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

项目摘要/摘要 这个项目的理由是需要改进功能和美观的策略 因创伤、肿瘤切除、感染、先天畸形或 其他疾病。由于邻近的许多组织类型和附近有细菌充斥的口腔，修复 头面部组织很复杂。因此，这项研究的目标是开发新的方法和 利用支架促进软组织修复颅面骨组织的现有策略 修复和维持缺损的空间，局部释放抗生素以对抗感染，以及组织生长 在身体内远端部位的特定几何形状，以消除与自体移植相关的供体部位并发症 修理。这项拟议中的研究将检验局部释放抗生素将消除 局部感染，恢复缺损处的软组织愈合，并允许远端部位强劲的骨生长。 拟议的研究将通过两个具体目标来完成：1)制造和表征 不同抗生素载药方式下空间维持器的性能研究 松解并确保机械性能适合下颌种植；2)评估 抗生素释放间隙保持剂对大鼠下颌骨感染的影响 在3D打印的生物反应器中，骨骼与肋骨骨膜相邻生长。太空维护员将通过以下方式进行评估 机械测试(压缩、四点弯曲、螺丝拔出)和微型计算机断层扫描(MicroCT) (用于孔大小和孔隙率)。释放的抗生素浓度将通过高效液体进行评估 高效液相色谱(HPLC)。将利用细菌来确定抗生素的最低抑菌浓度。在……里面 为了评估在体空间维持器的效果，我们将擦拭下颌部位(用于 鉴定，测试潜在的抗生素耐药性)，并将通过MicroCT分析骨骼生长和 组织和细胞类型的组织学。在生物反应器中生长的组织将通过显微CT和组织学进行分析 用于骨生长，通过定量聚合酶链式反应(QPCR)以及通过加压和螺丝钉拔出 测试。在几个时间点抽取的血液将被用来检测感染的系统标志，口腔拭子将被用来 进行培养，并对生命指标(如心率和体温)进行监测。 在完成这些研究后，预期结果是成功地制造出空间维护器 能够释放抗生素并具有坚固的机械性能，成功使用3D打印 生物反应器在大型动物模型中的应用，以及大型动物模型的成功开发，具有持续、至今 局限性的下颌感染。除了改进现有的战略外，这项工作还将扩大我们的 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，建议的系统提供了一种治疗大型或不寻常尺寸的复杂缺陷的方法。 由于形状或大小的限制，无法使用传统的自体移植组织。

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.