Tissue Engineering of Vocal Fold Lamina Propria

声带固有层的组织工程

• 批准号: 7901285
• 负责人: Xinqiao Jia
• 金额: $ 9.75万
• 依托单位: UNIVERSITY OF DELAWARE
• 依托单位国家: 美国
• 财政年份: 2009
• 资助国家: 美国
• 起止时间: 2009-08-14 至 2010-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7901285
• 关键词: Adhesives; Affect; Basement membrane; Behavior Therapy; Biochemical; Biologic Characteristic; Biological; Biomechanics; Biomimetics; Bioreactors; Cell Adhesion; Cell Proliferation; Cells; Characteristics; Chemistry; Cicatrix; Connective Tissue; Cues; Development; Disease; Dysphonia; Encapsulated; Environment; Epithelium; Extracellular Matrix; Fiber; Fibroblasts; Figs - dietary; Fostering; Frequencies; Functional disorder; Ground Substance; Growth Factor; Hand; Hematoxylin and Eosin Staining Method; Hoarseness; Human; Hyaluronic Acid; Hydrogels; In Situ; In Vitro; Individual; Injectable; Lamina Propria; Lead; Length; Mechanical Stimulation; Mechanical Stress; Mechanics; Methods; Natural regeneration; Newborn Infant; Peptides; Pharmaceutical Preparations; Phenotype; Play; Pliability; Polymers; Production; Property; Recovery; Research; Role; Shapes; Staging; Staining method; Stains; Stimulus; Stress; Structure; Surface; Symptoms; Therapeutic; Tissue Engineering; Tissues; Trachea; Treatment Protocols; Voice; Water; alternative treatment; base; crosslink; design; experience; flexibility; functional restoration; improved; in vivo regeneration; morphogens; particle; physical property; prevent; scaffold; sound; viscoelasticity; vocal cord; vocalis muscle

DESCRIPTION (provided by applicant): Human voice production is dependent on the flexible vocal fold lamina propria that can vibrate when brought together while being driven by the airstream from the trachea. Voice overuse or abuse can lead to scarring that disrupts the natural pliability of the lamina propria and results in hoarseness and other symptoms of vocal dysfunction. The reduction of vocal fold scarring remains a significant therapeutic challenge. We propose to develop two parallel tissue engineering approaches that will lead to the regeneration of vocal fold lamina propria. The first method will apply injectable hydrogels to prevent scar formation, improve the pliability of damaged tissue, initiate active tissue remodeling, and ultimately, afford in vivo regeneration of functional vocal fold lamina propria. The second approach relies on in vitro functional tissue formation by the appropriate combination of cells, artificial extracellular matrices (ECM), biological cues and mechanical stimuli. We are developing artificial ECM based on crosslinked particle networks (XPN) that consist of hyaluronic acid (HA) hydrogel particles (HGP) and water soluble functional polymers. The hydrogel particles are designed to exhbit controlled sizes, defined surface functionality, improved enzymatic stability, and spatial/temporal display of biologically active molecules including antifibrotic drugs, growth factor morphogens and cell adhesion peptides. The XPN, on the other hand, will have tunable viscoelasticty and controlled degradation that capture the mechanical and biological characteristics of the native lamina propria. The existence of two levels of crosslinking (within and between individual HGP) offers potential for rapid recovery from mechanical stress. The crosslinking chemistry is designed to allow for in situ encapsulation of vocal fold fibroblasts (VFF). To mimic the mechanical environment experienced by the vocal fold tissue, we propose to construct a bioreactor that is capable of delivering well-defined vibrational and tensile stresses to the cell-encapsulated scaffolds. The combination of vocal fold fibroblasts, elastic and bioactive artificial ECM, and a dynamtic bioreactor offers exciting opportunity for in vitro tissue engineering of vocal fold lamina propria.

描述（由申请人提供）：人类发声取决于灵活的声带固有层，当声带固有层在气管气流驱动下聚集在一起时会振动。过度使用或滥用声音会导致疤痕，破坏固有层的自然柔韧性，并导致声音嘶哑和其他声音功能障碍症状。减少声带疤痕仍然是一个重大的治疗挑战。我们建议开发两种并行的组织工程方法，以实现声带固有层的再生。第一种方法将应用可注射水凝胶来防止疤痕形成，改善受损组织的柔韧性，启动主动组织重塑，并最终实现功能性声带固有层的体内再生。第二种方法依赖于通过细胞、人工细胞外基质（ECM）、生物信号和机械刺激的适当组合来形成体外功能组织。我们正在开发基于交联颗粒网络 (XPN) 的人工 ECM，该网络由透明质酸 (HA) 水凝胶颗粒 (HGP) 和水溶性功能聚合物组成。水凝胶颗粒的设计目的是表现出受控的尺寸、明确的表面功能、改进的酶稳定性以及生物活性分子的空间/时间展示，包括抗纤维化药物、生长因子形态发生素和细胞粘附肽。另一方面，XPN 将具有可调节的粘弹性和受控的降解，从而捕获天然固有层的机械和生物特征。两个交联水平的存在（单个 HGP 内部和之间）提供了从机械应力中快速恢复的潜力。交联化学旨在允许原位封装声带成纤维细胞 (VFF)。为了模拟声带组织所经历的机械环境，我们建议构建一个生物反应器，能够向细胞封装的支架传递明确的振动和拉伸应力。声带成纤维细胞、弹性和生物活性人工 ECM 以及动态生物反应器的结合为声带固有层的体外组织工程提供了令人兴奋的机会。