Dataset Information

Treatment with Human Amniotic Suspension Allograft Improves Tendon Healing in a Rat Model of Collagenase-Induced Tendinopathy.

ABSTRACT: Treatment of tendon injuries is challenging, with neither conservative nor surgical approaches providing full recovery. Placental-derived tissues represent a promising tool for the treatment of tendon injuries. In this study, human amniotic suspension allograft (ASA) was investigated in a pre-clinical model of Achilles tendinopathy. Collagenase type I was injected in the right hind limb of Sprague Dawley rats to induce disease. Contralateral tendons were either left untreated or injected with saline as controls. Seven days following induction, tendons were injected with saline, ASA, or left untreated. Rats were sacrificed 14 and 28 days post-treatment. Histological and biomechanical analysis of tendons was completed. Fourteen days after ASA injection, improved fiber alignment and reduced cell density demonstrated improvement in degenerated tendons. Twenty-eight days post-treatment, tendons in all treatment groups showed fewer signs of degeneration, which is consistent with normal tendon healing. No statistically significant differences in histological or biomechanical analyses were observed between treatment groups at 28 days independent of the treatment they received. In this study, ASA treatment was safe, well-tolerated, and resulted in a widespread improvement of the tissue. The results of this study provide preliminary insights regarding the potential use of ASA for the treatment of Achilles tendinopathy.

SUBMITTER: de Girolamo L

PROVIDER: S-EPMC6912389 | biostudies-literature | 2019 Nov

REPOSITORIES: biostudies-literature

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Publications

Treatment with Human Amniotic Suspension Allograft Improves Tendon Healing in a Rat Model of Collagenase-Induced Tendinopathy.

de Girolamo Laura L Morlin Ambra Luiz Felipe LF Perucca Orfei Carlotta C McQuilling John P JP Kimmerling Kelly A KA Mowry Katie C KC Johnson Kimberly A KA Phan Amy T AT Whited Jessica L JL Gomoll Andreas H AH

Cells 20191108 11

Treatment of tendon injuries is challenging, with neither conservative nor surgical approaches providing full recovery. Placental-derived tissues represent a promising tool for the treatment of tendon injuries. In this study, human amniotic suspension allograft (ASA) was investigated in a pre-clinical model of Achilles tendinopathy. Collagenase type I was injected in the right hind limb of Sprague Dawley rats to induce disease. Contralateral tendons were either left untreated or injected with sa ...[more]

PMID: 31717431

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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

Treatment with Human Amniotic Suspension Allograft Improves Tendon Healing in a Rat Model of Collagenase-Induced Tendinopathy.

Publications

Treatment with Human Amniotic Suspension Allograft Improves Tendon Healing in a Rat Model of Collagenase-Induced Tendinopathy.

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