Complex Nanocomposites for Bone Regeneration

用于骨再生的复杂纳米复合材料

基本信息

批准号：
7934472
负责人：
ANTONI P TOMSIA
金额：
$ 115.24万
依托单位：
UNIVERSITY OF CALIF-LAWRENC BERKELEY LAB
依托单位国家：
美国
项目类别：
财政年份：
2003
资助国家：
美国
起止时间：
2003-08-04 至 2014-05-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/7934472
关键词：
3-Dimensional Address Anatomy Animal Model Animals Apatites Architecture Area Asses Attention Autologous Autologous Transplantation Behavior Biochemical Biocompatible Materials Biodegradation Biological Biological Assay Biological Process Biological Sciences Biological Testing Biology Biomechanics Biomedical Engineering Biomimetics Bone Diseases Bone Growth Bone Regeneration Bone Resorption Bone Tissue Bone Transplantation Bone remodeling Breathing Calcified California Cell Adhesion Cell Culture Techniques Cells Chemicals Chemistry Complex Defect Dental Development Devices Dimensions Drug Delivery Systems Drug Formulations Engineering Environment Family Foreign-Body Reaction Fracture Freezing Future Goals Grant Growth Factor Healed Health Human Hybrids Hydrogels Implant In Vitro Infection Institution Interdisciplinary Study Laboratories Laws Lead Length Libraries Mechanics Medical Mesenchymal Stem Cells Metabolic Methods Minerals Miniature Swine Modeling Monitor Morbidity - disease rate Multipotent Stem Cells Mus Nanotechnology Natural regeneration Nature Nutrient Operative Surgical Procedures Organ Organ Transplantation Orthopedics Oryctolagus cuniculus Osteogenesis Outcome Parathyroid Hormones Pathway interactions Patients Penetration Performance Phase Philosophy Physiological Porosity Pre-Clinical Model Preparation Printing Process Property Protocols documentation Quality of life Research Resistance Risk San Francisco Science Scientist Series Signal Pathway Signaling Molecule Site Solubility Structure Supporting Cell Surface Suspension substance Suspensions System Techniques Testing Time Tissue Engineering Tissues United States Universities Vision Weight-Bearing state angiogenesis base bioresorption bone cell growth chemical release clinically relevant combinatorial craniofacial repair density design engineering design flexibility functional group healing human PTH protein implant material improved in vivo mineralization multidisciplinary nanocomposite nanoscale new technology novel osteogenic pre-clinical prevent programs public health relevance response sample fixation scaffold scale up skeletal standard of care success three dimensional structure tool wasting

项目摘要

DESCRIPTION (provided by applicant): This Bioengineering Research Partnership proposal is submitted by a multidisciplinary collaboration of scientists in the University of California (UC) system. The lead institution is Lawrence Berkeley National Laboratory, with component groups at UC Berkeley and UC San Francisco campuses. This BRP brings together expertise in materials sciences, chemistry, biology, and dental/medical science to begin the translational phase of this project. Our goal is to develop biomaterials for tissue engineering that will eliminate surgical risks and allow immediate return of function. We will develop and test new implant materials that can support mesenchymal stem cells and bone regeneration, by combining biomimetics with radically new design philosophies that consider anatomic and functional needs, customizing the scaffold to the skeletal defect. The ultimate goal is to develop a range of osteoinductive implant materials or scaffolds that function harmoniously with the surrounding native tissue. This long-term goal will provide materials for optimal repair of craniofacial and orthopedic skeletal defects that would otherwise require a bone graft from a second surgical site. First, hydrogels with varying mechanical responses and biodegradation rates will be synthesized. Different functional groups will be added to the hydrogel structure to template biomimetic mineralization of apatite and other biominerals-and to promote cell adhesion. Second, these materials, and others already developed for our current grant, will be used in the preparation of scaffolds with various compositions and architectures, including anatomically-inspired designs that considers both cortical and cancellous functional anatomy made by robocasting (3-D printing) and lamellar structures prepared using a novel technology developed in our laboratory based on freeze-casting of suspensions. Third, the addition of diverse functional capabilities to these porous scaffolds will be systematically explored. Materials deemed to display optimal mechanical responses will be tested in cell culture and then in vivo in mice, using standardized bone formation assays that allow assessment of the rate and extent of new bone formation. Based on these results, we will select scaffolds that have the greatest translational potential. These will be tested in combination with autologous multipotent stem cells for the ability to promote bone formation in established medium-sized (rabbit) and large-sized (mini-pig) animal models utilizing a consistent protocol of biomechanical and biological assays that will also serve to asses key biological process that determine scaffold integration. Successful completion of these studies will result in the identification of new materials suitable for testing for the repair of craniofacial and orthopedic skeletal defects in humans. The present standard of care for such defects may be altered to eliminate bone grafts, decrease risks to patients, improve quality of life, and increase the armamentarium of the clinician. PUBLIC HEALTH RELEVANCE: The demand for biomaterials to assist or replace organ functions is rapidly increasing. Every year, more than one million patients in the United States with skeletal defects require bone graft procedures. This application will develop novel biomaterials for optimal repair of craniofacial and orthopedic skeletal defects that would otherwise require a bone graft from a second surgical site. Improvement of implants will result in improved health and quality of life for the millions of people who will need implants in the future.

描述（由申请人提供）：该生物工程研究合作伙伴提案由加州大学 (UC) 系统的多学科科学家合作提交。牵头机构是劳伦斯伯克利国家实验室，在加州大学伯克利分校和加州大学旧金山分校设有组成小组。该 BRP 汇集了材料科学、化学、生物学和牙科/医学领域的专业知识，以开始该项目的转化阶段。我们的目标是开发用于组织工程的生物材料，消除手术风险并立即恢复功能。我们将通过将仿生学与考虑解剖和功能需求的全新设计理念相结合，开发和测试能够支持间充质干细胞和骨再生的新型植入材料，根据骨骼缺陷定制支架。最终目标是开发一系列与周围天然组织和谐发挥作用的骨诱导植入材料或支架。这一长期目标将为颅面和骨科骨骼缺陷的最佳修复提供材料，否则需要从第二个手术部位进行骨移植。首先，将合成具有不同机械响应和生物降解速率的水凝胶。水凝胶结构中将添加不同的官能团，以模拟磷灰石和其他生物矿物质的仿生矿化，并促进细胞粘附。其次，这些材料以及我们目前资助下开发的其他材料将用于制备具有各种成分和结构的支架，包括通过机器人铸造（3D 打印）制作的考虑皮质和松质功能解剖结构的解剖学设计。以及使用我们实验室开发的基于悬浮液冷冻铸造的新技术制备的层状结构。第三，将系统地探索向这些多孔支架添加多种功能。被认为表现出最佳机械反应的材料将在细胞培养物中进行测试，然后在小鼠体内进行测试，使用标准化的骨形成测定来评估新骨形成的速率和程度。根据这些结果，我们将选择具有最大转化潜力的支架。这些将与自体多能干细胞结合使用一致的生物力学和生物测定方案在已建立的中型（兔子）和大型（小型猪）动物模型中进行促进骨形成的能力进行测试，该方案也将用于评估决定支架整合的关键生物过程。这些研究的成功完成将导致鉴定出适合测试人类颅面和骨科骨骼缺陷修复的新材料。可以改变目前针对此类缺陷的护理标准，以消除骨移植、降低患者风险、提高生活质量并增加临床医生的装备。公共卫生相关性：对辅助或替代器官功能的生物材料的需求正在迅速增加。每年，美国有超过一百万患有骨骼缺陷的患者需要骨移植手术。该应用将开发新型生物材料，用于最佳修复颅面和骨科骨骼缺陷，否则需要从第二个手术部位进行骨移植。植入物的改进将改善未来数百万需要植入物的人的健康和生活质量。