Biodegradable elastic patches for congenital diaphragmatic hernia treatment

用于治疗先天性膈疝的可生物降解弹性补片

• 批准号: 10353597
• 负责人: Yi Hong
• 金额: $ 24.68万
• 依托单位: UNIVERSITY OF TEXAS ARLINGTON
• 依托单位国家: 美国
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-07-19 至 2024-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10353597
• 关键词: Abdomen; Abdominal Cavity; Address; Adult; Affect; Age; Biomechanics; Birth; Blood Vessels; Cells; Chest; Child; Clinical; Congenital Abnormality; Congenital diaphragmatic hernia; Defect; Development; Elastic Tissue; Elasticity; Electrospinning; Ethnic Origin; Evaluation; Extracellular Matrix; Family suidae; Fetal Development; Fetal Lung; Goretex; Growth; Heart; Heart Valves; Hernia; Impairment; Intervention; Intestines; Left; Liver; Lung; Mechanics; Membrane; Meniscus structure of joint; Mesenchymal Stem Cells; Methodology; Methods; Modeling; Morbidity - disease rate; Movement; Muscle; Muscle Cells; Names; Natural regeneration; Newborn Infant; Operative Surgical Procedures; Organ; Polyethylenes; Polymers; Polypropylenes; Polytetrafluoroethylene; Polyurethanes; Process; Prosthesis; Pulmonary Hypertension; Race; Rattus; Recurrence; Regenerative capacity; Repair Material; Respiration; Respiratory Diaphragm; Rodent Model; Side; Silastic; Skin; Small Intestinal Submucosa; Sprague-Dawley Rats; Stomach; Structural Congenital Anomalies; Structure of parenchyma of lung; Supporting Cell; Surgical Models; Surgical sutures; Time; Tissues; United States; amnion; base; biomaterial compatibility; bioscaffold; cell growth; fetal; improved; in vivo; in vivo evaluation; innovation; lung development; mechanical properties; mortality; neonatal care; novel; novel therapeutic intervention; novel therapeutics; poly(lactide); postnatal; pulmonary hypoplasia; recruit; regeneration potential; regenerative; regenerative tissue; repaired; reparative capacity; scaffold

Project summary Congenital diaphragmatic hernia (CDH) is a serious birth defect characterized by incomplete development of the diaphragm. This results in a defect in the diaphragm through which abdominal organs, such as the intestines and stomach, can herniate into the chest. This can cause compression of the lungs and impairs their development, which can result in fatal pulmonary hypoplasia. CDH affects all races and ethnicities. In the United States alone, five children are born with this birth defect every day, and one of every three newborns with this devastating condition dies. CDH treatment requires surgical intervention to return the herniated organs to the abdominal cavity and to repair the defect. In some cases, the defect in the diaphragm can be closed by suturing the diaphragm edges together. However, if the defect is too large or if portions of the diaphragm are completely missing, a prosthetic patch must be used to fix the defect. These patches are most made of synthetic, biologically inert/inactive materials like polypropylene mesh, reinforced silastic sheet, polyethylene mesh and polytetrafluoroethylene (trade name Gore-Tex). However, as synthetic patches do not grow with the child, dehiscence and recurrent herniation are common. Biodegradable synthetic patches, such as polylactide, are mechanically incompliant and possess insufficient regenerative potential. Decellularized tissue patches, such as small intestinal submucosa (SIS) and decellularized diaphragm, are mechanically weak and degrade rapidly. To address these problems, we aim to develop a novel biodegradable, bioactive, elastic patch that not only matches the mechanical properties of the native diaphragm but also comes with regenerative potential for CDH repair. Specifically, a biodegradable elastic polymer and decellularized porcine diaphragm will be combined to form a fibrous patch. The polymer will provide robust mechanical support with elasticity and controllable degradation while the decellularized diaphragm extracellular matrix (ECM) will offer diaphragm tissue-specific bioactivity to support cell and tissue growth. This novel patch will be able to move with respiration along with the native diaphragm and more importantly will grow with the child. Two aims are proposed in this study. In Aim 1, we will systematically characterize the biomechanics and bioactivity of the native diaphragm, and then develop a fibrous patch that contains diaphragm-specific ECM bioactivity and mechanically matches the native diaphragm. In Aim 2, we will use an established surgically created diaphragmatic defect rat model to evaluate the in vivo and ex vivo diaphragmatic functions of the novel patch. This project is innovative and translational, as successful completion of this project will establish a new methodology to generate a biodegradable, elastic and bioactive diaphragmatic patch, and provide a novel therapeutic strategy to treat children born with CDH.

项目摘要 先天性diaphragmaratic疝（CDH）是严重的出生缺陷，其特征是不完整的发展 膜片。这会导致diaphragm的缺陷，腹部器官（例如肠） 和胃，可以疝气进入胸部。这会导致肺部压缩并损害他们的 发育，这可能导致致命的肺部发育不全。 CDH影响所有种族和种族。在曼联 仅州，五个孩子每天都有这种出生缺陷，而这三个新生儿之一 毁灭性的状态死亡。 CDH治疗需要手术干预才能将椎骨器官归还给 腹腔并修复缺陷。在某些情况下，隔膜中的缺陷可以通过缝合来封闭 隔膜一起边缘。但是，如果缺陷太大，或者部分的部分是完全 缺少，必须使用假肢来解决缺陷。这些斑块最由合成，生物学制成 惰性/非活性材料，例如聚丙烯网，增强的硅胶片，聚乙烯网和 Polytetrafluoroethelene（商标名称Gore-Tex）。但是，由于合成斑块不会随着孩子而生长， 开裂和复发性疝是常见的。可生物降解的合成斑（例如多乳酸化剂）是 机械上不公开，没有足够的再生潜力。脱细胞组织斑块，例如 小肠粘膜（SIS）和脱细化的隔膜在机械上较弱，并且迅速降解。到 解决这些问题，我们旨在开发一种可生物降解，生物活性，弹性贴片，不仅与 天然隔膜的机械性能，但还具有CDH修复的再生潜力。 具体而言，将将可生物降解的弹性聚合物和脱细胞化猪膜片组合在一起以形成A 纤维斑。聚合物将提供弹性和可控降解的强大机械支持 磁性隔膜外基质（ECM）将提供隔膜组织特异性生物活性 支持细胞和组织生长。这个小说的补丁将能够与本地人一起呼吸移动 隔膜，更重要的是，孩子会随着孩子的身份增长。这项研究提出了两个目标。在AIM 1中，我们将 系统地表征天然隔膜的生物力学和生物活性，然后发展纤维 包含隔膜特异性ECM生物活性并机械匹配天然隔膜的贴片。目标 2，我们将使用已建立的手术创建的diaphragmatic缺陷大鼠模型来评估体内和EX 新斑块的体内dia肌功能。这个项目具有创新性和转化性 该项目的完成将建立一种新方法，以生成可生物降解，弹性和生物活性 diaphragmatic斑块，并提供了一种新颖的治疗策略来治疗患有CDH的孩子。