Single stage surgical intervention for treatment of severe traumatic brain injury

一期外科手术治疗严重创伤性脑损伤

• 批准号: 10444708
• 负责人: BRIAN T ANDREWS
• 金额: $ 64.16万
• 依托单位: UNIVERSITY OF OKLAHOMA
• 依托单位国家: 美国
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-03-01 至 2026-02-28
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10444708
• 关键词: 3D Print; Address; Animals; Anti-Inflammatory Agents; Anxiety; Area; Behavior; Behavioral; Biocompatible Materials; Biomedical Engineering; Bone Matrix; Bone Regeneration; Brain; Brain Edema; Brain Injuries; Calvaria; Caring; Cartilage; Cause of Death; Cephalic; Cessation of life; Clinic; Clinical Trials; Closed head injuries; Cognitive; Complication; Control Groups; Crosslinker; Custom; Data; Defect; Drug Delivery Systems; Emergency department visit; Encephalitis; Evaluation; Female; Formulation; Goals; Headache; Histology; Hospitalization; Hyaluronic Acid; Hydrogels; Implant; In Vitro; Industry; Intracranial Pressure; Left; Letters; Life; Magnetic Resonance Imaging; Medical; Mental Depression; Modeling; Modernization; Motor; Mus; Musculoskeletal; Neurologic; Neurologic Deficit; Neurosurgical Procedures; Operative Surgical Procedures; Organ; Osteoblasts; Paste substance; Patients; Pharmaceutical Preparations; Pliability; Procedures; Process; Property; Rattus; Recovery; Regenerative Medicine; Resolution; Rheology; Savings; Scalp structure; Solid; Speed; Stroke; Surgeon; Survivors; Swelling; Symptoms; TBI Patients; TBI treatment; Tendon structure; Testing; Thinness; Time; Tissues; Traumatic Brain Injury; Ultraviolet Rays; United States; animal model selection; base; biomaterial development; bioprinting; bone; bone repair; craniofacial bone; cranium; cranium plastic repair; crosslink; demineralization; design; disability; experience; flexibility; healing; improved; improved outcome; in vivo; innovation; interest; local drug delivery; male; mild traumatic brain injury; motor deficit; multidisciplinary; neurological recovery; neurosurgery; nonhuman primate; novel; osteogenic; particle; particle exposure; preservation; standard of care; synergism; tool; translational impact; virtual

PROJECT SUMMARY The long-term objective of this application is to revolutionize the treatment of severe traumatic brain injury (TBI) by employing a novel osteogenic hydrogel material in an unprecedented single-stage decompressive craniectomy (DC) procedure. DC is a common life-saving neurosurgical procedure performed on TBI patients with either closed head injury and/or stroke. Removing the cranial bone mitigates rising intracranial pressures by allowing the brain to swell outside the closed calvarial vault. Following the procedure, patients are currently left with a large cranial defect (i.e., a large hole in their skull) for weeks or months and require a 2nd surgery to replace the missing cranial bone with their preserved cranial bone or a custom 3D-printed material. In such cases, this 2nd surgical procedure is currently unavoidable. Our strategy is unique and unprecedented by treating TBI patients with a single-stage surgical procedure. The key to our approach is a new class of hydrogel materials, where natural materials of demineralized bone matrix, devitalized cartilage, or devitalized tendon are themselves the crosslinkers of the hydrogel. Our material consists of a paste-like precursor solution of tissue particles and hyaluronic acid that behaves as a paste that a surgeon can easily sculpt into the open calvarial defect area. With only 2 minutes of UV light exposure the particles are crosslinked with the hyaluronic acid to create a new material that is solid, yet flexible, and can allow the brain to swell initially, and then transition into bone as the brain swelling subsides. The innovation of this material after crosslinking is that it can provide localized relief of swelling by releasing anti-inflammatory molecules to improve and accelerate neurological recovery, and moreover provide a protective layer between the scalp and the body’s most indispensable organ. The chief hypothesis is that our flexible, drug-eluting hydrogel implants placed immediately following TBI and DC in rats will transition to complete bone spanning the cranial defect and mitigate neurologic deficits associated with TBI. To test this hypothesis, the following Specific Aims are proposed: 1) Tune hydrogel stiffness and bone regeneration for application to TBI, and 2) Evaluate localized anti-inflammatory drug delivery after TBI to reduce edema/brain injury volume and thereby to improve behavioral recovery. Our approach is unique in that we are leveraging musculoskeletal regenerative medicine as a tool to usher in a new paradigm for severe TBI treatment. While a primary debate in the neurosurgery field for treatment of TBI revolves around the amount of time between the 1st (DC) and 2nd (cranioplasty) procedures, we challenge whether that debate is even necessary. Instead, we ask whether the 2nd surgery can be eliminated altogether by introducing a dynamic material as part of the first, and only procedure. In so doing, we hold the potential to mitigate neurologic deficits associated with severe TBI with an unprecedented single-stage procedure.

项目摘要 该应用的长期目的是彻底改变严重的脑损伤治疗（TBI） 通过在前所未有的单阶段减压中使用新型的成骨氢材料 颅骨切开术（DC）程序。 DC是对TBI患者进行的常见挽救生命的神经外科手术 闭合头部受伤和/或中风。去除颅骨减轻颅内压力升高 通过允许大脑在闭合的颅关穹顶外肿胀。遵循该程序，患者目前是 留下较大的颅骨缺陷（即头骨上的大孔）数周或数月，需要进行第二手术才能 用保存的颅骨或定制的3D打印材料代替缺失的颅骨。在这样 病例，目前不可避免地，这第二次手术程序是不可避免的。我们的策略是独特的，并且通过治疗前所未有 具有单级手术手术的TBI患者。 我们方法的关键是一种新的水凝胶材料，债务的天然材料 基质，退化软骨或退化肌腱本身就是水凝胶的交联。我们的材料 由组织颗粒和氢气酸的糊状前体溶液组成，其表现为糊状物 外科医生可以轻松地雕刻到开放的颅骨缺陷区域。只有2分钟的紫外线暴露 颗粒与透明质酸交联，以创建一种固体但柔性的新材料，并且可以允许 大脑最初会肿胀，然后随着大脑肿胀消退而过渡到骨头。这个创新 交联后的材料是，它可以通过释放抗炎作用提供局部浮肿 分子改善和加速神经系统恢复，此外， 头皮和人体最必不可少的器官。主要的假设是我们的柔性，洗脱水凝胶 TBI和DC在大鼠中立即放置的植入物将过渡到跨越颅骨的骨骼 缺陷和减轻神经系统定义与TBI相关。为了检验这一假设，以下特定目标 提出：1）调整水凝胶刚度和骨再生以应用于TBI，2）评估本地化 TBI后的抗炎药物输送以减少水肿/脑损伤量，从而改善行为 恢复。 我们的方法是独一无二的，因为我们利用肌肉骨骼再生医学作为迎接工具 在新的严重TBI治疗范式中。而神经外科领域的主要辩论 TBI围绕着第1（DC）和第二个（颅骨成形术）程序之间的时间旋转，我们挑战 该辩论是否必要。相反，我们询问是否可以通过 引入动态材料作为第一个也是唯一过程的一部分。这样做，我们有潜力 减轻神经系统定义了与史无前例的单阶段程序相关的严重TBI。