Bioinspired Synthetic Grafts for Bone Regeneration

用于骨再生的仿生合成移植物

基本信息

批准号：
9551215
负责人：
Shyni Varghese
金额：
$ 34.8万
依托单位：
DUKE UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
2017
资助国家：
美国
起止时间：
2017-09-01 至 2019-05-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/9551215
关键词：
Adenosine Adverse effects Allografting Area Autologous Transplantation BMP2 gene Biocompatible Materials Biological Models Biomimetics Blood Blood Vessels Bone Regeneration Bone Tissue Bone Transplantation CXCR4 Receptors Calcified Calcinosis Calcium Cell physiology Cells Clinical Cues Defect Development Environment Exhibits Extracellular Matrix Failure Gene Expression Glycerol Goals Growth Factor Heterogeneity Histology Homeostasis Human Implant In Vitro Ions Laboratories Lateral Manuals Measures Mechanics Mediating Membrane Proteins Minerals Molecular Molecular Profiling Morbidity - disease rate Natural regeneration Osteoblasts Osteogenesis Palpation Performance Phase Play Polymers Property Proteins Recruitment Activity Regenerative Medicine Research Roentgen Rays Role Side Signal Transduction Site Stem cells Structure System Therapeutic Time Tissues Transplanted tissue Undifferentiated Vascular Endothelial Growth Factors Vascularization base biomineralization bone calcification calcium phosphate cost cost effective design disease transmission drug development in vivo infancy inorganic phosphate insight osteogenic programs public health relevance repaired sham surgery stem cell differentiation success tissue regeneration tissue repair

项目摘要

DESCRIPTION (provided by applicant): Synthetic systems that provide structural support while activating endogenous cells to form functional bone tissues have been considered as an optimal therapeutic strategy for treating critical bone defects. Currently, autografts and allografs are the primary choice of implants, but both suffer from various drawbacks such as donor site morbidity, scarcity, immunorejection, or disease transmission. In contrast, synthetic bone grafts with intrinsic osteoinductivity and osteogenicity could provide an easy-to-manufacture, cost-effective, and widely available therapeutic strategy for treating bone defects/failures. In the proposed study, we will investigate the efficacy of a fully synthetic bone grafts being developed in our laboratory to form in vitro and in vivo bone tissues. The biomimetic bone graft described here is developed by using principles of biomineralization, which leads to formation of a synthetic bone-like extracellular matrix that recapitulates various static and dynamic physicochemical cues of the native tissue including the dynamic dissolution/formation of mineral phase. Using this graft, we will: (1) determine the role of various physicochemical cues from the matrix and the mineral environment on osteogenic differentiation of stem cells in vitro, (2) elucidate the mechanism by which the biomineralized grafts exhibits osteogenicity and osteoinductivity, and (3) in vivo bone formation ability of the grafts by using posterolateral fusin as a model system. The grafts are designed to provide the structural and mechanical integrity required for bone grafting, while activating endogenous cells to promote bone formation. Such an endogenous cell-driven strategy in regenerative medicine has the potential to circumvent the limitations of existing approaches associated with cost, space, and time. Such an approach involving synthetic grafts devoid of any growth factors will also confine the bone formation to the implant site and overcome major side effects associated with growth factor-containing grafts. Though the proposed study is focused on bone tissue formation and repair, the biomimetic approach can be applied to study other cells/systems, thus having a far-reaching impact.

描述（由申请人提供）：在激活内源细胞形成功能性骨组织的同时提供结构支持的合成系统已被认为是治疗临界骨缺损的最佳治疗策略。目前，自体移植和同种植物是植入物的主要选择，但两者都有各种缺点，例如供体部位的发病率，稀缺，免疫反应或疾病传播。相比之下，具有内在骨诱导和成骨的合成骨移植物可以提供易于制造，具有成本效益且可广泛可用的治疗策略，可用于治疗骨缺损/失败。在拟议的研究中，我们将研究在实验室中开发出完全合成的骨移植物以形成体外和体内骨组织的功效。此处描述的仿生骨移植是通过使用生物矿化原理开发的，这导致形成合成骨样细胞外基质，该基质概括了天然组织的各种静态和动态的物理化学提示，包括动态溶解/形成矿相。 Using this graft, we will: (1) determine the role of various physicochemical cues from the matrix and the mineral environment on osteogenic differentiation of stem cells in vitro, (2) elucidate the mechanism by which the biomineralized grafts exhibits osteogenicity and osteoinductivity, and (3) in vivo bone formation ability of the grafts by using posterolateral fusin as a model system.移植物旨在提供骨移植所需的结构和机械完整性，同时激活内源性细胞以促进骨形成。这种内源性细胞驱动的再生医学策略有可能规避与成本，空间和时间相关的现有方法的局限性。这种涉及没有任何生长因子的合成移植物的方法也将使骨形成局限于植入部位并克服与含生长因子的移植物相关的主要副作用。尽管拟议的研究集中在骨组织的形成和修复上，但仿生方法可以应用于其他细胞/系统，从而产生深远的影响。