Focused Ultrasound Mechanical Disruption of <i>Ex Vivo</i> Rat Tendon

Smallcomb, Molly; Elliott, Jacob C.; Khandare, Sujata; Butt, Ali A.; Vidt, Meghan E.; Simon, Julianna C.

doi:10.1109/tuffc.2021.3075375

Cited by 10 publications

(9 citation statements)

References 26 publications

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“…For fUS, a spherically curved single‐element fUS transducer of 1.5 MHz operating frequency and f‐number of 0.7 (H‐234 modified with 42‐mm central opening; Sonic Concepts) and linear radiofrequency power amplifier (55 dB, 1040 L; Electronics & Innovations Ltd.) were used to deliver 1 ms pulses at 10 Hz for 106 s with peak positive and negative pressures of 49 and 19 MPa, respectively, while the rat was partially submerged in a degassed, deionized water tank (Figure 1). These parameters were based on our previous ex vivo parameter exploration studies 19,20 . Focal dimensions, or full widths at half maximum pressures, were measured with a fiber optic probe hydrophone (HFO‐690; ONDA) to be 10.5 mm axially and 1 mm transversely for a peak negative pressure of 19 MPa (Figure 1).…”

Section: Methodsmentioning

confidence: 99%

“…16 Focused ultrasound (fUS) is a promising, noninvasive, clinically adopted treatment modality that focuses acoustic energy within a well-defined focal volume to create thermal and/or mechanical bioeffects without damaging the intervening tissue. 17,18 Our previous ex vivo studies [19][20][21][22] explored a range of fUS parameters on ex vivo murine tendons and compared the histological and mechanical effects to DN. Smallcomb et al 20 found that mild mechanical disruption, or nonthermal microdamage in the form of localized fiber separation and/or fiber pattern disruption, was achievable histologically in ex vivo tendons for a small window of fUS acoustic parameters.…”

Section: Introductionmentioning

confidence: 99%

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Focused ultrasound as an alternative to dry needling for the treatment of tendinopathies: A murine model

Khandare,

Smallcomb,

Elliott

et al. 2023

Journal Orthopaedic Research

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Tendinopathies account for 30% of 102 million annual musculoskeletal injuries occurring annually in the United States. Current treatments, like dry needling, induce microdamage to promote healing but produce mixed success rates. Previously, we showed focused ultrasound can noninvasively create microdamage while preserving mechanical properties in ex vivo murine tendons. This present study compared growth factor, histological, and mechanical effects after focused ultrasound or dry needling treatments in an in vivo murine tendon injury model. Partial Achilles tenotomy was performed in 26 rats. One‐week postsurgery, tendons were treated with focused ultrasound (1.5 MHz, 1‐ms pulses at 10 Hz for 106 s, p+ = 49 MPa, p− = 19 MPa) or dry needling (30 G needle, 5 fenestrations over 20 s) and survived for 1 additional week. Blood was collected immediately before and after treatment and before euthanasia; plasma was assayed for growth factors. Treated tendons and contralateral controls were harvested for histology or mechanical testing. No differences were found between treatments in release of insulin growth factor 1 and transforming growth factor beta; vascular endothelial growth factor A concentrations were too low for detection. Histologically, focused ultrasound and dry needling tendons displayed localized fibroblast infiltration without collagen proliferation with no detectable differences between treatments. Mechanically, stiffness and percent relaxation of dry needling tendons were lower than controls (p = 0.0041, p = 0.0441, respectively), whereas stiffness and percent relaxation of focused ultrasound tendons were not different from controls. These results suggest focused ultrasound should be studied further to determine how this modality can be leveraged as a therapy for tendinopathies.

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Section: Methodsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Focused ultrasound as an alternative to dry needling for the treatment of tendinopathies: A murine model

Khandare,

Smallcomb,

Elliott

et al. 2023

Journal Orthopaedic Research

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“…The ultrasonic energy was focused to a depth of 45 mm by the geometrically curved body of the transducer. Full width at half-maximum beam profiles of the focused ultrasound transducer were measured at a peak positive pressure of 37 MPa to be 0.6 mm transversely and 5 mm axially . The transducer was driven at an operational frequency of 1.5 MHz by using a 33600A Series waveform generator (Keysight, Santa Rosa, CA) and a 55 dB A500 linear radiofrequency power amplifier (Electronic Navigation Industries, Rochester, NY) .…”

Section: Materials and Methodsmentioning

confidence: 99%

“…Full width at half-maximum beam profiles of the focused ultrasound transducer were measured at a peak positive pressure of 37 MPa to be 0.6 mm transversely and 5 mm axially. 36 The transducer was driven at an operational frequency of 1.5 MHz by using a 33600A Series waveform generator (Keysight, Santa Rosa, CA) and a 55 dB A500 linear radiofrequency power amplifier (Electronic Navigation Industries, Rochester, NY). 36 Gels were targeted at the focus with repeated pulses (20 ms, 1 Hz) with increasing peak positive pressures of 37, 57, and 75 MPa (peak negative pressures of 16, 29, and 32 MPa, respectively).…”

Section: ■ Introductionmentioning

confidence: 99%

“…36 The transducer was driven at an operational frequency of 1.5 MHz by using a 33600A Series waveform generator (Keysight, Santa Rosa, CA) and a 55 dB A500 linear radiofrequency power amplifier (Electronic Navigation Industries, Rochester, NY). 36 Gels were targeted at the focus with repeated pulses (20 ms, 1 Hz) with increasing peak positive pressures of 37, 57, and 75 MPa (peak negative pressures of 16, 29, and 32 MPa, respectively). A HFO-690 fiber optic probe hydrophone (ONDA, Sunnyvale, CA) was used to measure focal pressures in the lowest-pressure case.…”

Section: ■ Introductionmentioning

confidence: 99%

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Ultrasound-Responsive Hydrogels for On-Demand Protein Release

Arrizabalaga

Smallcomb

Abu‐Laban

et al. 2022

ACS Appl. Bio Mater.

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The development of tunable, ultrasound-responsive hydrogels that can deliver protein payload on-demand when exposed to focused ultrasound is described in this study. Reversible Diels−Alder linkers, which undergo a retro reaction when stimulated with ultrasound, were used to cross-link chitosan hydrogels with entrapped FITC-BSA as a model protein therapeutic payload. Two Diels−Alder linkage compositions with large differences in the reverse reaction energy barriers were compared to explore the influence of linker composition on ultrasound response. Selected physicochemical properties of the hydrogel construct, its basic degradation kinetics, and its cytocompatibility were measured with respect to Diels−Alder linkage composition. Focused ultrasound initiated the retro Diels− Alder reaction, controlling the release of the entrapped payload while also allowing for real-time visualization of the ongoing process. Additionally, increasing the focused ultrasound amplitude and time correlated with an increased rate of protein release, indicating stimuli responsive control.

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