Vascularization and Bone Repair

血管化和骨修复

• 批准号: 7096011
• 负责人: ROBERT E GULDBERG
• 金额: $ 25.25万
• 依托单位: GEORGIA INSTITUTE OF TECHNOLOGY
• 依托单位国家: 美国
• 财政年份: 2004
• 资助国家: 美国
• 起止时间: 2004-07-01 至 2008-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7096011
• 关键词: angiogenesis; biomaterial interface interaction; biomechanics; biotechnology; bone disorder; bone regeneration; cell adhesion; computed axial tomography; histology; implant; laboratory rat; medical implant science; musculoskeletal circulation; normal ossification; polymers; surface coating; surface property; tissue /cell culture; tissue engineering; tissue support frame

DESCRIPTION (provided by applicant): The requirements for bone repair, whether provided by the host or within an implantable tissue-engineered construct, include an extracellular matrix scaffold, cells, a functional vascular supply, and osteoinductive factors. Of these essential elements, vascular supply has been the least studied in the context of tissue engineering in part due to the difficulty in quantifying 3-D vascular structures within tissues. Traditionally, 2-D histological analysis has been used to assess vessel density. However, this approach is semi-quantitative at best and does not easily allow analysis throughout the tissue. High-resolution 3-D microcomputed tomography (micro-CT) imaging coupled with contrast agent perfusion has the potential to overcome these limitations to quantify vascular growth. The recent development of in vivo micro-CT systems has further provided the opportunity to non-invasively monitor mineralized matrix formation within a bone defect in vivo. The goal of this application is to combine and extend these methodologies to better understand the temporal and spatial relationships between vascularization and mineralization in a well defined in vivo bone tissue engineering model. The Specific Aims are to: I. Quantify 3-D vascular growth and mineralized matrix formation within scaffolds implanted into critically-sized segmental bone defects, II. Analyze the influence of porous scaffold architecture on vascular invasion and mineralization, and III. Test the effect of adding a cellular component to implanted constructs on vascularization and mineralization during segmental defect repair. The proposed research is highly significant because it integrates quantitative 3-D imaging techniques with a well characterized in vivo model to better understand the inter-relationship between two processes essential to bone repair: vascularization and mineralization. Lack of a vigorous vascular response may be an important mechanism of delayed or failed bone repair. Decoupling of vascularization and mineralization responses is also possible during for example fibrous tissue repair. The restoration of a functional vascular supply is a critical issue for engineering the repair of a wide variety of tissues in addition to bone. Thus, the proposed studies will establish a valuable new approach for assessing the integration of tissue-engineered constructs into living systems. Furthermore, the developed methodologies will have broad applicability to other research areas, including for example studies on fracture healing, skeletal development, vascular injury, and tumorigenesis.

描述（由申请人提供）：骨修复的要求，无论是由宿主提供还是在可植入的组织工程构建体内提供，都包括细胞外基质支架、细胞、功能性血管供应和骨诱导因子。在这些基本要素中，血管供应在组织工程的背景下研究得最少，部分原因是难以量化组织内的3-D血管结构。传统上，2-D组织学分析已被用于评估血管密度。然而，这种方法充其量是半定量的，并且不容易允许在整个组织中进行分析。高分辨率3-D微计算机断层扫描（micro-CT）成像结合造影剂灌注有可能克服这些限制，以量化血管生长。体内微型CT系统的最新发展进一步提供了无创监测体内骨缺损内矿化基质形成的机会。本申请的目的是联合收割机和扩展这些方法，以更好地理解在一个明确的体内骨组织工程模型中血管化和矿化之间的时间和空间关系。具体目标是：一。量化三维血管生长和矿化基质形成支架植入到关键大小的节段性骨缺损，II。分析多孔支架结构对血管侵袭和矿化的影响，III.测试在节段性缺损修复过程中向植入结构中添加细胞成分对血管化和矿化的影响。 这项拟议的研究非常重要，因为它将定量3D成像技术与表征良好的体内模型相结合，以更好地了解骨修复所必需的两个过程之间的相互关系：血管化和矿化。缺乏有力的血管反应可能是骨修复延迟或失败的重要机制。在例如纤维组织修复期间，血管化和矿化反应的解耦也是可能的。功能性血管供应的恢复对于除骨之外的各种组织的工程修复是关键问题。因此，拟议中的研究将建立一个有价值的新方法来评估组织工程结构融入生命系统。此外，开发的方法将具有广泛的适用性，其他研究领域，包括例如骨折愈合，骨骼发育，血管损伤和肿瘤发生的研究。