Resorbable, Phsophorylated Poly(ester urea) Surgical Adhesive to Enhance Fracture Healing

可吸收的磷酸化聚（酯脲）手术粘合剂可促进骨折愈合

基本信息

批准号：
10674973
负责人：
Joseph S. Fernandez-Moure
金额：
$ 16.69万
依托单位：
DUKE UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
2021
资助国家：
美国
起止时间：
2021-09-01 至 2026-08-31
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/10674973
关键词：
Acceleration Actins Adhesions Adhesives Amino Acids Award Biocompatible Materials Biologic Characteristic Biomechanics Biomedical Engineering Bone Marrow Bone Marrow Stem Cell Bone callus Breathing Calcium Cartilage Cells Chemicals Chest wall structure Chondrocytes Clinical Collagen Contracts Critical Care Cues Cytoskeletal Modeling Data Dedications Deposition Development Elasticity Elastomers Engineering Esters Ethanol Exhibits External Fixation Devices Failure Flail Chest Focal Adhesions Formulation Foundations Fracture Future Generations Glycols Goals Immobilization In Vitro Incidence Injectable Injections Injury Investigation Laboratory Research Life Mechanics Mentors Metabolic Modeling Modification Modulus Musculoskeletal Operative Surgical Procedures Orthopedics Osteoblasts Pain Patients Performance Phosphorylation Phosphoserine Play Pneumonia Polymers Positioning Attribute Program Development Property Public Health Rattus Research Research Personnel Rib Fractures Scientist Stem Cell Research Stromal Cells Surface Surgeon Tensile Strength Testing Tissue Engineering Trauma Trauma patient Traumatic injury United States United States National Institutes of Health Universities Urea Vertebral column Work acute care base biodegradable polymer bone bone fracture repair bone healing career career development clinical practice copolymer cortical bone density elastomeric experience experimental study healing high risk improved in vivo innovation inorganic phosphate insight interfacial long bone materials science mechanical properties mechanical signal minimally invasive monomer novel novel therapeutics polymerization professor pulmonary function reparative process rib bone structure safety testing skills stoichiometry surgery material trauma care treatment strategy wound healing

项目摘要

PROJECT SUMMARY This proposal presents a five-year research career development program focused on optimizing the physical and biological characteristics of phosphorylated poly(ester ureas) (pPEU) for the stabilization and healing of rib fractures. The candidate is currently an Assistant Professor of Surgery and acute and critical care trauma surgeon at Duke University, with previous research experience in biologic materials and tissue engineering research. He has now chosen to focus on materials science and mechanical engineering with a diverse mentoring committee of investigators with expertise in materials, polymers, musculoskeletal reparative processes and stem cell research. The proposed experiments and didactic work will provide the candidate with a unique set of skills that will help him transition to independence as a surgeon-scientist and enable him to fill a significant “experience gap” in the field of research dedicated to rib fractures and wound healing. Rib fractures account for nearly 40% of all bone fractures sustained in the each year, with over a quarter million rib injuries. These injuries can have long-lasting effects, sometimes even for life. Over half of rib fracture patients contract pneumonia, and nearly two thirds will still experience significant pain in the chest wall years after sustaining the injury. While stabilization of a fracture promotes faster healing and decreased rates of non-union (failure of a broken bone to heal), rib fractures present a unique challenge in that immobilization can only be accomplished through invasive surgical intervention. Therefore, unlike long bone fractures where immediate stabilization is standard, this is reserved in rib fractures for only the most severe cases. Poly(ester ureas) (PEU) are amino acid based biodegradable polymers with bone like mechanical properties. One such phosphorylated PEU (pPEU) copolymer, based on phosphoserine (pSer) is ethanol soluble allowing for injection, with strong bone adhesion and high elastic moduli, making pPEU’s ideal as an innovative, non-invasive solution for the stabilization of rib fractures. However, the effect of pSer stoichiometry on PEU copolymer osteoinduction remains unknown, as well as if a provisional elastomeric callus using resorbable PEU based adhesive can accelerate bone healing through early fracture stabilization. This proposal will determine the relationships between the physical and biologic characteristics of injectable pSer-PEU for osteoinduction and test the safety and performance of pSer-PEU in a rat model of rib fracture. The work of this proposal will 1) characterize the relationship of pSer stoichiometry within the PEU copolymers on biomechanics (tensile strength, elastic modulus, and stiffness), and interfascial adhesion of pSer-PEU; 2) quantify bone marrow stromal cell (BMSC) cytoskeletal reorganization and osteoinduction to increased stiffness, and 3) evaluate fracture stability and callus formation in a rat rib fracture model with best performing pSer-PEU. The results of this work will serve as the basis for future projects focused on using functionalized biomaterials to understand the cellular mechanisms of fracture healing in order to optimize healing in the high risk trauma patient.

项目概要该提案提出了一个为期五年的研究职业发展计划，重点是优化身体素质磷酸化聚酯脲（pPEU）用于肋骨稳定和愈合的生物学特性该候选人目前是外科和急性和重症护理创伤的助理教授。杜克大学外科医生，拥有生物材料和组织工程研究经验他现在选择专注于材料科学和机械工程的多元化研究。由具有材料、聚合物、肌肉骨骼修复专业知识的研究人员组成的指导委员会拟议的实验和教学工作将为候选人提供过程和干细胞研究。一套独特的技能将帮助他过渡到作为一名外科医生科学家的独立地位，并使他能够填补在肋骨骨折和伤口愈合的研究领域存在显着的“经验差距”。肋骨骨折占每年所有骨折的近 40%，超过 25 万例肋骨损伤。这些损伤可能会产生长期影响，有时甚至对一半以上的肋骨骨折患者造成终生影响。感染肺炎，数年后近三分之二的胸壁仍会感到剧烈疼痛维持骨折的稳定性可促进更快的愈合并降低不愈合率。（断骨无法愈合），肋骨骨折带来了独特的挑战，因为只能通过固定来固定因此，与长骨骨折不同，它是通过侵入性手术干预来完成的。稳定是标准配置，仅在最严重的情况下保留肋骨骨折。是一种基于氨基酸的生物可降解聚合物，具有类似骨的机械性能。基于磷酸丝氨酸 (pSer) 的 PEU (pPEU) 共聚物可溶于乙醇，可注射，具有强效骨粘附力和高弹性模量，使 pPEU 成为理想的创新、非侵入性解决方案然而，pSer 化学计量对 PEU 共聚物骨诱导的影响仍然存在。未知，以及使用可吸收 PEU 粘合剂的临时弹性愈伤组织是否可以加速通过早期骨折稳定来实现骨愈合。该提案将确定骨折之间的关系。用于骨诱导的可注射 pSer-PEU 的物理和生物学特性并测试其安全性和 pSer-PEU 在肋骨骨折大鼠模型中的性能本提案的工作将 1) 表征 PEU 共聚物内 pSer 化学计量与生物力学（拉伸强度、弹性模量、和硬度），以及 pSer-PEU 的筋膜间粘附力 2）量化骨髓基质细胞 (BMSC) 细胞骨架；重组和骨诱导以增加刚度，3) 评估骨折稳定性和愈伤组织形成在具有最佳性能的 pSer-PEU 的大鼠肋骨骨折模型中，这项工作的结果将作为未来的项目侧重于使用功能化生物材料来了解骨折的细胞机制愈合以优化高风险创伤患者的愈合。