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Engineering Bone Cell Migration Via Mechanotaxis

Engineering Bone Cell Migration Via Mechanotaxis
通过机械趋向性工程骨细胞迁移
批准号:
7083558
负责人:
Andrew J Putnam
金额:
$6.89万
依托单位国家:
美国
项目类别:
财政年份:
2005
资助国家:
美国
项目状态:
已结题
起止时间:
2005-07-01 至 2007-06-30

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中文摘要
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英文摘要
DESCRIPTION (provided by applicant): A new form of directed cell migration, called mechanotaxis (or durotaxis), in which both speed and directional persistence are influenced by substrate mechanical properties, has been recently described in the literature. Exploiting mechanotaxis therapeutically, in conjunction with chemotaxis and haptotaxis, may represent a new approach to designing biomaterials that provide the appropriate combinations of chemical and mechanical cues to promote the selective migration of osteoblasts (or mesenchymal stem cells) from surrounding healthy tissue into small bony defects. Prior to pursuing craniofacial tissue engineering applications, additional basic science studies addressing the relevance of mechanotaxis for bone, combined with efforts to determine the mechanisms by which cells sense their local mechanical environment to initiate a program of cell motility, are required. This R03 application proposes a set of feasibility studies to determine if a pre-osteoblastic cell line (MC3T3-E1) will migrate via mechanotaxis on model substrates. Specifically, this proposal aims to: 1.) Fabricate polyacrylamide hydrogels with pre-defined mechanical compliance using a photopolymerization process, and to subsequently functionalize these hydrogels with extracellular matrix (ECM) proteins to support MC3T3-E1 adhesion and spreading; 2.) Quantify cell migration speed and directional persistence of MC3T3-E1 cells on ECM-modified hydrogel substrates possessing uniform stiffness, sharp interfaces in stiffness, or gradients in stiffness; and 3.) Determine what role, if any, is played by the Rho GTPases in sensing substrate compliance and regulating the mechanotactic response. Successful completion of these aims will not only provide useful fundamental data regarding cell migration mechanisms, but may also guide future osteoconductive strategies that exploit this mechanotaxis paradigm. Such strategies will be explored in the applicant's future R21 and R01 proposals.
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2023 Biomaterials and Tissue Engineering
  • 批准号:
    10675948
  • 项目类别:
  • 资助金额:
    $1.3万
  • 财政年份:
    2023
  • 负责人:
    Andrew J Putnam
  • 依托单位:
Preformed vascular modules designed for inosculation with host tissue
Preformed vascular modules designed for inosculation with host tissue
Preformed vascular modules designed for inosculation with host tissue