclear. Purpose/Hypothesis The purpose of this study was to evaluate healing outcomes of muscle, tendon, and bone after tendon repair in a model of chronic rotator cuff disease and to compare these outcomes to those of acute rotator cuff injuries and repair. The hypothesis was that degenerative rotator cuff changes associated with chronic multitendon tears and muscle unloading would lead to poor structural and mechanical outcomes after repair compared with acute injuries and repair. Study Design Controlled laboratory study. Methods Chronic rotator cuff injuries, induced via detachment of the supraspinatus (SS) and infraspinatus (IS) tendons and injection of botulinum toxin A into the SS and IS muscle bellies, were created in the shoulders of rats. After 8 weeks of injury, tendons were surgically reattached to the humeral head, and an acute, dual-tendon injury and repair was performed on the contralateral side. After 8 weeks of healing, muscles were examined histologically, and tendon-to-bone samples were examined microscopically, histologically, and biomechanically and via micro–computed tomography. Results All repairs were intact at the time of dissection, with no evidence of gapping or ruptures. Tendon-to-bone healing after repair in our chronic injury model led to reduced bone quality and morphological disorganization at the repair site compared with acute injuries and repair. SS and IS muscles were atrophic at 8 weeks after repair of chronic injuries, indicating incomplete recovery after repair, whereas SS and IS muscles exhibited less atrophy and degeneration in the acute injury group at 8 weeks after repair. After chronic injuries and repair, humeral heads had decreased total mineral density and an altered trabecular structure, and the repair had decreased strength, stiffness, and toughness, compared with the acute injury and repair group. Conclusion Chronic degenerative changes in rotator cuff muscles, tendons, and bone led to inferior healing characteristics after repair compared with acute injuries and repair. The changes were not reversible after repair in the time course studied, consistent with clinical impressions. Clinical Relevance High retear rates after rotator cuff repair are associated with tear size and chronicity. Understanding the mechanisms behind this association may allow for targeted tissue therapy for tissue degeneration that occurs in the setting of chronic tears.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

mentioning

confidence: 99%

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Chronic Degeneration Leads to Poor Healing of Repaired Massive Rotator Cuff Tears in Rats

et al. 2015

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Biologically‐coupled bisphosphonate chaperones effectively deliver molecules to the site of soft tissue‐bone healing

Kremen

Shi

et al. 2023

Journal Orthopaedic Research

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Tendon injuries are common and often treated surgically, however, current tendon repair healing results in poorly organized fibrotic tissue. While certain growth factors have been reported to improve both the strength and organization of the repaired enthesis, their clinical applicability is severely limited due to a lack of appropriate delivery strategies. In this study, we evaluated a recently developed fluorescent probe, Osteoadsorptive Fluorogenic Sentinel‐3 that is composed of a bone‐targeting bisphosphonate (BP) moiety linked to fluorochrome and quencher molecules joined via a cathepsin K‐sensitive peptide sequence. Using a murine Achilles tendon‐to‐bone repair model, BP‐based and/or Ctsk‐coupled imaging probes were applied either locally or systemically. Fluorescence imaging was used to quantify the resultant signal in vivo. After tendon‐bone repair, animals that received either local or systemic administration of imaging probes demonstrated significantly higher fluorescence signal at the repair site compared to the sham surgery group at all time points (p < 0.001), with signal peaking at 7–10 days after surgery. Our findings demonstrate the feasibility of using a novel BP‐based targeting and Ctsk‐activated delivery of molecules to the site of tendon‐to‐bone repair and creates a foundation for further development of this platform as an effective strategy to deliver bioactive molecules to sites of musculoskeletal injury.

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Arthroscopic reduction internal fixation for glenoid fractures: a systematic review of the outcomes and complications

Mousa,

Aresti

2024

Musculoskelet Surg

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Architectural and Biochemical Adaptations in Skeletal Muscle and Bone Following Rotator Cuff Injury in a Rat Model

Abstract: Structural musculoskeletal changes occur after tendon injury, and these changes are severely exacerbated with the addition of neuromuscular compromise.

Cited by 16 publications

References 33 publications

Chronic Degeneration Leads to Poor Healing of Repaired Massive Rotator Cuff Tears in Rats

Chronic Degeneration Leads to Poor Healing of Repaired Massive Rotator Cuff Tears in Rats

Biologically‐coupled bisphosphonate chaperones effectively deliver molecules to the site of soft tissue‐bone healing

Arthroscopic reduction internal fixation for glenoid fractures: a systematic review of the outcomes and complications

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