Effects of Acute and Chronic Alcohol Intoxication on Fracture Healing in Orthopaedic Trauma Patients: Effects on Mesenchymal Stem Cell Lineage Differentiation Required for Fracture Repair

急性和慢性酒精中毒对骨科创伤患者骨折愈合的影响：对骨折修复所需的间充质干细胞谱系分化的影响

• 批准号: 10646469
• 负责人: JOHN J. CALLACI
• 金额: $ 18.29万
• 依托单位: LOYOLA UNIVERSITY CHICAGO
• 依托单位国家: 美国
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-06-20 至 2025-05-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10646469
• 关键词: Accidents; Acute; Adolescent and Young Adult; Affect; Alcohol abuse; Alcohol consumption; Alcoholic Intoxication; Alcohols; Area; Beverages; Biological Models; Bone Marrow; Bone Transplantation; Bone callus; Bone necrosis; Caring; Cell Lineage; Cell Separation; Chondrocytes; Chronic; Clinical; Complication; Country; Data; Diabetes Mellitus; Differentiation Antigens; Disease; FOXO1A gene; Fracture; Goals; Heavy Drinking; Histone Deacetylase; Hospitalization; Impairment; Injury; Inpatients; Intervention; Intoxication; Investigation; Laboratories; Life; Mesenchymal Stem Cells; Molecular; Morbidity - disease rate; Operative Surgical Procedures; Organ; Orthopedics; Osteoblasts; Osteogenesis; Pathway interactions; Patients; Pattern; Persons; Physiologic Ossification; Play; Population; Preparation; Process; Productivity; Prognosis; Proteins; Public Health; Regimen; Research; Risk; Risk Factors; Rodent; Rodent Model; Role; Sampling; Signal Transduction; Sirtuins; Site; Skeleton; Smoking; Steroids; Therapeutic; Time; Trauma patient; Traumatic injury; United States; Work; alcohol effect; alcohol exposure; beta catenin; binge drinking; biological adaptation to stress; bone; bone fracture repair; cartilaginous; cell type; clinical effect; clinically relevant; demineralization; drinking behavior; epidemiology study; experimental study; healing; high risk; improved; in vitro Model; in vivo; injured; mortality; negative affect; novel; osteoblast differentiation; osteogenic; pharmacologic; problem drinker; regenerative; skeletal injury; sobriety; stem cell differentiation; stem cell proliferation; stem cells; targeted treatment; treatment strategy

7. PROJECT SUMMARY/ABSTRACT Excessive alcohol consumption resulting in disease and increasing the risk of traumatic injury contributes significantly to the public health burden in the United States. The skeleton is a significant target organ for the deleterious effects of alcohol because it suffers alcohol-related damage in two distinct ways; both directly from excessive alcohol consumption, and indirectly due to the increased risk for traumatic injury caused by alcohol drinking behavior. Fracture nonunion is a condition where a bone fracture injury fails to heal normally requiring surgical intervention and alcohol consumption has been shown to contribute to the risk for this serious clinical complication. Currently, clinical options for patients with a non-healing fracture such as surgical grafting of autogenous or de-mineralized bone preparations each have serious limitations. Obtaining autogenous bone graft is effectively a separate surgical procedure at risk for another set complications and de-mineralized bone preparations are unreliable. Normal fracture healing is a regenerative process that utilizes stem cells to rebuild new bone at the injury site. However, we currently do not understand how alcohol affects the activity of stem cells at the fracture site. We believe that alcohol consumption negatively affects stem cell activity that is critical to successful fracture repair. The goal of this exploratory investigation is to examine the effects of alcohol consumption on stem cell differentiation potential, using clinical samples obtained from alcohol-intoxicated orthopaedic trauma patients at the time of surgery. This will be the first examination of whether alcohol consumption at the time of injury affects the ability of stem cells to heal a bone fracture. The study will also examine a potential mechanism that causes alcohol to inhibit stem cells from differentiating into cell types required for normal fracture repair. Because young people are more likely to suffer traumatic injury, it is important to understand the effects of episodic or binge drinking on fracture repair as binge alcohol consumption is the prevalent pattern of alcohol drinking in both adolescent and young adult populations. The fact that about 40% of the orthopaedic inpatient population is intoxicated at the time of hospital admission underscores the significance of understanding the impact of binge alcohol consumption on the fracture repair process. We believe that the data obtained from this proposal will lead to a better understanding of why alcohol consumption negatively impacts the fracture repair process and how we can improve the prognosis for orthopaedic trauma patients with bone fracture injuries complicated by concomitant alcohol consumption though the use of targeted therapeutic regimens.

7. 项目总结/文摘