Handheld 3D Bioprinting of Self-Healing Hydrogels for Vocal Fold Reconstruction

项目摘要/摘要 在任何给定的时间点上，3%到9%的普通人群都有嗓音问题。是这样的 问题具有严重的心理、功能和经济后果，特别是对教师和 专业语音用户。影响嗓音的最严重的情况是声带粘膜丢失或 换成了刀疤。对于较大的粘膜空洞或疤痕，我们建议将有效的生物材料输送到 声带部位使用适合内窥镜检查的手持生物打印机。此方法可能有助于重新生成功能 声带组织和恢复发声。仿生自我修复水凝胶在过程中表现为流体流动 当前体混合时，针被挤出并迅速凝固，从而允许声带在原位沉积 通过挤压进行植入物。我们将优化一种自我修复水凝胶配方，使其能够快速黏附和密封 宿主组织，其中基于苯酚的成分由于其生物兼容性将被用作粘合剂 和可调的粘接强度。我们将在人体内评估这种水凝胶的生物相容性。 声带成纤维细胞。水凝胶将为定制的手持生物打印机提供可调的长度和 同轴几何图形。我们将探索生物打印策略，通过改变 手持式生物打印机中的设计参数和将所建议的水凝胶挤出到声带部位。我们 将使用体外喉部测试我们的手持生物打印机，并将优化沉积参数。在 最后一步，我们将结合动物模型对我们的水凝胶进行体内评估，并证明临床应用的合理性。 我们提议的手持式生物打印机的效率。我们的首要目标是将提议的自我修复 水凝胶系统和生物打印平台进入美国的耳鼻喉科诊所 成功完成此拨款。

PROJECT SUMMARY/ABSTRACT Between 3% and 9% of the general population have a voice problem at any given point in time. Such problems have serious psychological, functional and economic consequences, in particular for teachers and professional voice users. The most severe conditions affecting voice are when vocal fold mucosa is lost or replaced by scar. For large mucosa voids or scarring, we propose to deliver effective biomaterials into the vocal fold site using an endoscopy-fit handheld bioprinter. This approach may help regenerate a functional vocal fold tissue and restore voice production. Biomimetic self-healing hydrogels act like fluid flow during needle extrusion and rapidly solidify when the precursors mix, thus allowing in situ deposition of vocal fold implants via extrusion. We will optimize a self-healing hydrogel formulation that adheres and seals quickly to the host tissue, in which phenol-based components will be used as adhesives due to their biocompatibility and tunable adhesion strength. We will assess the biocompatibility of the proposed hydrogel using human vocal fold fibroblasts. The hydrogel will feed a custom-made handheld bioprinter with tunable length and coaxial geometry. We will explore bioprinting strategies to deposit such vocal fold implants via changing design parameters in the handheld bioprinter and extrusion of the proposed hydrogel to vocal fold sites. We will test our handheld bioprinter using ex vivo larynges, and will optimize the deposition parameters. In the last step, we will incorporate an animal model for in vivo assessment of our hydrogel and to justify the clinical efficiency of our proposed handheld bioprinter. Our overarching goal is to translate the proposed self-healing hydrogel system and the bioprinting platform into otolaryngology clinics in the United States when we successfully complete this grant.