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

7.项目总结/摘要 过量饮酒导致疾病和增加创伤性损伤的风险 严重影响了美国的公共卫生负担。骨骼是一个重要的目标器官， 酒精的有害影响，因为它以两种不同的方式遭受酒精相关的损害;两者都直接来自 过量饮酒，间接由于酒精引起的创伤性损伤的风险增加 饮酒行为骨折不愈合是骨折损伤不能正常愈合的情况，需要 手术干预和饮酒已被证明有助于这种严重的临床风险 并发症目前，对于患有不愈合骨折的患者的临床选择，例如手术移植 自体或脱矿骨制备物各自具有严重的局限性。获取自体骨 移植物实际上是一种单独的外科手术，存在另一组并发症和脱矿骨的风险 准备工作不可靠。正常的骨折愈合是一个再生过程，利用干细胞重建 伤口处有新的骨头然而，我们目前并不了解酒精如何影响茎的活性 骨折部位的细胞我们认为，饮酒会对干细胞活性产生负面影响， 成功修复骨折。这项探索性研究的目的是检查 酒精消耗对干细胞分化潜能的影响，使用从 酒精中毒的骨科创伤患者在手术时。这将是第一 检查受伤时饮酒是否影响干细胞的能力， 治愈骨折这项研究还将研究一种潜在的机制，导致酒精抑制 干细胞分化成正常骨折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，重要的是要了解间歇性或狂欢性饮酒的影响 酗酒是青少年饮酒的普遍模式， 年轻的成年人。事实上，大约40%的骨科住院患者在 入院时间强调了理解酗酒影响的重要性 骨折修复过程中的消耗。我们认为，从这一提案中获得的数据将导致 更好地理解为什么饮酒会对骨折修复过程产生负面影响，以及我们如何 可改善骨科创伤合并骨折损伤患者的预后 通过使用有针对性的治疗方案，同时饮酒。

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.