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Reducing dose requirement of BMP-2 for osseous regeneration by microgeometry-indu

通过微观几何学降低骨再生所需的 BMP-2 剂量

基本信息

批准号：
8626709
负责人：
MOHAMED N RAHAMAN
金额：
$ 36.54万
依托单位：
MISSOURI UNIVERSITY OF SCIENCE & TECHNOLOGY
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：
2014-04-06 至 2017-09-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8626709
关键词：
Alkaline Phosphatase Allografting Area Autologous Autologous Transplantation Biocompatible Materials Biological Assay Biomedical Research Bone Morphogenetic Proteins Bone Regeneration Bone Resorption Bone Substitutes Bone Transplantation Calvaria Cleaved cell Cleft Palate Clinical Collaborations Defect Dose Enzyme-Linked Immunosorbent Assay Faculty Floor Genes Gold Growth Factor Healed Heating Histologic Hydroxyapatites Immune response In Vitro Inferior Institutes Laboratories Maxilla Maxillary Sinus Mesenchymal Stem Cells Microspheres Modeling Morbidity - disease rate Natural regeneration Operative Surgical Procedures Orthopedics Osteogenesis Outcome Patients Phase Physiological Pilot Projects Procedures Property Publishing Rattus Reporting Research Research Activity Series Site Structure Students Surface Testing Training Trauma Work alveolar bone bone bone morphogenetic protein 2 clinical application clinically significant cost cost effective craniofacial healing improved in vivo novel osteogenic physical conditioning programs public health relevance scaffold success

项目摘要

Abstract Periodontal and craniofacial surgeries frequently require bone regeneration when patients suffer from severely resorbed alveolar bone and poor maxillary floor, craniofacial trauma, or congenital cleft palate. Current treatments rely on osteoinductive autografts and allografts to induce clinically significant bone regeneration whereas osteoconductive bone substitutes cannot. However, autografts are limited by availability and second morbidity and allografts are limited by inferior and unpredictable healing outcomes. Osteogenic bone morphogenetic proteins (such as BMP-2) are potent bone inducer therefore they are very attractive for periodontal and craniofacial bone regeneration. However, traditionally BMPs are only effective at supraphysiological doses which can induce significant complications and high surgery cost. Reducing dose requirement is urgently needed for their safer and cost-effective clinical use. We hypothesize a new intrinsically osteoinductive biomaterial can reduce the dose requirement of BMP-2 while serve as an osteoconductive scaffold. We propose a compensating or synergistic effect may significantly promote bone formation because of the combination, and the BMP-2 dose requirement will decrease with the increase of the level of the intrinsic osteoinductive ability. Such a combined approach has not been reported yet. A novel micro-concave hydroxyapatite hemispheres (McHAs) will be developed for the study. To test our hypothesis, we propose to (1) Develop high-quality McHAs with controlled micro-concavity size and degradation rate that can induce varied osteoinductive-like ability; (2) In vitro examine the osteoinductive-like property of McHAs; (3) In vitro evaluate the effect of McHAs on dose requirement of BMP-2 (4) In vivo evaluate the effect of McHAs on dose requirement of BMP-2. The success of the project will generate a new type of clinically safer, cost-effective bone graft substitute that can greatly improve osseous regeneration in periodontal and craniofacial surgeries. In addition, the research activity will significantly enrich and strengthen the biomedical research initiatives at our institute, by prompting new research themes, promoting collaboration among departments, faculty and laboratories, and training students in our biomedical related programs.

摘要牙周病和颅面手术经常需要骨再生时，患者患有严重吸收的牙槽骨和较差的上颌底、颅面创伤或先天性腭裂。目前的治疗依赖于骨诱导自体移植物和同种异体移植物，以诱导临床显著的骨而骨传导性骨替代物不能。然而，自体移植物受到可用性的限制第二种发病率和同种异体移植物受到较差和不可预测的愈合结果的限制。成骨骨形态发生蛋白（如BMP-2）是有效的骨诱导剂，因此它们对于牙周和颅面骨再生。然而，传统上BMP仅在以下情况下有效：超生理剂量，这可能导致严重的并发症和高手术成本。减量迫切需要其更安全和具有成本效益的临床使用。我们假设一种新的内在的骨诱导性生物材料在作为骨传导材料的同时，可以降低BMP-2的剂量需求脚手架我们提出一种补偿或协同效应可能会显著促进骨形成， BMP-2的剂量需求将随着内源性BMP-2水平的增加而降低。骨诱导能力这种综合办法尚未得到报告。一种新型微凹将为研究开发羟基磷灰石半球（McHA）。为了验证我们的假设，我们建议（1）开发具有可控微球尺寸和降解速率的高质量McHAs，（2）体外检测McHAs的类骨诱导活性;（3）体外评价McHAs的类骨诱导活性 McHAs对BMP-2剂量需求的影响（4）体内评价McHAs对剂量需求的影响 BMP-2的要求。该项目的成功将产生一种新型的临床安全，骨移植替代物，可以大大促进牙周和颅面手术中的骨再生。此外，研究活动将大大丰富和加强生物医学研究举措，我们的研究所，通过促进新的研究主题，促进部门，教师和实验室，并在我们的生物医学相关项目中培训学生。