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

基本信息

批准号：
10579321
负责人：
BRIAN T ANDREWS
金额：
$ 58.88万
依托单位：
UNIVERSITY OF OKLAHOMA
依托单位国家：
美国
项目类别：
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/10579321
关键词：
3D Print Acceleration 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 Edema 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 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 fascinate flexibility healing improved improved outcome in vivo innovation interest local drug delivery male motor deficit multidisciplinary neurological recovery neurosurgery nonhuman primate novel osteogenic particle particle exposure preservation standard of care synergism tool translational impact virtual

项目摘要

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.

项目概要该应用的长期目标是彻底改变严重创伤性脑损伤 (TBI) 的治疗通过在前所未有的单级减压中采用新型成骨水凝胶材料颅骨切除术 (DC) 是对 TBI 患者进行的一种常见的挽救生命的神经外科手术。闭合性头部损伤和/或中风时，切除颅骨可缓解颅内压升高。通过让大脑在封闭的颅骨穹窿外膨胀，患者目前正在接受手术。留下大的颅骨缺损（即头骨上有一个大洞）数周或数月，需要进行第二次手术用保留的颅骨或定制的 3D 打印材料替换缺失的颅骨。在这种情况下，第二次手术目前是不可避免的，我们的治疗策略是独特且前所未有的。 TBI 患者接受单阶段手术。我们方法的关键是一类新型水凝胶材料，其中脱矿骨的天然材料基质、失活软骨或失活肌腱本身就是我们材料的交联剂。由组织颗粒和透明质酸的糊状前体溶液组成，其行为类似于糊剂，外科医生只需照射 2 分钟的紫外线即可轻松雕刻开放性颅骨缺损区域。颗粒与透明质酸交联，形成一种坚固但柔韧的新材料，可以允许大脑最初肿胀，然后随着大脑肿胀消退而转变为骨骼。交联后的材料的特点是它可以通过释放抗炎物质来局部缓解肿胀分子来改善和加速神经恢复，此外还提供了一个保护层主要假设是我们的柔性药物洗脱水凝胶。大鼠 TBI 和 DC 后立即植入的植入物将转变为跨越颅骨的完整骨缺陷并减轻与 TBI 相关的神经功能缺损为了检验这一假设，有以下具体目标。建议：1）调整水凝胶硬度和骨再生以应用于 TBI，2）评估局部 TBI 后递送抗炎药物以减少水肿/脑损伤体积，从而改善行为恢复。我们的方法是独特的，因为我们利用肌肉骨骼再生医学作为工具来引导严重 TBI 治疗的新范例，同时也是神经外科领域治疗 TBI 的主要争论。 TBI 围绕第一次（DC）和第二次（颅骨成形术）手术之间的时间长度，我们挑战相反，我们问是否可以完全取消第二次手术。引入动态材料作为第一个也是唯一一个程序的一部分，我们有潜力做到这一点。通过前所未有的单阶段手术减轻与严重 TBI 相关的神经功能缺损。