Single stage surgical intervention for treatment of severe traumatic brain injury - DIVERSITY SUPPLEMENT

用于治疗严重创伤性脑损伤的单阶段手术干预 - 多样性补充

• 批准号: 10622749
• 负责人: BRIAN T ANDREWS
• 金额: $ 6.65万
• 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: 2022-06-01 至 2026-02-28
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10622749
• 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; 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; 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; 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; parent grant; particle; particle exposure; preservation; standard of care; synergism; tool; translational impact; virtual

PROJECT SUMMARY [PARENT R01NS123051] 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[父R01NS123051] 这是革新严重脑损伤治疗的长期目标 （TBI）通过在未经预科的单阶段中采用新型的成骨水凝胶材料 Decompressive craniew（DC）程序。 对于闭合头部损伤和/或中风的TBI患者。 颅内通过允许大脑在闭合的钙毛上肿胀 程序，患者目前处于较大的颅骨缺陷（即头骨上的大孔）数周或 月份，需要进行第二手术，以用保留的颅骨或A代替缺失的颅骨 定制的3D模式 通过单阶段手术治疗TBI患者，独特且前所未有。 我们方法的关键是一种新的水凝胶材料，是脱矿的天然材料 骨基质，退化软骨或退化肌腱是水凝胶的交联。 材料由组织颗粒和透明质酸的糊状前体溶液组成，其表现为 粘贴外科医生可以轻松地雕刻到开放的钙钙缺陷区域。 暴露于颗粒与透明质额帐户交联，以创建一种固体的新材料 柔性，并且可以使大脑最初肿胀，并且随着大脑肿胀的过渡到骨骼 取消交联后的材料创新 释放抗炎分子肿胀以改善和加速神经内聚物的恢复，并 此外，在头皮和人体最不可或缺的器官之间提供了保护层。 假设是，我们在TBI和DC中立即放置的柔性，洗脱的水凝胶植入物在大鼠中 将过渡到完整的骨骨，跨越颅骨缺陷，并减轻与与之相关的神经病缺陷。 TBI。要检验此假设，以下特定目的是支撑的：1） 在TBI中申请的再生和2）评估TBI之后的局部抗炎药物递送 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的再生医学作为一种工具来吸引 在新的TBI治疗的新范式中。 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 是否有必要进行辩论。 通过引入动态材料作为第一个的一部分，只有印刷。 减轻与严重TBI相关的神经功能缺陷的潜力 程序。