Bioprintable composite materials and microfluidic tools for vocal fold restoration and repair

项目总结/摘要： 语音障碍是整个生命周期中最常见的沟通障碍之一。约3- 9%的普通人群，包括儿童和成人，在任何给定的时间点都有声音问题。我们 最终目的是永久修复受伤，改变或功能障碍的声带组织， 用于病变特异性应用的生物材料。许多先前关于用于VF修复的可注射生物材料的工作， 通过针头进行靶向皮下注射。这种递送方法可用于外科治疗 允许针头注射到原生LP或肌肉中以进行VF介导的病理。我们有 开发了复合生物活性组织工程生物材料，即乙二醇-壳聚糖（GCS）水凝胶， 包埋胶原纤维（COL I+III.在过去一年，我们的小组已改善了政府统计处的组成 水凝胶转化为高度多孔的粘弹性水凝胶（PVH）。PVH的增加的孔隙率预期将增强 从而加速内源性组织再生。我们已经完成了一 使用PVH的可注射形式的一系列体外实验。 我们建议建立新的生物打印工具，可以提供生物材料来现场包扎伤口。当大 使用冷刀或激光手术切除诸如癌症的病变，可能会产生大的空隙， 从腰椎穿刺一直到肌肉新型材料，固化，粘附和密封迅速原位将是 是为了防止脱落和被吸入呼吸道而开发的。我们提出了一种快速聚合材料， PVH-prt，在几秒钟内治愈，而不是几分钟，并且可以通过喉镜现场打印 使用针头大小的喷嘴。现场逐层沉积和雕刻将重建切除部分 VF采用机械坚韧、粘合强度高、固化速度快的新材料。 我们将研究使用基于以下的增材制造工具来放置这种植入物的策略： 微流体技术我们将使用离体喉部测试定制的内窥镜尺寸手术“3D打印笔”， VF副本。我们将使用动物模型在体内对这种新概念进行初步研究。 我们将在家兔中评价我们的生物材料。异物反应、组织粘弹性和发声 将分别用组织学、机械测试和流动台实验评价功能。到 补充动物研究的已知限制，并建立在以前的研究，拟声生物反应器 将被用来系统地改变支架的性质，类型和发声条件，并评估 工程化固有层的机械特性。我们的首要目标是将这些新的 生物材料和生物打印工具在未来5年内进入美国和加拿大的耳鼻喉科诊所 年

PROJECT SUMMARY/ABSTRACT: Voice disorders are among the most common communication disorders across the lifespan. Approximately 3- 9% of the general population, including children and adults, have a voice problem at any given point in time. Our ultimate aim is the permanent repair of injured, altered or dysfunctional vocal fold tissue using injected or printed biomaterials for lesion-specific application. Much previous work on injectable biomaterials for VF repair has targeted sub-epithelial injections through a needle. Such delivery method is useful for the surgical treatment of pathologies allowing needle injection into the native LP, or into the muscle for VF medialization. We have developed composite bioactive tissue-engineered biomaterials, namely glycol-chitosan (GCS) hydrogels with imbedded collagen fibers (COL I+III. Within the past year, our group has refined the composition of the GCS hydrogel to a highly porous viscoelastic hydrogel (PVH). The increased porosity of PVH is expected to enhance infiltration and survival of host cells and thus accelerate endogenous tissue regeneration. We have completed a series of in vitro experiments using an injectable form of PVH. We propose to build novel bioprinting tools that can deliver biomaterials to dress wounds on site. When large lesions such as cancer are surgically removed using cold knifes or lasers, large voids are created possibly all the way through the LP, down to the muscle. Novel materials that cure, adhere and seal quickly in situ will be developed to prevent being dislodged and ingested into the airway. We propose a fast polymerization material, PVH-prt, that cures in seconds, as opposed to minutes, and that can be printed on site through a laryngoscope using needle-sized nozzles. On-site layer-by-layer deposition and sculpting would rebuild the resected portion of the VF using new materials that are mechanically tough, with high adhesive strength, and that solidify quickly. We will investigate strategies to lay such implants using additive manufacturing tools that are based on microfluidics. We will test custom-made endoscopic size surgical “3D printing pens” using ex vivo larynges and VF replicas. We will perform pilot studies of this novel concept in vivo using an animal model. We will evaluate our biomaterials in rabbits. Foreign body response, tissue viscoelasticity and phonatory functions will be evaluated with histology, mechanical tests and flow-bench experiments, respectively. To complement the known limitations of animal studies and build on previous studies, a phonomimetic bioreactor will be used to systematically vary scaffold properties, types and phonation conditions, and assess the mechanical characteristics of the engineered lamina propria. Our overarching goal is to translate these new biomaterials and bioprinting tools into otolaryngology clinics in the United States and Canada within the next 5 years.