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: 10417883
• 负责人: JOHN J. CALLACI
• 金额: $ 22.14万
• 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 2024-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10417883
• 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; 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; Lead; Life; Mesenchymal Stem Cells; Minerals; Molecular; Morbidity - disease rate; Operative Surgical Procedures; Organ; Orthopedics; Osteoblasts; Osteogenesis; Pathway interactions; Patients; Pattern; Persons; Pharmacology; Physiologic Ossification; Play; Population; Preparation; Process; Prognosis; Proliferating; Proteins; Public Health; Regimen; Research; Risk; Risk Factors; Rodent; Rodent Model; Role; Sampling; Signal Transduction; Site; Skeleton; Smoking; Steroids; Therapeutic; Time; Trauma patient; Traumatic injury; United States; Work; alcohol effect; alcohol exposure; base; beta catenin; binge drinking; biological adaptation to stress; bone; bone fracture repair; cartilaginous; cell type; clinical effect; clinically relevant; drinking behavior; epidemiology study; experimental study; healing; high risk; improved; in vitro Model; in vivo; injured; mortality; negative affect; novel; osteoblast differentiation; osteogenic; problem drinker; regenerative; skeletal injury; sobriety; stem cell differentiation; 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。项目摘要/摘要 过度饮酒导致疾病并增加创伤性损伤的风险 在美国的公共卫生负担很大。骨骼是一个重要的目标器官 酒精的有害影响是因为它以两种不同的方式遭受了与酒精有关的损害。都直接来自 过度饮酒，间接由于酒精造成的创伤性损伤风险增加 饮酒行为。骨折骨不连的是骨断裂损伤正常愈合的条件 手术干预和饮酒已被证明会导致这种严重临床的风险 并发症。当前，针对非愈合骨折患者的临床选择，例如手术移植 自源或去矿物化的骨骼制剂都有严重的局限性。获得自体骨 移植物实际上是一种单独的外科手术程序，面临另一组并发症和去矿物化骨的风险 准备工作是不可靠的。正常骨折愈合是一种再生过程，利用干细胞重建 受伤部位的新骨。但是，我们目前不了解酒精如何影响茎的活性 骨折部位的细胞。我们认为，饮酒会对干细胞活动产生负面影响，这是至关重要的 成功的断裂修复。这项探索性研究的目的是检查 使用从干细胞分化潜力的饮酒，使用从 在手术时，酒精感染的骨科创伤患者。这将是第一个 检查受伤时的饮酒是否会影响干细胞的能力 治愈骨折。该研究还将检查导致酒精抑制的潜在机制 干细胞从分化为正常断裂修复所需的细胞类型。因为年轻人 更有可能遭受创伤性伤害，重要的是要了解情节或暴饮暴食的影响 在裂缝维修中，由于饮酒是在两种青少年中饮酒的普遍模式 和年轻的成年人。大约40％的骨科住院群体陶醉的事实 住院时间强调了理解暴饮暴食的影响的重要性 裂缝维修过程中的消费。我们认为，从该提案中获得的数据将导致 更好地理解为什么饮酒会对破裂维修过程产生负面影响以及我们如何 可以改善骨折骨折骨折造成骨折的预后 伴随饮酒，尽管使用有针对性的治疗方案。