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

项目总结/摘要 在任何特定的时间点，3%到9%的普通人口都有声音问题。等 这些问题会产生严重的心理、功能和经济后果，特别是对教师而言， 专业语音用户。影响嗓音的最严重的情况是声带粘膜丧失或 由Scar取代。对于大的粘膜空隙或瘢痕，我们建议将有效的生物材料输送到 声带部位使用内窥镜适合手持生物打印机。这种方法可以帮助再生功能性的 声带组织和恢复发声。仿生自愈合水凝胶的作用就像流体流动， 当前体混合时，针头挤出并迅速固化，从而允许声带原位沉积 通过挤压植入。我们将优化一种自我修复的水凝胶配方，该配方能够快速粘附和密封， 宿主组织，其中苯酚基组分由于其生物相容性将用作粘合剂 和可调的粘合强度。我们将使用人体试验评估所提出的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长度， 同轴几何形状我们将探索生物打印策略，通过改变细胞的生长方式来存款这种声带植入物。 在手持式生物打印机中的设计参数和将所提出的水凝胶挤出到声带部位。我们 将使用体外喉测试我们的手持式生物打印机，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。 我们提出的手持式生物打印机的效率。我们的首要目标是将所提出的自我修复 水凝胶系统和生物打印平台进入美国的耳鼻喉科诊所， 成功完成了这一任务。

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.