Development of a Polysaccharide-Based Patch for Use as a Therapeutic Lung Sealant

开发用作治疗性肺封闭剂的多糖贴剂

基本信息

批准号：
9353423
负责人：
Rachael Floreani
金额：
$ 38.64万
依托单位：
UNIVERSITY OF VERMONT & ST AGRIC COLLEGE
依托单位国家：
美国
项目类别：
财政年份：
2016
资助国家：
美国
起止时间：
2016-09-15 至 2020-06-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/9353423
关键词：
Address Adherence Adhesions Adhesives Affect Air Alginates Chemicals Chest Chest Tubes Chronic Development Disease Drug Carriers Drug Controls Elasticity Encapsulated Ensure Experimental Designs FGF2 gene Formulation Glues Goals Growth Factor Health Care Costs Hyaluronan Hydrogels Infection Inflammation Injury Lead Length of Stay Life Liquid substance Longevity Lung Lung Volume Measurements Lung diseases Maintenance Malignant Neoplasms Mechanics Medical Methacrylates Microspheres Modeling Modification Molecular Weight Morbidity - disease rate Mus Nature Operative Surgical Procedures Oxides Pharmaceutical Preparations Pleura Pleural Pleurodesis Polymers Polysaccharides Prevention Procedures Property Rattus Reaction Research Rodent Rodent Model Scheme Structure of parenchyma of lung Surface Techniques Therapeutic Therapeutic Agents Therapeutic Uses Time Tissues Trauma United States Visible Radiation Wound Healing base clinical efficacy cohesion controlled release crosslink flexibility healing histological image improved in vivo lung volume mechanical properties mortality oxidation physical property pre-clinical pressure public health relevance rate of change repaired seal tissue regeneration wound

项目摘要

DESCRIPTION: Lung leaks from surgery, injury or diseases may result in lung collapse, which can be immediately life threatening. Treating a collapsed lung begins with emergent placement of a chest tube into the pleural space so that the accumulated air or liquid can be evacuated in order to re-inflate the lung. However, collapse often occurs in the setting of poorly healing tissue. Extensive tissue damage and chronic leak lead to substantial morbidity, mortality, and correspondingly high health care costs. To address these challenges, the proposed research will explore the use of a natural material, alginate, for use as a tissue sealant and therapeutic patch, to effectively treat lung leaks and aid in lung tissue regeneration. Chemically modified alginate, methacrylated alginate (Alg-MA), will be further modified to enhance adhesion to the lung surface to form a better seal. The use of the hydrogel as a drug carrier is also proposed to enhance wound healing. The overarching goal of our application is thus to establish the potential clinical efficacy of Alg- MA hydrogels as combination pleural sealants and therapeutic patches. The experimental design is centered on three aims: 1) to determine how the physical properties of Alg-MA hydrogels impact their capacity to seal a pleural leak, 2) to determine how Alg-MA hydrogel properties affect their capacity for dynamic mechanical stability and controlled release of drugs, and 3) to assess the ability of drug-eluting Alg-MA hydrogels to repair damaged pleural tissue in vivo. Alg-MA materials will be oxidized to enhance tissue adhesion, thus improving the burst pressure and sealant properties of the material. In addition, blending of Alg-MA with a similar natural material, hyaluronan (HA) will enhance the dynamic mechanical properties to ensure dynamic durability and longevity of leak prevention in vivo. To characterize the long-term use of the hydrogel sealant, adhesion and mechanical properties will be tailored to enhance degradation properties and drug release rates. An in vivo rodent model will be used to evaluate the efficacy of Alg-MA hydrogels as durable sealants and carriers for therapeutic drugs. Indeed, the broader impact of the proposed research is the development of a medical sealant for various uses, especially in cases when selective tissue adhesion is desired.

描述：手术、受伤或疾病引起的肺漏可能会导致肺部塌陷，这可能会立即危及生命。治疗塌陷的肺部首先需要将胸管紧急插入胸膜腔，以便将积聚的空气或液体排出。然而，在组织愈合不良和慢性渗漏的情况下，经常会发生塌陷，从而导致大量的发病率、死亡率和相应的高医疗费用。拟议的研究将探索使用天然材料海藻酸盐作为组织密封剂和治疗贴片，以有效治疗肺渗漏并帮助肺组织再生。还建议使用水凝胶作为药物载体来增强与肺表面的粘附力，以增强伤口愈合。 Alg-MA 水凝胶作为胸膜密封剂和治疗贴片的组合实验设计集中于三个目标：1) 确定 Alg-MA 水凝胶的物理特性如何影响其密封胸膜渗漏的能力，2) 确定 Alg-MA 水凝胶如何影响其密封胸膜渗漏的能力。 MA水凝胶的特性影响其动态机械稳定性和药物控制释放的能力，并且3)评估药物洗脱Alg-MA水凝胶在体内修复受损胸膜组织的能力。氧化以增强组织粘附力，从而提高材料的爆破压力和密封性能。此外，Alg-MA 与类似天然材料透明质酸 (HA) 的混合将增强动态机械性能，以确保动态耐久性和泄漏寿命。为了表征水凝胶密封剂的长期使用，将定制粘附性和机械性能以增强降解性能和药物释放率，将使用体内啮齿动物模型来评估 Alg-MA 的功效。事实上，该研究的更广泛影响是开发用于各种用途的医用密封剂，特别是在需要选择性组织粘附的情况下。