Vocal fold tissue engineering and sensors for physiological monitoring

拟议的研究项目旨在开发新的组织工程方法和听诊器，以改进声音、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，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柔软的组织和器官，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，因为它们含有纤维蛋白，如胶原蛋白。声音、呼吸和血液流动的动态导致表面弯曲或瑞利波、剪切波或压缩声波，这些声波高度阻尼并通过空气组织或血液组织界面以及通过身体的骨骼组成部分散射。该计划的第一个目标是更好地理解纤维复合水凝胶的力学。胶原I和胶原III原纤维将在溶液中使用胶原分子合成，并使用原子力显微镜测量其弹性性能。这些胶原原纤维将被纳入壳聚糖水凝胶基质的组成中，以改善细胞的招募和迁移，这在以前发现的均质散装凝胶中是不够的。该计划将通过一系列力学测试进一步开发、测试和优化纤维复合水凝胶。本文将测试一种用于声带伤口闭合的新型组织胶粘剂的粘接强度和韧性。该计划的第二个目标是使用微创加速度计阵列来捕捉人体多个身体部位的生理声音的声学特征。捕获的信号频率比主要用于成像目的的超声波低。信号处理方法将用于减少背景噪声，以突出原始数据中感兴趣的有效成分。机器学习和数据挖掘技术将用于表征、识别和诊断正常和患病的声音，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，可以量化声音使用以防止声音创伤的声速剂量计，或者可以帮助描述病理性心脏状况的听诊器。我们的复合壳聚糖-乙二醇/乙二醛/胶原支架为软组织的修复和重建提供了永久治疗的前景，特别是声带固有层，用于恢复萎缩或结节、息肉或其他病变消融后的语音功能。这项拟议中的研究将有助于创造新的医疗保健技术，使患有声音和其他涉及软器官功能障碍的残疾的加拿大人受益。

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.