Biodegradable Polymer Surgical Sealant with Increased Adhesion and Reduced Inflammation

可生物降解的聚合物手术密封剂，具有增强的粘附力和减少的炎症

• 批准号: 9794002
• 负责人: John Louis Daristotle
• 金额: $ 1.17万
• 依托单位: UNIV OF MARYLAND, COLLEGE PARK
• 依托单位国家: 美国
• 财政年份: 2018
• 资助国家: 美国
• 起止时间: 2018-09-21 至 2020-01-04
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9794002
• 关键词: Acute; Address; Adhesions; Adhesives; Adsorption; Anastomosis - action; Animal Model; Award; Biocompatible Materials; Biodegradation; Biological; Biology; Biomaterials Research; Body Temperature; Career Choice; Cecum; Cell Adhesion; Cell Survival; Cells; Chemistry; Clinic; Clinical; Complement; Complication; Data; Deposition; Devices; Diffuse; Diffusion; Elastomers; Ethylene Oxide; Fellowship; Fiber; Fibrin Tissue Adhesive; Fluorescence-Activated Cell Sorting; Foreign Bodies; Geometry; Glycolates; Goals; Grant; Hemostatic function; Hour; Hydration status; Hydrophobicity; Immunohistochemistry; Implant; In Vitro; Infection; Inflammation; Inflammatory; Inflammatory Response; Intestinal Motility; Intestines; Investigation; Liquid substance; Materials Testing; Methods; Modeling; Mus; National Institute of Biomedical Imaging and Bioengineering; Operating Rooms; Operative Surgical Procedures; Outcome; Particle Size; Polymers; Preparation; Procedures; Property; Proteins; Research; Safety; Scanning Electron Microscopy; Science; Site; Surface; Surgical complication; Surgical incisions; Surgical sutures; Survival Rate; Technical Expertise; Techniques; Testing; Tissue Adhesives; Tissue Engineering; Tissues; Toxic effect; Training; Translating; Water; Work; adhesive polymer; amphiphilicity; base; biodegradable polymer; biomaterial compatibility; caprolactone; copolymer; cost; design; ethylene glycol; functional group; hydrophilicity; implant material; improved; in vivo; insight; interfacial; intraperitoneal; materials science; mortality; mouse model; nanoparticle; nanoscale; particle; poly(lactide); poly(propylene oxide); portability; pre-doctoral; preclinical trial; pressure; prevent; response; scaffold; seal; small molecule; success; usability

Project Summary This project’s objective is to develop a sprayable, biodegradable polymer surgical sealant for decreasing high mortality rate complications that occur after surgery. Surgical sealants currently available in the clinic have high cost, poor material properties, and are difficult to precisely deposit. Utilizing a technique called solution blow spinning, we have demonstrated the ability to directly deposit conformal biodegradable polymer fiber surgical sealants to the site of surgery in vivo with exceptional sealing strength. The overall hypothesis for this research is that reducing inflammation and increasing tissue adhesion of polymer surgical sealants will allow us to demonstrate success in pre-clinical trials for reducing complication rate after an intestinal anastomosis. This project will investigate sprayable combinations of biodegradable polymers such as poly(lactic-co-glycolic acid) (PLGA) or poly(lactide-co-caprolactone), poly(ethylene glycol) (PEG), and functionalized nanoparticles that can reduce inflammation or increase wet tissue adhesion. The Specific Aims of the proposed research are: (1) Reduce inflammation in response to biodegradable polymers by controlling hydrophilicity using block copolymer additives. (2) Evaluate intestinal function and complication rate for PLGA-PEG surgical sealants in vivo. (3) Increase wet tissue adhesion using functionalized nanoparticles that increase physical bonding at the interface. The insights produced by these studies will also be applicable to other polymeric biomedical devices, such as sutures and tissue engineering scaffolds, increasing the significance of the work. This proposal has been designed to complement a fellowship training plan that develops cross-disciplinary technical skills in materials science and biology, leading to an academic career path in biomaterials research.

项目概要 该项目的目标是开发一种可喷涂、可生物降解的聚合物手术密封剂，以减少高风险 目前临床上可用的手术密封剂发生术后并发症的死亡率较高。 成本高，材料性能差，并且难以利用称为溶液吹塑的技术进行精确沉积。 纺丝，我们已经证明了直接沉积保形可生物降解聚合物纤维外科手术的能力 本研究的总体假设是，将密封剂应用于体内手术部位，并具有出色的密封强度。 减少炎症并增加聚合物手术密封剂的组织粘附力将使我们能够 在降低肠道吻合术后并发症发生率的临床前试验中取得了成功。 项目将研究可生物降解聚合物的可喷涂组合，例如聚（乳酸-乙醇酸） (PLGA) 或聚(丙交酯-己内酯)、聚(乙二醇) (PEG) 和功能化纳米粒子，可以 减少炎症或增加湿组织粘附。拟议研究的具体目标是：（1） 通过使用嵌段共聚物控制亲水性来减少生物可降解聚合物引起的炎症 (2) 评估 PLGA-PEG 手术密封剂的体内肠道功能和并发症发生率。 使用功能化纳米颗粒增加湿组织粘附力，增加界面处的物理结合。 这些研究产生的见解也适用于其他聚合物生物医学设备，例如 缝合线和组织工程支架，增加了这项工作的意义。 旨在补充奖学金培训计划，培养材料方面的跨学科技术技能 科学和生物学，通向生物材料研究的学术职业道路。