Vocal fold tissue engineering and sensors for physiological monitoring

拟议的研究计划旨在开发新的组织工程方法和听诊器，以提高对嗓音、呼吸和心血管疾病的诊断和治疗，这些疾病普遍存在，影响很大一部分人口，但需要付出高昂的社会经济成本。这些生理问题主要是由相对较软的组织和器官，即声带、肺和心脏的功能障碍引起的。这些软组织是高度各向异性的，因为它们含有胶原等纤维蛋白。声音、呼吸和血流的动力学导致表面弯曲或瑞利波、剪切波或压缩声波，这些波被高度衰减并散射到空气-组织或血液-组织界面以及身体的骨骼组件中。拟议计划的第一个目标是更好地了解纤维状复合水凝胶的机理。将使用原胶原分子在溶液中合成I型和III型胶原纤维，并将使用原子力显微镜测量它们的弹性性能。这些胶原纤维将被结合到壳聚糖水凝胶基质的组合物中，以改善细胞的募集和迁移，这在以前发现在均质块状凝胶中是不够的。该计划将通过一系列力学测试进一步开发、测试和优化纤维状复合水凝胶。将测试一种用于关闭声带伤口的新型组织粘合剂的粘合强度和韧性。该计划的第二个目标是使用微创加速度计阵列来捕获身体多个位置的生理声音的声学特征。捕获的信号频率低于主要用于成像目的的超声波。将使用信号处理方法来降低背景噪声，以便在原始数据中突出感兴趣的有效分量。机器学习和数据挖掘技术将被用于表征、识别和诊断正常和疾病的声音，以及呼吸和心脏功能障碍。拟议的研究计划将有助于建立诊断工具和健康监测设备，例如可以量化语音使用以防止声音创伤的音量计，或有助于表征病理性心脏疾病的听诊器。我们的壳聚糖-乙二醇/乙二醛/胶原复合支架为软组织，特别是声带固有层的修复和重建提供了一种永久性治疗方法，用于在萎缩或切除结节、息肉或其他病变后恢复声音功能。这项拟议的研究将有助于创造新的医疗保健技术，使加拿大患有声音和其他与软器官功能障碍有关的残疾的人受益。

The proposed research program aims at the development of novel tissue engineering methods and stethoscopes that may lead to improved diagnosis and treatment of voice, respiratory, and cardiovascular disorders, which are pervasive and affect a large fraction of the population, at high socioeconomic costs. These physiological problems are mainly caused by the malfunction of relatively soft tissues and organs, namely vocal folds, lungs and heart. These soft tissues are highly anisotropic, as they contain fibrillary proteins such as collagen. The dynamics of voice, respiration and blood flow result in surface bending or Rayleigh waves, shear waves, or compressional acoustic waves that are highly damped and scattered through air-tissue or blood-tissue interfaces as well as through the skeletal components of the body.The first aim of the proposed program is to gain a better understanding of the mechanics of fibrillary composite hydrogels. Collagen I and collagen III fibrils will be synthesized using tropocollagen molecules in solution and their elastic properties will be measured using atomic force microscopy. These collagen fibrils will be incorporated in the composition of a chitosan hydrogel matrix to improve cell recruitment and migration, which was previously found to be insufficient in homogeneous bulk gels. The proposed program will further develop, test and optimize the fibrillary composite hydrogels through a series of mechanical tests. The bonding strength and toughness of a novel tissue adhesive for vocal fold wound closure will be tested.The second aim of the proposed program lies on the use of minimally invasive accelerometer arrays to capture the acoustic characteristics of the body's physiological sounds at multiple body locations. The signals captured are lower in frequency than ultrasonic waves, which are used primarily for imaging purposes. Signal processing methods will be used to reduce background noise in order to protrude valid components of interest in raw data. Machine learning and data mining techniques will be used to characterize, identify and diagnose normal and diseased voice, as well as respiratory and cardiac malfunctions.The proposed research program will help to build diagnostic tools and health monitoring devices, for example a phono-dosimeter that could quantify voice use to prevent phono-trauma, or a stethoscope that could help characterize pathological heart conditions. Our composite chitosan-glycol/glyoxal/collagen scaffolds offer the prospect of a permanent treatment for repair and reconstruction of soft tissues, in particular the vocal fold lamina propria, for the restoration of voice function following atrophy or the ablation of nodules, polyps or other lesions. The proposed research will help create novel health care technologies that will benefit Canadians with voice and other disabilities involving the malfunction of soft organs.