Hybrid scaffold gel for the treatment of vocal fold lamina propria injury

用于治疗声带固有层损伤的混合支架凝胶

• 批准号: 8702485
• 负责人: Chet Che Xu
• 金额: $ 23.85万
• 依托单位: UT SOUTHWESTERN MEDICAL CENTER
• 依托单位国家: 美国
• 财政年份: 2014
• 资助国家: 美国
• 起止时间: 2014-04-01 至 2016-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8702485
• 关键词: Affect; American; Atrophic; Autologous; Biochemical; Biocompatible Materials; Biological; Biomechanics; Cattle; Cell Culture Techniques; Cell Survival; Cell Therapy; Chemicals; Chronic; Cicatrix; Collagen; Complex; Contralateral; Defect; Development; Disadvantaged; Ensure; Extracellular Matrix; Fatty acid glycerol esters; Fibroblasts; Fibrosis; Funding; Gel; Goals; Growth Factor; Harvest; Histologic; Human; Hyaluronic Acid; Hybrids; Hydrogels; Image; Immune response; Immunoglobulin G; Immunoglobulin M; Implant; In Vitro; Individual; Injectable; Injection of therapeutic agent; Injury; Lamina Propria; Lamins; Larynx; Lead; Maintenance; Measures; Medical; Methodology; Modeling; Molecular; Motivation; Natural regeneration; Occupations; Operative Surgical Procedures; Oryctolagus cuniculus; Pathology; Patients; Pattern; Performance; Phonation; Prevention; Process; Production; Property; Proteins; Quality of life; Regenerative Medicine; Research; Saline; Serum; Simulate; Site; Speed; Staging; Surgical Management; Testing; Therapeutic; Time; Tissue Engineering; Tissues; Voice; Voice Disorders; Wound Healing; base; biomaterial compatibility; career; crosslink; implantation; improved; in vivo; injured; innovation; minimally invasive; novel; novel therapeutic intervention; public health relevance; reconstruction; research study; restoration; scaffold; three dimensional structure; vibration; viscoelasticity; vocal cord; vocalis muscle

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.

描述(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，这主要是由于用于声带固有层细胞外基质(ECM)重建和再生的最佳、外科可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。它还应该能够促进新的组织形成和建设性的重塑，以及模拟声带ECM的复杂成分。在我们之前的研究中，我们开发了一种新型的脱细胞异种组织工程支架，来源于牛声带固有层。此外，我们还成功地制作了凝胶形式的ECM支架，以确保其微创植入。为了进一步调整支架凝胶的生物力学和生化性能，我们将测试在ECM支架凝胶中加入透明质酸(HA)的概念，以创建一种粘弹性可调、HA含量可调的杂化凝胶。本项目的目的是探索这种新型可注射材料(ECM-HA凝胶)在声带固有层再生方面的潜力，特别是在维持和恢复正常粘弹性以进行功能性振动表演方面。在拟议的资助期内，我们将首先测量不同HA浓度的ECM-HA凝胶的粘弹性。然后对杂化凝胶的体内和体外生物相容性进行检测。我们将确定ECM-HA凝胶在体内预防声带瘢痕形成的效果，当它被植入兔模型声带损伤之前的固有层。我们还将探索ECM-HA凝胶在治疗慢性声带瘢痕形成方面的潜力，当它在损伤后6个月被植入兔模型的固有层中时。我们将使用定量方法来比较不同时间点处理后的声带与未处理的对侧声带的组织成分、粘弹性、振动模式。在拟议的研究中，我们将检验一个总体假设，即由可溶解的无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外科重建。