"A Two-Stage High-Fidelity, Anti-Infective Approach to Craniofacial Repair in Novel Ovine Model"

“新型绵羊模型中的两阶段高保真、抗感染颅面修复方法”

• 批准号: 9469020
• 负责人: Emma Watson
• 金额: $ 4.48万
• 依托单位: RICE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2017
• 资助国家: 美国
• 起止时间: 2017-08-17 至 2020-08-16
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9469020
• 关键词: 3D Print; Address; Affect; Animal Model; Animal Testing; Animals; Anti-Infective Agents; Antibiotic Resistance; Antibiotics; Autologous Transplantation; Bacteria; Bacterial Infections; Biocompatible Materials; Biomedical Engineering; Bioreactors; Blood; Bone Growth; Bone Regeneration; Bone Tissue; Bone Transplantation; Ceramics; Clinical; Communication; Complex; Congenital Abnormality; Craniofacial Abnormalities; Custom; Defect; Development; Dimensions; Disease; Distal; Distant; Ensure; Esthetics; Evaluation; Excision; Fellowship; Focal Infection; Geometry; Goals; Growth; Harvest; Heart Rate; High Pressure Liquid Chromatography; Histology; Hydroxyapatites; Immune response; Implant; Incidence; Infection; Inflammation; Investigation; Kinetics; Knowledge; Lead; Literature; Maintenance; Mandible; Mechanics; Methods; Minimum Inhibitory Concentration measurement; Modeling; Molds; Monitor; Morbidity - disease rate; Mucous Membrane; Oral; Oral cavity; Organ Transplantation; Outcome; Patients; Periosteum; Pharmaceutical Preparations; Polymerase Chain Reaction; Polymers; Polymethyl Methacrylate; Porosity; Property; Publishing; Repair Complex; Research; Shapes; Sinus; Site; Skin; Specific qualifier value; Surgeon; Swab; System; Temperature; Testing; Therapeutic; Thinness; Time; Tissue Donors; Tissue Engineering; Tissues; Trauma; Validation; Work; base; bone; bone engineering; cell type; combat; commercialization; craniofacial; craniofacial complex; craniofacial repair; cytokine; design; healing; implantation; improved; in vivo; inflammatory marker; long bone; maxillofacial; mechanical properties; member; novel; novel strategies; reconstruction; repaired; response; rib bone structure; scaffold; soft tissue; tissue repair; tomography; tool; tumor

Project Summary/Abstract The rationale for this project is based on the need for improved strategies for functional and aesthetic reconstruction of craniofacial defects caused by trauma, tumor removal, infection, congenital malformations, or other diseases. Due to many tissue types in close proximity and a nearby bacteria-filled oral cavity, repair of craniofacial tissue is complex. Therefore, the objective of this study is to develop novel approaches and to improve upon existing strategies for craniofacial bone tissue repair by utilizing a scaffold to promote soft tissue healing and space maintenance of the defect, local antibiotic release to combat infection, and tissue growth of specified geometry at a distant site within the body to eliminate donor-site morbidity associated with autograft for repair. The proposed research will test the fundamental hypothesis that local release of antibiotics will eliminate local infection, restore soft tissue healing at the defect site, and allow robust bone growth at a distal site. The proposed research will be accomplished through two specific aims: 1) To manufacture and characterize properties of space maintainers utilizing different antibiotic-loading methods to understand kinetics of antibiotic release and to ensure mechanical properties are adequate for mandibular implantation and 2) To evaluate the effects of an antibiotic-releasing space maintainer on mandibular infection in an in vivo large animal model while bone is grown adjacent to rib periosteum in a 3D printed bioreactor. The space maintainers will be evaluated via mechanical testing (compression, 4-point bending, screw pull-out) and microcomputed tomography (microCT) (for pore size and porosity). The released antibiotic concentration will be evaluated via high performance liquid chromatography (HPLC). Bacteria will be utilized to determine minimum inhibitory concentration of antibiotic. In order to evaluate the effects of the space maintainer in vivo, the mandibular site will be swabbed (for identification, testing of potential antibiotic resistance) and will be analyzed by microCT for bone growth and histology for tissue and cell types. The tissue grown in bioreactors will be analyzed by microCT and by histology for bone growth, with quantitative polymerase chain reaction (qPCR), and via compression and screw pull-out testing. Blood drawn at several time points will be utilized to detect systemic markers of infection, oral swabs will be cultured, and vitals (such as heart rate and temperature) will be monitored. Upon completion of these studies, the expected outcomes are the successful fabrication of a space maintainer capable of antibiotic release with robust mechanical properties, the successful utilization of 3D printed bioreactors in a large animal model, and the successful development of a large animal model with sustained, yet localized, mandibular infection. In addition to improving upon existing strategies, this work will broaden our understanding on the interplay between bacteria, immune response, antibiotic delivery, and bone growth. Moreover, the proposed system provides a therapeutic approach for complex defects of large or unusual sizes that cannot utilize traditional autograft tissues due to shape or size constraints.

项目概要/摘要 该项目的基本原理是基于改进功能和美学策略的需要 因创伤、肿瘤切除、感染、先天畸形或其他原因引起的颅面缺损的重建 其他疾病。由于许多组织类型非常接近并且附近充满细菌的口腔，修复 颅面组织很复杂。因此，本研究的目的是开发新方法并 通过利用支架促进软组织来改进颅面骨组织修复的现有策略 缺损的愈合和空间维持、局部抗生素释放以对抗感染以及组织生长 在体内远处部位指定几何形状，以消除与自体移植相关的供体部位发病率 维修。拟议的研究将检验以下基本假设：抗生素的局部释放将消除 局部感染，恢复缺损部位的软组织愈合，并允许远端部位的骨骼生长健壮。 拟议的研究将通过两个具体目标来完成：1）制造和表征 利用不同抗生素装载方法的空间维持器的特性来了解抗生素的动力学 释放并确保机械性能足以进行下颌植入，并且 2) 评估 抗生素释放间隙维持器对体内大型动物模型下颌感染的影响 骨骼在 3D 打印生物反应器中靠近肋骨骨膜生长。空间维护者将通过以下方式进行评估 机械测试（压缩、4 点弯曲、螺钉拔出）和显微计算机断层扫描 (microCT) （用于孔径和孔隙率）。释放的抗生素浓度将通过高性能液体进行评估 色谱法（HPLC）。将利用细菌来确定抗生素的最低抑菌浓度。在 为了评估间隙保持器在体内的效果，将擦拭下颌部位（对于 鉴定、潜在抗生素耐药性测试）并将通过 microCT 分析骨生长和 组织和细胞类型的组织学。生物反应器中生长的组织将通过 microCT 和组织学进行分析 用于骨骼生长，采用定量聚合酶链反应 (qPCR)，并通过压缩和螺钉拔出 测试。在几个时间点抽取的血液将用于检测全身感染标志物，口腔拭子将用于检测感染的全身标记物。 进行培养，并监测生命体征（例如心率和体温）。 完成这些研究后，预期结果是成功制造空间保持器 能够释放抗生素并具有强大的机械性能，3D打印的成功利用 大型动物模型中的生物反应器，以及持续但尚未成功开发的大型动物模型 局部、下颌感染。除了改进现有策略之外，这项工作还将拓宽我们的范围 了解细菌、免疫反应、抗生素输送和骨骼生长之间的相互作用。 此外，所提出的系统为大或不寻常尺寸的复杂缺陷提供了一种治疗方法 由于形状或尺寸限制，无法利用传统的自体移植组织。