Biomechanical Testing of Murine Tendons

Kurtaliaj, Iden; Golman, Mikhail; Abraham, Adam C.; Thomopoulos, Stavros

doi:10.3791/60280

Cited by 24 publications

(32 citation statements)

References 39 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…After microCT scanning, the supraspinatus muscle was carefully removed from the tendon and the humerus was placed into custom 3-dimensional (3-D) printed fixtures 27 and tested in a saline bath at 37°C (Electroforce 3230; TA Instruments). For repair samples, the suture was cut before testing.…”

Section: Methodsmentioning

confidence: 99%

Enhanced Tendon-to-Bone Healing via IKKβ Inhibition in a Rat Rotator Cuff Model

Golman

Skouteris

et al. 2021

Am J Sports Med

Self Cite

View full text Add to dashboard Cite

Background: More 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. Purpose: To evaluate the therapeutic potential of IKKβ inhibition in a clinically relevant model of rat rotator cuff repair. Study Design: Controlled laboratory study. Methods: After 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. Results: Inhibition 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. Conclusion: Pharmacological inhibition of IKKβ successfully suppressed excessive inflammation and enhanced tendon-to-bone healing after rotator cuff repair in a rat model. Clinical Relevance: The NF-κB pathway is a promising target for enhancing outcomes after rotator cuff repair.

show abstract

Section: Methodsmentioning

confidence: 99%

Enhanced Tendon-to-Bone Healing via IKKβ Inhibition in a Rat Rotator Cuff Model

Golman

Skouteris

et al. 2021

Am J Sports Med

Self Cite

View full text Add to dashboard Cite

show abstract

“…For biomechanical testing, Achilles tendons were dissected at D56, wrapped in PBS-soaked gauze and frozen at −20C until time of testing. Tensile testing was performed in PBS at room temperature using custom 3D printed grips to secure the calcaneus bone and Achilles tendon (27, 28). Tendons were preloaded to 0.05N for ~1 min followed by ramp to failure at 1%/s.…”

Section: Methodsmentioning

confidence: 99%

Macrophage depletion impairs neonatal tendon regeneration

Howell

Kaji

Montero

et al. 2021

Preprint

View full text Add to dashboard Cite

Tendons are dense connective tissues that transmit muscle forces to the skeleton. After adult injury, healing potential is generally poor and dominated by scar formation. Although the immune response is a key feature of healing, the specific immune cells and signals that drive tendon healing have not been fully defined. In particular, the immune regulators underlying tendon regeneration are almost completely undetermined due to a paucity of tendon regeneration models. Using a mouse model of neonatal tendon regeneration, we screened for immune-related markers and identified upregulation of several genes associated with inflammation, macrophage chemotaxis, and TGFβ signaling after injury. Depletion of macrophages using AP20187 treatment of MaFIA mice resulted in impaired functional healing, reduced cell proliferation, reduced ScxGFP+ neo-tendon formation, and altered tendon gene expression. Collectively, these results show that inflammation is a key component of neonatal tendon regeneration and demonstrate a requirement for macrophages in effective functional healing.

show abstract

“…In vitro limitations include considerable issues associated with the gripping of the two tendon ends, which precludes the testing of the tendon-to-bone attachment. Testing the strength of the tendon-to-bone attachment is of considerable clinical value as rotator cuff re-tears usually develop at the junction between the tendon and the bone [131,132]. Although there are limitations with the biomechanical models used, the data reviewed is useful and all included studies faced the same limitations, making results comparable, with a trend towards improved maximum force, elastic modulus, and strength in EV treated groups.…”

Section: In Vivo Findingsmentioning

confidence: 99%

“…Recommendations for future work would be the ex vivo testing of biomechanics using novel 3D-printed fixtures that exactly match the anatomies of the humerus and calcaneus to mechanically test supraspinatus tendon and Achilles tendon, respectively. Kurtaliaj et al's new approach eliminated artifactual gripping failures (e.g., growth plate failure rather than in the tendon), decreased overall testing time, and increased reproducibility [132]. Furthermore, it is challenging to generate models which mimic the cumulative damage seen in age or overuse related tendinopathy.…”

Section: In Vivo Findingsmentioning

confidence: 99%

Mesenchymal Stem Cell-Derived Extracellular Vesicles in Tendon and Ligament Repair—A Systematic Review of In Vivo Studies

Tennyson

Zhang

et al. 2021

Cells

View full text Add to dashboard Cite

Tendon and ligament injury poses an increasingly large burden to society. This systematic review explores whether mesenchymal stem cell-derived extracellular vesicles (MSC-EVs) can facilitate tendon/ligament repair in vivo. On 26 May 2021, a systematic search was performed on PubMed, Web of Science, Cochrane Library, Embase, to identify all studies that utilised MSC-EVs for tendon/ligament healing. Studies administering EVs isolated from human or animal-derived MSCs into in vivo models of tendon/ligament injury were included. In vitro, ex vivo, and in silico studies were excluded, and studies without a control group were excluded. Out of 383 studies identified, 11 met the inclusion criteria. Data on isolation, the characterisation of MSCs and EVs, and the in vivo findings in in vivo models were extracted. All included studies reported better tendon/ligament repair following MSC-EV treatment, but not all found improvements in every parameter measured. Biomechanics, an important index for tendon/ligament repair, was reported by only eight studies, from which evidence linking biomechanical alterations to functional improvement was weak. Nevertheless, the studies in this review showcased the safety and efficacy of MSC-EV therapy for tendon/ligament healing, by attenuating the initial inflammatory response and accelerating tendon matrix regeneration, providing a basis for potential clinical use in tendon/ligament repair.

show abstract

Biomechanical Testing of Murine Tendons

Cited by 24 publications

References 39 publications

Enhanced Tendon-to-Bone Healing via IKKβ Inhibition in a Rat Rotator Cuff Model

Enhanced Tendon-to-Bone Healing via IKKβ Inhibition in a Rat Rotator Cuff Model

Macrophage depletion impairs neonatal tendon regeneration

Mesenchymal Stem Cell-Derived Extracellular Vesicles in Tendon and Ligament Repair—A Systematic Review of In Vivo Studies

Contact Info

Product

Resources

About