"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: 9750093
• 负责人: Emma Watson
• 金额: $ 4.41万
• 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 2020-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9750093
• 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 bone; craniofacial complex; craniofacial repair; craniofacial tissue; 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.

项目摘要/摘要 该项目的理由是基于改进功能和美学策略的需求 由创伤，清除，感染，先天性畸形或 其他疾病。由于许多组织类型近距离接近和附近的细菌口腔，因此修复 颅面组织很复杂。因此，这项研究的目的是开发新颖的方法和 利用脚手架促进软组织，改善颅面骨组织修复的现有策略 缺陷的愈合和空间维持，局部抗生素释放以作对抗感染以及组织生长 在体内遥远位点的指定几何形状，以消除与自体移植有关的供体部位的发病率 维修。拟议的研究将检验基本假设，即局部释放抗生素将消除 局部感染，在缺陷部位恢复软组织愈合，并在远端允许稳健的骨骼生长。 拟议的研究将通过两个具体目标来完成：1）制造和表征 空间维护者的特性利用不同的抗生素加载方法来了解抗生素的动力学 释放并确保机械性能足以适合下颌植入，2）评估 抗生素释放空间维护者对体内大动物模型中下颌感染的影响 骨骼在3D印刷的生物反应器中与肋骨相邻生长。空间维护者将通过 机械测试（压缩，四点弯曲，螺丝拉力）和微型层析成像（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）。细菌将用于确定抗生素的最低抑制浓度。在 为了评估体内太空维护者的影响，下颌位点将被擦拭（因为 鉴定，潜在抗生素抗性的测试），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和组织学分析 用于骨生长，具有定量聚合酶链反应（QPCR），并通过压缩和螺钉拉出 测试。在几个时间点抽取的血液将用于检测系统性标记，口腔拭子将 进行培养，将监测生命力（例如心率和温度）。 这些研究完成后，预期的结果是空间维护者的成功制造 能够具有鲁棒机械性能的抗生素释放，成功利用3D印刷 大型动物模型中的生物反应器，以及成功开发具有持续但持续的大型动物模型 局部，下颌感染。除了改进现有策略外，这项工作还将扩大我们的 了解细菌，免疫反应，抗生素递送和骨骼生长之间的相互作用。 此外，提出的系统为大型或不寻常大小的复杂缺陷提供了一种治疗方法 由于形状或尺寸限制，这无法利用传统的自体移植组织。

项目成果

A murine model of cutaneous aspergillosis for evaluation of biomaterials-based local delivery therapies.

用于评估基于生物材料的局部递送疗法的皮肤曲霉病小鼠模型。

• DOI: 10.1002/jbm.a.36671
• 发表时间: 2019
• 期刊: Journal of biomedical materials research. Part A
• 作者: Tatara,AlexanderM;Watson,Emma;Albert,NathanielD;Kontoyiannis,PanayiotisD;Kontoyiannis,DimitriosP;Mikos,AntoniosG
• 通讯作者: Mikos,AntoniosG

An Ovine Model of In Vivo Bioreactor-Based Bone Generation.

基于体内生物反应器的骨生成的绵羊模型。

• DOI: 10.1089/ten.tec.2020.0125
• 发表时间: 2020
• 期刊: Tissue engineering. Part C, Methods
• 作者: Watson,Emma;Tatara,AlexanderM;vandenBeucken,JeroenJJP;Jansen,JohnA;Wong,MarkE;Mikos,AntoniosG
• 通讯作者: Mikos,AntoniosG