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: 10667413
• 负责人: Yi Hong
• 金额: $ 19.44万
• 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/10667413
• 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; Trachea; United States; amnion; biomaterial compatibility; biomechanical test; bioscaffold; cell growth; fetal; implantation; 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.

项目概要 先天性膈疝（CDH）是一种严重的出生缺陷，其特征是膈肌发育不完全。 隔膜。这会导致膈肌缺损，腹部器官（例如肠）通过膈肌缺损 和胃，可疝入胸部。这可能会导致肺部受压并损害其功能 发育，这可能导致致命的肺发育不全。 CDH 影响所有种族和民族。在美国 仅在各州，每天就有五个孩子出生时患有这种先天缺陷，每三个新生儿中就有一个患有这种先天缺陷 毁灭性的情况死亡。 CDH 治疗需要手术干预以将突出的器官返回 腹腔并修复缺损。在某些情况下，隔膜中的缺陷可以通过缝合来闭合 隔膜边缘在一起。然而，如果缺陷太大或者隔膜的某些部分完全被损坏， 如果缺失，则必须使用修复补片来修复缺陷。这些贴片大部分由合成的、生物的制成 惰性/非活性材料，如聚丙烯网、增强硅橡胶板、聚乙烯网和 聚四氟乙烯（商品名 Gore-Tex）。然而，由于合成贴片不会随孩子一起成长， 裂开和复发性疝气很常见。可生物降解的合成贴剂，例如聚丙交酯， 机械不顺应且再生潜力不足。脱细胞组织补片，例如 小肠粘膜下层 (SIS) 和脱细胞隔膜的机械强度较弱且降解迅速。到 针对这些问题，我们的目标是开发一种新型的可生物降解、生物活性、弹性贴片，不仅可以匹配 它不仅具有天然隔膜的机械特性，而且还具有 CDH 修复的再生潜力。 具体来说，将可生物降解的弹性聚合物和脱细胞猪隔膜结合起来形成 纤维斑块。该聚合物将提供坚固的机械支撑，具有弹性和可控降解 而脱细胞隔膜细胞外基质（ECM）将提供隔膜组织特异性生物活性 支持细胞和组织生长。这个新颖的补丁将能够随着本地人的呼吸而移动 隔膜更重要的是会随着孩子一起成长。本研究提出了两个目标。在目标 1 中，我们将 系统地表征天然隔膜的生物力学和生物活性，然后开发纤维 贴片含有隔膜特定的 ECM 生物活性，并且在机械上与天然隔膜匹配。瞄准 2、我们将使用已建立的手术创建的膈肌缺损大鼠模型来评估体内和体外的 新型贴片的体内膈肌功能。该项目具有创新性和转化性，非常成功 该项目的完成将建立一种新的方法来产生可生物降解的、弹性的和生物活性的 膈肌补片，并为治疗患有 CDH 的儿童提供了一种新的治疗策略。

项目成果

Evaluation of a biodegradable polyurethane patch for repair of diaphragmatic hernia in a rat model: A pilot study.

可生物降解的聚氨酯补片修复大鼠模型膈疝的评估：一项试点研究。

• 发表时间: 2023-05
• 作者: Theodorou, Christina M;Taylor, Alan;Lee, Su Yeon;Cortez, Lia Molina;Fu, Huikang;Pivetti, Christopher D;Zhang, Chaoxing;Stasyuk, Anastasiya;Hao, Dake;Kumar, Priyadarsini;Farmer, Diana L;Liao, Jun;Brown, Erin G;Hong, Yi;Wang, Aijun
• 通讯作者: Wang, Aijun