权益分类	功能权益	普通用户	{{item.name}}会员
{{category.name}}	{{benefitItem.name}}

Multicomponent Composites for Bioengineering of Dental Bone Tissue

用于牙骨组织生物工程的多组分复合材料

基本信息

批准号：
8810667
负责人：
Amol Vijay Janorkar
金额：
$ 11.44万
依托单位：
UNIVERSITY OF MISSISSIPPI MED CTR
依托单位国家：
美国
项目类别：
财政年份：
2014
资助国家：
美国
起止时间：
2014-02-20 至 2017-01-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8810667
关键词：
Adhesions Age Antibiotics Bacterial Infections Behavior Biochemical Biocompatible Biocompatible Materials Bioglass Bioglass 45S5 Biological Biomedical Engineering Biomedical Technology Bone Morphogenetic Proteins Bone Regeneration Bone Tissue Cell Survival Cell physiology Ceramics Characteristics Collagen Cytoskeleton Data Defect Dental Dental Implants Dentistry Development Doxycycline Drug Delivery Systems Edentulous Mouth Elastin Electron Microscopy Engineering Environment Excision Exhibits Future Genetic Engineering Growth Growth Factor Healed Health Infection Infiltration Inflammation Investigation Lead Matrix Metalloproteinase Inhibitor Measures Mechanics Membrane Methodology Modeling Morbidity - disease rate Operative Surgical Procedures Oral Osteoblasts Osteogenesis Patients Pharmaceutical Preparations Phase Transition Polymers Population Process Property Proteins Quality of life Research Site Solutions Stimulus Structure Surface System Techniques Temperature Tensile Strength Testing Tissue Engineering Tissues Tooth Extraction Tooth Loss Tooth structure Trauma Work base biomaterial compatibility bone controlled release design healing improved innovation maxillofacial membrane activity mineralization novel polypeptide recombinant human bone morphogenetic protein-2 reconstruction response soft tissue tissue culture tumor two-dimensional

项目摘要

DESCRIPTION (provided by applicant): Maxillofacial bony defects, occurring as a result of tumor resection, infection, trauma, as well as tooth loss or extraction, are often associated with patient morbidity. Development of suitable biomaterials for reconstruction of oral structures through guided bone regeneration (GBR) has reduced morbidity, improved quality of life after surgery, and has benefitted partially or completely edentulous patients by supporting dental implants used to replace the lost teeth. The GBR techniques primarily use a polymeric barrier membrane to stop infiltration of surrounding undesired soft tissue into the defect site and support new bone formation. Currently available barrier membranes display significant shortfalls. For example, the non- bioresorbable membranes need a second surgery for their removal after tissue healing. The synthetic, bioresorbable membranes eliminate this need for the second surgery and provide sufficient mechanical strength but they lead to local inflammation during degradation. The natural, bioresorbable membranes (primarily collagen) eliminate inflammation, but still suffer from rapid degradation and inadequate mechanical strength. More importantly, none of these membranes offer a tunable release of bioactive agents (osteoinductive proteins, growth factors, antibiotics) to enhance the new bone tissue formation. Therefore, it is desirable to have a biomaterial with suitable biocompatibility, mechanical properties, and bioactive agent release. We propose to prepare novel multi-component composite membranes that incorporate a stimulus- responsive smart polymer (elastin-like polypeptide, ELP), biodegradable ceramic (45S5 Bioglass), and collagen as network former. The major component, ELP, is genetically engineered to provide precise control of its properties and exhibits an inverse phase transition behavior in response to changes in its solution environment. We hypothesize that incorporation of ELP and Bioglass will improve the mechanical properties of the membranes, while the inverse phase transition behavior of ELP will control the release rates of bioactive agents from the membranes. This research is divided into following key Specific Aims: (1) Create and Characterize ELP-Bioglass-Collagen Membranes; (2) Characterize Drug Release Profiles for Composite Membranes; (3) Evaluate Drug-loaded ELP-Bioglass-Collagen Membranes for Osteoblast Culture. Our research will significantly impact major technological and biological problems that currently limit the development of barrier membranes for simultaneous drug delivery and tissue engineering in GBR and help achieve: (1) sustained release of bioactive agents; (2) improved bone tissue growth; and (3) reduced post- surgical bacterial infections and infiltration of surrounding undesired soft tissue. While advancing the fundamental understanding of extra-cellular matrix-based composites, our research will provide new composite materials for GBR and other applications requiring bone replacement. Thus, the new ELP- Bioglass-Collagen materials may directly impact biomedical technology in the near future.

描述（由申请人提供）：由于肿瘤切除、感染、创伤以及牙齿缺失或拔除而发生的颌面骨缺损通常与患者发病率相关。通过引导骨再生（GBR）重建口腔结构的合适生物材料的开发降低了发病率，改善了术后生活质量，并通过支持用于替换缺失牙齿的牙科种植体使部分或完全缺牙患者受益。GBR技术主要使用聚合物屏障膜来阻止周围不需要的软组织渗入缺损部位并支持新骨形成。目前可用的阻隔膜显示出显著的不足。例如，不可生物吸收的膜需要第二次手术以在组织愈合后将其移除。合成的生物可吸收膜消除了对第二次手术的需要，并提供了足够的机械强度，但它们在降解过程中导致局部炎症。天然的生物可吸收膜（主要是胶原蛋白）消除炎症，但仍然遭受快速降解和机械强度不足。更重要的是，这些膜都不能提供生物活性剂（骨诱导蛋白、生长因子、抗生素）的可调释放，以增强新骨组织的形成。因此，期望具有合适的生物相容性、机械性能和生物活性剂释放的生物材料。我们提出制备新型多组分复合膜，其包含刺激响应智能聚合物（弹性蛋白样多肽，ELP）、可生物降解陶瓷（45 S5生物玻璃）和胶原蛋白作为网络形成剂。主要成分ELP经过基因工程改造，可精确控制其性质，并在溶液环境变化时表现出逆相变行为。我们推测，ELP和生物玻璃的掺入将改善膜的机械性能，而ELP的逆相变行为将控制生物活性剂从膜的释放速率。本研究分为以下主要具体目的：（1）创建和表征ELP-生物玻璃-胶原膜;（2）表征复合膜的药物释放特性;（3）评价载药ELP-生物玻璃-胶原膜用于成骨细胞培养。我们的研究将显著影响目前限制用于GBR中的同时药物递送和组织工程的屏障膜的发展的主要技术和生物学问题，并有助于实现：（1）生物活性剂的持续释放;（2）改善骨组织生长;和（3）减少手术后细菌感染和周围不期望的软组织的浸润。在推进对细胞外基质基复合材料的基本理解的同时，我们的研究将为GBR和其他需要骨替代的应用提供新的复合材料。因此，新的ELP-生物玻璃-胶原材料可能在不久的将来直接影响生物医学技术。