In vitro and in vivo assessments of xenogeneic cranial dura mater and naturally derived commercial dural grafts

异种颅脑硬脑膜和天然商业硬脑膜移植物的体外和体内评估

• 批准号: 10521874
• 负责人: Lakiesha Nicole Williams
• 金额: $ 38.04万
• 依托单位: UNIVERSITY OF FLORIDA
• 依托单位国家: 美国
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-09-01 至 2027-07-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10521874
• 关键词: Address; Adhesions; Antibodies; Antigen Presentation; Architecture; Biological; Brain; Cadaver; Cell Proliferation; Cell Survival; Cell-Matrix Junction; Cells; Cephalic; Cerebrospinal Fluid; Cerebrovascular Disorders; Chronic Headaches; Cicatrix; Clinic; Clinical; Collagen; Collagen Fiber; Collagen Type I; Connective Tissue; Consensus; Defect; Dura Mater; Elastic Fiber; Elastin; Electron Microscopy; Euthanasia; Evaluation; Extracellular Matrix; Extracellular Matrix Proteins; Extravasation; Failure; Family suidae; Fibroblasts; Freeze Drying; Genetic; Gold; Growth Factor; Health; Histologic; Human; Immune; Immune response; Immunologics; Implant; In Vitro; Infiltration; Inflammation; Instruction; Knowledge; Laminin; Leukocytes; Libraries; Life; Mechanics; Metabolic; Modeling; Morbidity - disease rate; Operative Surgical Procedures; PTPRC gene; Patient Selection; Patients; Performance; Perfusion; Polymers; Procedures; Process; Property; Proteins; Rattus; Research; Rodent; Role; Rupture; Secure; Site; Source; Stains; Stretching; Structure; Subdural Hematoma; Surgeon; Testing; Time; Tissues; Trauma; Tumor Cell Invasion; Tumor-infiltrating immune cells; Work; base; brain surgery; implantation; improved; in vitro Assay; in vitro Model; in vivo; infection risk; light microscopy; macrophage; mortality; neutrophil; patched protein; pre-clinical; preservation; pressure; primary outcome; repaired; replacement tissue; response; scaffold; seal; success; tissue regeneration; wound healing

Project Summary: One of dura mater’s most important functionalities is to keep Cerebral Spinal Fluid (CSF) inside of the cranial cavity. To avoid life-threatening complications there exists a need for effective and reliable dural graft replacements post-surgery. A broad selection of dura grafts exists; however, no consensus has been reached on which graft is best suited to avoid dura mater ruptures and adverse immunological responses. Naturally derived and synthetic grafts are most used as dura replacements in the clinic. Native ECM constructs, when properly treated and handled, have the potential to preserve the overall architecture of the tissue matrix. Decellularized constructs have been shown to provide structural support, adhesion sites for cell attachment, and growth factors for cell proliferation. However, the commercially available naturally derived matrices undergo extensive processing, including lyophilization, which may be cause for clearing of relevant ECM proteins needed for sustained tissue health. The research question we propose to answer in this study is Do acellular xenogeneic dural grafts elicit a less deleterious immune response than naturally derived commercial grafts and maintain structural integrity over the long term for in vivo studies? We will examine the rigor of graft sealing strength, risk of infection and/or inflammation, and wound healing/tissue incorporation in vitro and in vivo within a rat model. Our central hypothesis is that native xenogeneic ECM grafts with multiple ECM proteins will perform better than the naturally derived (commercial) ECM dural grafts due to their improved mechanical and immunological responses assayed in vitro and in vivo. This application focuses on two, multi- objective specific aims. In Aim 1 we will perform in vitro studies focused on the mechanical response, structural integrity, immunological response, and scar formation associated with four grafts. We will examine two naturally derived, commercial dural grafts, Biodesign®, and Lyoplant®, and two tissue-based grafts directly from the source—porcine dura, and cadaveric human dura. In Aim 2 we will investigate, in vivo, the border integrity of all grafts by quantifying leakage of CSF. Additionally, we will assess scar formation and immune infiltration in our xenogeneic vs. naturally derived commercially available grafts. The knowledge gained from this work will provide empirical knowledge on the role of tissue-derived xenogeneic grafts for dural replacement. Increased surgeon confidence will enable appropriate graft selection for patients, reduced operative morbidity and mortality following cranial procedures.

项目概要： 硬脑膜最重要的功能之一是保持脑脊液（CSF）在里面 颅腔的一部分为了避免危及生命的并发症，需要有效且 术后可靠的硬脑膜移植物置换。硬脑膜移植物的选择范围很广;然而， 对于哪种移植物最适合避免硬脑膜破裂， 不良免疫反应。天然来源和合成移植物最常用作硬脑膜 诊所里的替补。天然ECM构建体，当适当处理和处理时， 保持组织基质的整体结构的潜力。脱细胞构建体具有 已被证明提供结构支持、细胞附着的粘附位点和生长因子 细胞增殖的关键。然而，商业上可获得的天然衍生的基质经历了 广泛处理，包括冻干，可能导致相关ECM清除 维持组织健康所需的蛋白质。我们在本文中提出要回答的研究问题 一项研究表明，脱细胞异种硬脑膜移植物引起的免疫反应是否比 并在体内长期保持结构完整性 学业？ 我们将检查移植物密封强度的严格性，感染和/或炎症的风险， 在大鼠模型中的体外和体内伤口愈合/组织掺入。我们的核心假设 具有多种ECM蛋白的天然异种ECM移植物将比具有多种ECM蛋白的异种ECM移植物表现更好。 天然来源的（商业）ECM硬脑膜移植物由于其改善的机械和生物力学性能， 在体外和体内测定免疫应答。此应用程序侧重于两个，多- 具体目标。在目标1中，我们将进行体外研究，重点是机械 反应，结构完整性，免疫反应和疤痕形成与四个 移植物我们将研究两种天然来源的商业硬脑膜移植物Biodesign®和 Lyoplant®，以及两种直接来自猪硬脑膜和尸体的组织移植物 人类硬脑膜在目标2中，我们将在体内研究所有移植物的边界完整性， 脑脊液漏。此外，我们将评估瘢痕形成和免疫浸润， 异种移植物与天然来源的市售移植物。从中获得的知识 这项工作将提供有关组织来源的异种移植物在硬脑膜移植中作用的经验知识， 更换.增加外科医生的信心将使患者能够选择适当的移植物， 降低颅脑手术后的手术发病率和死亡率。