Hybrid scaffold gel for the treatment of 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变的医疗和手术选择非常有限，这主要是由于尚未开发用于声带固有层细胞外基质（ECM）重建和再生的最佳手术植入生物材料。这种材料应具有与固有层ECM相似的生物力学性质和振动性质，以促进声带的功能性发声性能。它还应该能够促进新组织形成和建设性重塑，以及模拟声带ECM的复杂组成。在我们以前的研究中，我们开发了一种新的脱细胞的异种组织工程支架来源于牛声带固有层。此外，我们已经成功地制造了凝胶形式的ECM支架，这确保了其微创植入。为了进一步调整支架凝胶的生物力学和生物化学性质，我们将测试在ECM支架凝胶中掺入透明质酸（HA）以产生具有可调粘弹性和可调HA含量的混合凝胶的概念。本项目的目标是探索这种新型可注射材料（ECM-HA凝胶）用于声带固有层再生的潜力，特别是在维持和恢复功能振动性能的正常粘弹性方面。在建议的资助期内，我们会先测量不同HA浓度的ECM-HA凝胶的粘弹性。然后，在体内和体外生物相容性的混合凝胶将检查。我们将确定ECM-HA凝胶在兔模型中诱导声带损伤前即刻植入固有层时在体内预防声带瘢痕形成的功效。我们还将探索ECM-HA凝胶治疗慢性声带瘢痕的潜力，当它被植入兔模型损伤后6个月的固有层时。将使用定量方法来比较不同时间点治疗的声带与对侧未治疗的受损声带的组织成分、粘弹性特性、振动模式。在本研究中，我们将检验一种由溶解的脱细胞声带固有层细胞外基质和透明质酸组成的可注射凝胶可用于体内受损声带固有层的手术重建的总体假设。

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 and regeneration 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 promote new tissue formation and constructive remodeling as well as simulate the complex composition of the vocal fold ECM. In our previous studies, we developed a novel acellular, xenogeneic tissue engineering scaffold derived from bovine vocal fold lamina propria. Furthermore, we have successfully manufactured the ECM scaffold in a gel form which ensures its minimally invasive implantation. To further adjust the biomechanical and biochemical properties of the scaffold gel, we will test the concept of incorporating hyaluronic acid (HA) in the ECM scaffold gel to create a hybrid gel with tunable viscoelasticity and adjustable HA content. The goal of this project is to explore the potential of this novel injectable material (ECM-HA gel) for vocal fold lamina propria regeneration specifically in terms of the maintenance and restoration of normal viscoelasticity for functional vibratory performance. For the proposed funding period, we will first measure the viscoelasticity of the ECM-HA gel with different HA concentrations. Then in vivo and in vitro biocompatibility of the hybrid gels will be examined. We will determine the efficacy of the ECM-HA gel for the prevention of vocal fold scarring in vivo, when it is being implanted into the lamin propria immediately before induced vocal fold injury in a rabbit model. We will also explore the potential of the ECM-HA gel for the treatment of chronic vocal fold scarring, when it is implanted into the lamina propria six months after injury in the rabbit model. Quantitative methodologies will be used to compare the tissue compositions, viscoelastic properties, vibration patterns of the treated vocal fold at different time points to those of the contralateral untreated injured vocl fold. In the proposed studies, we will test the overall hypothesis that an injectable gel consistin of solubilized acellular vocal fold lamina propria extracellular matrix and hyaluronic acid can be used for surgical reconstruction of damaged vocal fold lamina propria in vivo.