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.

项目总结

项目成果

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

• DOI: 10.1016/j.jpedsurg.2023.01.036
• 发表时间: 2023-05
• 期刊: JOURNAL OF PEDIATRIC SURGERY
• 影响因子: 2.4
• 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