Dataset Information

The effects of chronic unloading and gap formation on tendon-to-bone healing in a rat model of massive rotator cuff tears.

ABSTRACT: The objective of this study was to understand the effect of pre-repair rotator cuff chronicity on post-repair healing outcomes using a chronic and acute multi-tendon rat rotator cuff injury model. Full-thickness dual tendon injuries (supra- and infraspinatus) were created unilaterally in adult male Sprague Dawley rats, and left chronically detached for 8 or 16 weeks. After chronic detachment, tears were repaired and acute dual tendon injuries were created and immediately repaired on contralateral shoulders. Tissue level outcomes for bone, tendon, and muscle were assessed 4 or 8 weeks after repair using histology, microcomputed tomography, biomechanical testing, and biochemical assays. Substantial gap formation was seen in 35% of acute repairs and 44% of chronic repairs. Gap formation negatively correlated with mechanical and structural outcomes for both healing time points regardless of injury duration. Bone and histomorphometry, as well as biomechanics, were similar between acute and chronic injury and repair regardless of chronicity and duration of healing. This study was the first to implement a multi-tendon rotator cuff injury with surgical repair following both chronic and acute injuries. Massive tear in a rodent model resulted in gap formation regardless of injury duration which had detrimental effects on repair outcomes.

SUBMITTER: Killian ML

PROVIDER: S-EPMC3900302 | biostudies-literature | 2014 Mar

REPOSITORIES: biostudies-literature

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The effects of chronic unloading and gap formation on tendon-to-bone healing in a rat model of massive rotator cuff tears.

Killian Megan L ML Cavinatto Leonardo L Shah Shivam A SA Sato Eugene J EJ Ward Samuel R SR Havlioglu Necat N Galatz Leesa M LM Thomopoulos Stavros S

Journal of orthopaedic research : official publication of the Orthopaedic Research Society 20131114 3

The objective of this study was to understand the effect of pre-repair rotator cuff chronicity on post-repair healing outcomes using a chronic and acute multi-tendon rat rotator cuff injury model. Full-thickness dual tendon injuries (supra- and infraspinatus) were created unilaterally in adult male Sprague Dawley rats, and left chronically detached for 8 or 16 weeks. After chronic detachment, tears were repaired and acute dual tendon injuries were created and immediately repaired on contralatera ...[more]

PMID: 24243733

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Project description:BackgroundMore than 450,000 rotator cuff repairs are performed annually, yet healing of tendon to bone often fails. This failure is rooted in the fibrovascular healing response, which does not regenerate the native attachment site. Better healing outcomes may be achieved by targeting inflammation during the early period after repair. Rather than broad inhibition of inflammation, which may impair healing, the current study utilized a molecularly targeted approach to suppress IKKβ, shutting down only the inflammatory arm of the nuclear factor κB (NF-κB) signaling pathway.PurposeTo evaluate the therapeutic potential of IKKβ inhibition in a clinically relevant model of rat rotator cuff repair.Study designControlled laboratory study.MethodsAfter validating the efficacy of the IKKβ inhibitor in vitro, it was administered orally once a day for 7 days after surgery in a rat rotator cuff repair model. The effect of treatment on reducing inflammation and improving repair quality was evaluated after 3 days and 2, 4, and 8 weeks of healing, using gene expression, biomechanics, bone morphometry, and histology.ResultsInhibition of IKKβ attenuated cytokine and chemokine production in vitro, demonstrating the potential for this inhibitor to reduce inflammation in vivo. Oral treatment with IKKβ inhibitor reduced NF-κB target gene expression by up to 80% compared with a nontreated group at day 3, with a subset of these genes suppressed through 14 days. Furthermore, the IKKβ inhibitor led to enhanced tenogenesis and extracellular matrix production, as demonstrated by gene expression and histological analyses. At 4 weeks, inhibitor treatment led to increased toughness, no effects on failure load and strength, and decreases in stiffness and modulus when compared with vehicle control. At 8 weeks, IKKβ inhibitor treatment led to increased toughness, failure load, and strength compared with control animals. IKKβ inhibitor treatment prevented the bone loss near the tendon attachment that occurred in repairs in control.ConclusionPharmacological inhibition of IKKβ successfully suppressed excessive inflammation and enhanced tendon-to-bone healing after rotator cuff repair in a rat model.Clinical relevanceThe NF-κB pathway is a promising target for enhancing outcomes after rotator cuff repair.

Dataset Information

The effects of chronic unloading and gap formation on tendon-to-bone healing in a rat model of massive rotator cuff tears.

Publications

The effects of chronic unloading and gap formation on tendon-to-bone healing in a rat model of massive rotator cuff tears.

Similar Datasets

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