RESUMO
Background: Radiation-induced fibrosis (RIF) is a debilitating sequelae of radiation therapy that has been shown to improve with topical treatment with the iron chelator deferoxamine (DFO). We investigated whether DFO exerts this effect through attenuation of ferroptosis, a recently described iron-dependent pathway of cell death. Methods: Adult C57BL/6J mice were treated with topical DFO or ferrostastin-1 (Fer-1) and irradiated with 30 Grays of ionizing radiation to the dorsal skin to promote development of chronic RIF. Immunofluorescent staining with 4-hydroxynonenal (4-HNE) antibody was carried out directly following irradiation to assess ferroptosis activity. Perfusion testing with laser Doppler was performed throughout the healing interval. Eight weeks following radiation, dorsal skin was harvested and analyzed histologically and biomechanically. Results: Immunohistochemical staining demonstrated lower presence of 4-HNE in non-irradiated skin, DFO-treated skin, and Fer-1-treated skin compared to irradiated, untreated skin. DFO resulted in histological measurements (dermal thickness and collagen content) that resembled normal skin, while Fer-1 treatment yielded less significant improvements. These results were mirrored by analysis of extracellular matrix ultrastructure and biomechanical testing, which recapitulated the ability of topical DFO treatment to alleviate RIF across these parameters while Fer-1 resulted in less notable improvement. Finally, perfusion levels in DFO treated irradiated skin were similar to measurements in normal skin, while Fer-1 treatment did not impact this feature. Conclusions: Ferroptosis contributes to the development of RIF and attenuation of this process leads to reduced skin injury. DFO further improves RIF through additional enhancement of perfusion not seen with Fer-1.
RESUMO
PURPOSE: Although tendon lacerations are common, there is currently no consensus on choice of suture. Easy and fast sutures that impart enough strength to allow mobilization are needed. This study compared the ex vivo biomechanical strength (force required to create a 2 mm tendon gap) of a novel suture (ST-knot) with that of a conventional suture (double Kessler). MATERIALS AND METHODS: Forty fresh deep flexor tendons from porcine forelimbs were used. Both repaired tendon ends were mounted on standard traction jaws of an axial traction machine at an initial distance of 40 mm for all tendons. A high-definition camera was used to determine the force forming a 2 mm gap. Ten tendons in group 1 (ST-knot) and 10 in group 2 (double Kessler) were prepared with PDS 4.0 (single thread for Kessler, double thread for ST-knot). Tendons in groups 3 (ST-knot) and 4 (double Kessler) were repaired with PDS 1.0 using the same principle. RESULTS: There was no significant difference in the force required to form a 2 mm tendon gap between groups 1 and 2, and this trend was identical when using a stronger thread in groups 3 and 4. The maximum force before rupture, mode of repair failure, stress and stiffness were also comparable, with no significant differences between groups 1 and 2, or between groups 3 and 4. CONCLUSIONS: The ST-knot showed comparable results to the double-Kessler knot, whichever the thread used. Because it involves fewer steps than conventional techniques and is easy to perform, the ST-knot may offer a therapeutic solution, particularly in complex trauma with multiple tendon injury.