Force-Bioreactor for Assessing Pharmacological Therapies for Mechanobiological Targets

Tissue fibrosis is a major health issue that impacts millions of people and is costly to treat. However, few effective anti-fibrotic treatments are available. Due to their central role in fibrotic tissue deposition, fibroblasts and myofibroblasts are the target of many therapeutic strategies centered primarily on either inducing apoptosis or blocking mechanical or biochemical stimulation that leads to excessive collagen production. Part of the development of these drugs for clinical use involves in vitro prescreening. 2D screens, however, are not ideal for discovering mechanobiologically significant compounds that impact functions like force generation and other cell activities related to tissue remodeling that are highly dependent on the conditions of the microenvironment. Thus, higher fidelity models are needed to better simulate in vivo conditions and relate drug activity to quantifiable functional outcomes. To provide guidance on effective drug dosing strategies for mechanoresponsive drugs, we describe a custom force-bioreactor that uses a fibroblast-seeded fibrin gels as a relatively simple mimic of the provisional matrix of a healing wound. As cells generate traction forces, the volume of the gel reduces, and a calibrated and embedded Nitinol wire deflects in proportion to the generated forces over the course of 6 days while overhead images of the gel are acquired hourly. This system is a useful in vitro tool for quantifying myofibroblast dose-dependent responses to candidate biomolecules, such as blebbistatin. Administration of 50 μM blebbistatin reliably reduced fibroblast force generation approximately 40% and lasted at least 40 h, which in turn resulted in qualitatively less collagen production as determined via fluorescent labeling of collagen

The Finite Element Simulation of the Upper Airway of Patients with Moderate and Severe Obstructive Sleep Apnea Hypopnea Syndrome

Objectives. To investigate the snoring modes of patients with Obstructive Sleep Apnea Hypopnea Syndrome and to discover the main sources of snoring in soft tissue vibrations. Methods. A three-dimensional finite element model was developed with SolidEdge to simulate the human upper airway. The inherent modal simulation was conducted to obtain the frequencies and the corresponding shapes of the soft tissue vibrations. The respiration process was simulated with the fluid-solid interaction method through ANSYS. Results. The first 6 orders of modal vibration were 12 Hz, 18 Hz, 21 Hz, 22 Hz, 36 Hz, and 39 Hz. Frequencies of modes 1, 2, 4, and 5 were from tongue vibrations. Frequencies of modes 3 and 6 were from soft palate vibrations. Steady pressure distribution and air distribution lines in the upper airway were shown clearly in the fluid-solid interaction simulation results. Conclusions. We were able to observe the vibrations of soft tissue and the modeled airflow by applying the finite element methods. Future studies could focus on improving the soft tissues vibration compliances by adjusting the model parameters. Additionally, more attention should be paid to vibrational components below 20 Hz when performing an acoustic analysis of human snore sounds due to the presence of these frequencies in this model

Simulation of Pediatric Endoscopic Cricoid Reduction and Expansion

Endoscopic cricoid expansion and reduction are newer approaches to the management of pediatric bilateral vocal fold immobility and postlaryngotracheal reconstruction glottic insufficiency, respectively. These procedures offer a less invasive, endoscopic alternative to procedures that typically required open management with a more prolonged recovery. These technically demanding procedures are currently performed only in select centers, and there is no currently described training model for practicing them. We present a modification to a laryngeal dissection station that allows for simulation of endoscopic cricoid reduction and expansion with excised larynges. The model allows trainees to practice endoscopic posterior cricoid exposure, incision of the cricoid cartilage, placement of a simulated costal cartilage graft for expansion, and endoscopic suturing for reduction. Development of simulators for procedures that are infrequently performed have the potential to help trainees reach surgical competency faster and more safely