<p>Uterine fibroids (UF) are common benign tumors characterized by a higher collagen content compared to normal myometrium. Existing treatment options provide temporary relief or may impact fertility, underscoring the need for a fertility-preserving, non-invasive treatment alternative. This study aimed to explore the impact of collagenase <i>Clostridium histolyticum</i> (CCH) injection on the biomechanical properties of uterine fibroids to assess its potential as a therapeutic intervention. Between January 2018 and November 2020, 17 uterine fibroids measuring 30-50&#xa0;mm in length with adjacent myometrium of 30&#xa0;mm were obtained from patients undergoing hysterectomy for abnormal uterine bleeding. Each sample was divided into two halves, with one serving as a control and the other as an intervention. The control group samples were processed within 24&#xa0;hours of collection, while the intervention group samples were injected with&#xa0;CCH at a dose normalized to tissue volume (2 mg/cm³) and incubated for 24 hours prior to mechanical testing.&#xa0;Tissue pieces measuring 30&#xa0;mm in length, 12&#xa0;mm in width, and 2-3&#xa0;mm in thickness were prepared for mechanical testing. A tensile test was conducted using a tensile machine at a fixed speed rate of 10&#xa0;mm/min under ambient temperature conditions. The strain measured displacement, UTS indicated the stiffness of the samples. The results were presented graphically on a stress-strain curve. In fibroid tissues, UTS decreased significantly from 1.79 ± 0.07&#xa0;MPa in controls to 0.40 ± 0.04&#xa0;MPa in treated samples (Δ = −1.39, <i>P</i> &lt; 0.0001). Young’s Modulus reduced from 0.343 ± 0.068&#xa0;MPa to 0.069 ± 0.031&#xa0;MPa (Δ = −0.274, <i>P</i> = 0.00332). Conversely, myometrium tissues exhibited a modest reduction in UTS from 1.77 ± 0.04&#xa0;MPa to 1.45 ± 0.05&#xa0;MPa (Δ = −0.32, <i>P</i> &lt; 0.0001), with no significant change in&#xa0;Young’s Modulus (0.164 ± 0.129&#xa0;MPa to 0.108 ± 0.104&#xa0;MPa, Δ = −0.056, <i>P</i> = 0.94). Elongation at rupture increased in both tissues: fibroids from 4.85 ± 0.15% to 4.96 ± 0.10% (Δ = +0.11, <i>P</i> = 0.78), and myometrium from 7.12 ± 0.06% to 9.01 ± 0.05% (Δ = +1.89, <i>P</i> &lt; 0.0001). Collagenase treatment significantly weakened fibroids by reducing tensile strength and stiffness, while myometrium showed reduced strength but increased elongation due to apoptosis and reduced cell contractility. The results demonstrate that intrafibroid collagenase injections selectively soften fibroids without compromising the myometrium, highlighting its potential as a minimally invasive fibroid treatment option.</p>

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Assessing the Impact of Collagenase Clostridium histolyticum Injection on Biomechanical Properties of Uterine Fibroids and Adjacent Myometrial Tissue

  • Kobra Tahermanesh,
  • Atieh Karimzadeh,
  • Leila Allahqoli,
  • Abbas Fazel Anvari-Yazdi,
  • Negar Azarpira,
  • Roya Shahriyaripour,
  • Maryam Pourbargi,
  • Soheil Hanjani,
  • Azadeh Khorshidizadeh,
  • Ibrahim Alkatout

摘要

Uterine fibroids (UF) are common benign tumors characterized by a higher collagen content compared to normal myometrium. Existing treatment options provide temporary relief or may impact fertility, underscoring the need for a fertility-preserving, non-invasive treatment alternative. This study aimed to explore the impact of collagenase Clostridium histolyticum (CCH) injection on the biomechanical properties of uterine fibroids to assess its potential as a therapeutic intervention. Between January 2018 and November 2020, 17 uterine fibroids measuring 30-50 mm in length with adjacent myometrium of 30 mm were obtained from patients undergoing hysterectomy for abnormal uterine bleeding. Each sample was divided into two halves, with one serving as a control and the other as an intervention. The control group samples were processed within 24 hours of collection, while the intervention group samples were injected with CCH at a dose normalized to tissue volume (2 mg/cm³) and incubated for 24 hours prior to mechanical testing. Tissue pieces measuring 30 mm in length, 12 mm in width, and 2-3 mm in thickness were prepared for mechanical testing. A tensile test was conducted using a tensile machine at a fixed speed rate of 10 mm/min under ambient temperature conditions. The strain measured displacement, UTS indicated the stiffness of the samples. The results were presented graphically on a stress-strain curve. In fibroid tissues, UTS decreased significantly from 1.79 ± 0.07 MPa in controls to 0.40 ± 0.04 MPa in treated samples (Δ = −1.39, P < 0.0001). Young’s Modulus reduced from 0.343 ± 0.068 MPa to 0.069 ± 0.031 MPa (Δ = −0.274, P = 0.00332). Conversely, myometrium tissues exhibited a modest reduction in UTS from 1.77 ± 0.04 MPa to 1.45 ± 0.05 MPa (Δ = −0.32, P < 0.0001), with no significant change in Young’s Modulus (0.164 ± 0.129 MPa to 0.108 ± 0.104 MPa, Δ = −0.056, P = 0.94). Elongation at rupture increased in both tissues: fibroids from 4.85 ± 0.15% to 4.96 ± 0.10% (Δ = +0.11, P = 0.78), and myometrium from 7.12 ± 0.06% to 9.01 ± 0.05% (Δ = +1.89, P < 0.0001). Collagenase treatment significantly weakened fibroids by reducing tensile strength and stiffness, while myometrium showed reduced strength but increased elongation due to apoptosis and reduced cell contractility. The results demonstrate that intrafibroid collagenase injections selectively soften fibroids without compromising the myometrium, highlighting its potential as a minimally invasive fibroid treatment option.