We showed previously that microbubble destruction with pulsed 1-MHz ultrasound creates a bioeffect that stimulates arteriogenesis and a chronic increase in hyperemia blood flow in normal rat muscle. Here we tested whether ultrasonic microbubble destruction can be used to create a microvascular remodeling response that restores hyperemia blood flow to rat skeletal muscle affected by arterial occlusion. Pulsed ultrasound (1 MHz) was applied to gracilis muscles in which the lateral feed artery was occluded but the medial feed artery was left intact. Control muscles were similarly occluded but did not receive ultrasound, microbubbles, or both. Hyperemia blood flow and number of smooth muscle (SM) alpha-actin-positive vessels, >30-mum arterioles, and capillaries per fiber were determined 7, 14, and 28 days after treatment. In ultrasound-microbubble-treated muscles, lateral region hyperemia blood flow was increased at all time points and restored to normal at day 28. The number of SM alpha-actin vessels per fiber was increased over control in this region at days 7 and 14 but decreased by day 28, when larger-diameter arterioles became more prevalent in the medial region. The number of capillaries per fiber was increased over control only at day 7 in the lateral region and only at days 7 and 14 in the medial region, indicating that the angiogenesis response was transient and likely did not contribute significantly to flow restoration at day 28. We conclude that ultrasonic microbubble destruction can be tailored to stimulate an arteriogenesis response that restores hyperemia blood flow to skeletal muscle in a rat model of arterial occlusion.
To determine the degree to which intramuscular pressure (IMP) and muscle force are correlated in an intact compartment, a custom pressure transducer was inserted into the rabbit tibialis anterior (TA) while activating the muscle via the peroneal nerve and measuring TA muscle force distal to the ankle retinaculum. In general, IMP was more variable compared to muscle force throughout the entire isometric length-tension relationship. In contrast to results obtained on isolated TA muscles, IMP-force relations with the compartment intact were not significantly different between the ascending and descending limbs of the length-tension curve. Specifically, average relative pressure-force coefficients of determination (r2) were 0.76±0.11 for the active ascending limb and 0.98±0.01 for the active descending limb. These data demonstrate that muscle force and IMP are fairly well correlated under isometric conditions and that this relationship is not improved by measuring IMP in an intact environment.
Objectives/Hypothesis The purpose of this study was to develop and provide evidence of a novel permanent injectable biomaterial for vocal fold augmentation with the potential to treat glottic incompetence by evaluating its performance in two animal models. Study Design Animal model. Methods Microporous annealed particle (MAP) hydrogel was fabricated using a water‐in‐oil emulsion method and synthetically tuned to match the stiffness modulus of native vocalis muscle. Thirty‐two New Zealand White rabbits were administered unilateral injections of MAP (n = 16), saline (n = 8), and the clinical standard hyaluronic acid (Restylane‐L) (n = 8), and evaluated at day 0, and 6‐week, 4‐month, and 6‐month endpoints. Induced vocal fold vibration was recorded with a high‐speed camera prior to euthanization, with glottic closure and mucosal wave characteristics assessed both quantitatively and qualitatively by an experienced voice clinician. Histologic analysis was performed to assess scaffold permanence, immunogenicity, and vascularization within the scaffold. Results Histologic analysis confirmed the MAP gel treatment group maintained its volume without migration for 6 months postimplantation. Immune staining showed minimal to nonexistent immunogenicity over the course of the implant lifetime. Extensive tissue integration and vascularization was observed histologically within the MAP gel group by immunofluorescence staining. Mucosal wave was not impaired by any of the injected materials, including the MAP gel augmentation. Conclusions MAP gel is a nonresorbable biostimulatory injectable implant that provides superior tissue integration, stiffness matching, and permanence compared to current injectable implants, with retained biomechanical function, suggesting its potential as a new therapeutic for glottic incompetence. Level of Evidence NA Laryngoscope, 130:2432–2441, 2020
Background: Acellular dermal matrices have revolutionized alloplastic breast reconstruction. Furthering our knowledge of their biointegration will allow for improved design of these biomaterials. The ideal acellular dermal matrix for breast reconstruction would provide durable soft-tissue augmentation while undergoing rapid biointegration to promote physiologic elasticity and reduced infectious complications. The inclusion of fenestrations in their design is thought to promote the process of biointegration; however, the mechanisms underlying this theory have not been evaluated. Methods: Biointegration of standard and fenestrated acellular dermal matrices was assessed with serial photoacoustic microscopic imaging, in a murine dorsal skinfold window chamber model specifically designed to recapitulate the microenvironment of acellular dermal matrix–assisted alloplastic breast reconstruction. Photoacoustic microscopy allows for a serial, real-time, noninvasive assessment of hemoglobin content and oxygen saturation in living tissues, generating high-resolution, three-dimensional maps of the nascent microvasculature within acellular dermal matrices. Confirmatory histologic and immunohistochemical assessments were performed at the terminal time point. Results: Fenestrated acellular dermal matrices demonstrated increased fibroblast and macrophage lineage host cell infiltration, greater mean percentage surface area vascular penetration (21 percent versus 11 percent; p = 0.08), and greater mean oxygen saturation (13.5 percent versus 6.9 percent; p < 0.05) than nonfenestrated matrices by 2 weeks after implantation. By 21 days, host cells had progressed nearly 1 mm within the acellular dermal matrix fenestrations, resulting in significantly more vascularity across the top of the fenestrated matrix (3.8 vessels per high-power field versus 0.07 vessels per high-power field; p < 0.05). Conclusions: Inclusion of fenestrations in acellular dermal matrices improves the recellularization and revascularization that are crucial to biointegration of these materials. Future studies will investigate the optimal distance between fenestrations.
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