Xenogeneic scaffolds for the repair of acute vocal fold lamina propria injury

描述(由申请人提供)：可用于治疗以声带固有层组织损伤和缺陷为特征的喉部病理的内科和外科选择非常有限，这主要是由于用于重建声带固有层细胞外基质(ECM)的最佳、可手术植入的生物材料尚未开发。这种材料应该具有与固有层ECM相似的生物力学特性和振动特性，以促进声带的功能发声表演。它还应该能够模拟声带ECM的复杂成分，并提供相对持久的增强，同时允许新的组织形成和建设性重塑。在我们的初步研究中，我们开发了一种来自牛声带固有层的新型脱细胞异种组织工程支架。该项目的主要目标是检测这种生物ECM支架的体内潜力，特别是在预防和减少固有层疾病方面，以及维持和恢复固有层ECM的正常粘弹性以实现功能性振动性能方面。在拟议的资助期内，我们将重点确定牛脱细胞支架在体内预防声带瘢痕形成的效果，即在兔模型中，将其植入声带损伤后的固有层。此外，我们将探索牛去细胞支架在体内治疗声带瘢痕的潜力，在兔模型中，将其植入损伤后三天的固有层中。定量方法将用来比较不同时间点处理的声带的组织组成、蛋白质组织和粘弹性特性，以及对侧完整或未处理的损伤声带的组织组成、蛋白质组织和粘弹性特性。在拟议的研究中，我们将检验从牛声带固有层衍生的生物脱细胞ECM支架可以用作体内声带固有层损伤的外科重建的植入性组织替代品的总体假设。 与公共健康相关：据估计，每年有3%-9%的美国人患有某种语音障碍，这些疾病对沟通能力、生活质量、甚至依赖健康、功能健全的嗓音作为其职业的个人的职业生涯都产生了不利影响。尽管近年来在声外科方法和治疗策略方面取得了进展，但由于声带固有层易受瘢痕组织形成的影响以及难以有效地替代固有层，声带固有层的缺陷，如声带瘢痕、萎缩和声沟，仍然是临床上最具挑战性的疾病之一。这项拟议的研究探索了一种创新的组织工程支架的潜力，以促进受损声带固有层的功能重建，并可能有助于开发有效的手术治疗此类嗓音障碍。

DESCRIPTION (provided by applicant): Very limited medical and surgical options are available for treating laryngeal pathologies characterized by tissue damage and deficiencies in the vocal fold lamina propria, largely due to the fact that an optimal, surgically implantable biomaterial for reconstruction of the vocal fold lamina propria extracellular matrix (ECM) has yet to be developed. Such a material should have biomechanical properties and vibratory properties similar to those of the lamina propria ECM, in order to facilitate functional phonatory performance of the vocal fold. It should also be able to simulate the complex composition of the vocal fold ECM, as well as provide relatively long-lasting augmentation while allowing for new tissue formation and constructive remodeling. In our preliminary studies, we have developed a novel acellular, xenogeneic tissue engineering scaffold derived from the bovine vocal fold lamina propria. The overarching goal of this project is to examine the in vivo potential of this biological ECM scaffold, specifically in terms of the prevention and reduction of lamina propria disorders, and the maintenance and restoration of normal viscoelasticity of the lamina propria ECM for functional vibratory performance. For the proposed funding period, we will focus on determining the efficacy of the bovine acellular scaffold for the prevention of vocal fold scarring in vivo, when it is being implanted into the lamina propria immediately after induced vocal fold injury in a rabbit model. Furthermore, we will explore the potential of the bovine acellular scaffold for the treatment of vocal fold scarring in vivo, when it is being implanted into the lamina propria three days after injury in the rabbit model. Quantitative methodologies will be used to compare the tissue composition, protein organization, and viscoelastic properties of the treated vocal fold at different time points to those of the contralateral intact or untreated injured vocal fold. In the proposed studies, we will test the overall hypothesis that the biological acellular ECM scaffold derived from the bovine vocal fold lamina propria can be used as an implantable tissue substitute for surgical reconstruction of the damaged vocal fold lamina propria in vivo. PUBLIC HEALTH RELEVANCE: Each year, an estimated 3-9% of Americans suffer from some kind of voice disorders, which adversely affect the communicative abilities, quality of life, and even the careers of individuals relying on a healthy, functional voice for their occupations. Despite the recent advances in phonosurgical approaches and therapeutic strategies, vocal fold lamina propria defects, such as vocal fold scarring, atrophy and sulcus vocalis, remain to be among the most clinically challenging disorders, due to the vulnerability of the vocal fold lamina propria to scar tissue formation and the difficulties to effectively replace the lamina propria. The proposed research explores the potential of an innovative tissue engineering scaffold to facilitate the functional reconstruction of the injured vocal fold lamina propria, and could contribute to the development of effective surgical management for such voice disorders.