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

基本信息

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
项目类别：
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

项目摘要

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留脑脊液 (CSF) 为了避免危及生命的并发症，需要有效和可靠的方法。可靠的术后硬脑膜移植物替代品存在多种硬脑膜移植物；对于哪种移植物最适合避免硬脑膜破裂尚未达成共识不良免疫反应最常用作硬脑膜。诊所中的原生 ECM 结构如果经过适当的处理和处理，具有以下特点：具有保留组织基质整体结构的潜力。已被证明可以提供结构支撑、细胞附着的粘附位点和生长因子然而，商业上可获得的天然衍生基质会经历细胞增殖。广泛的加工，包括冻干，这可能会导致相关 ECM 的清除我们建议在此回答的研究问题是维持组织健康所需的蛋白质。研究是非细胞异种硬脑膜移植物引起的有害免疫反应是否比天然衍生的商业移植物并在体内长期保持结构完整性学习？我们将检查移植物密封强度的强度、感染和/或炎症的风险，以及我们的中心假设是在大鼠模型中体外和体内伤口愈合/组织合并。具有多种 ECM 蛋白的天然异种 ECM 移植物的性能优于自然衍生的（商业）ECM 硬脑膜移植物由于其改进的机械和体外和体内测定的免疫反应本应用集中于两种、多种。在目标 1 中，我们将进行侧重于机械性能的体外研究。反应、结构完整性、免疫反应和与四种相关的疤痕形成我们将检查两种天然衍生的商业硬脑膜移植物 Biodesign® 和 Lyoplant®，以及两种直接来自来源的组织移植物——猪硬脑膜和尸体在目标 2 中，我们将通过定量研究体内所有移植物的边界完整性。此外，我们将评估我们的疤痕形成和免疫浸润。异种与自然衍生的商业移植物从中获得的知识。这项工作将为硬脑膜组织来源的异种移植物的作用提供经验知识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。