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

• 批准号: 10474458
• 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
• 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/10474458
• 关键词: 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; Deposition; Development; 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

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.

项目总结