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Cellular and Mechanical Mechanisms Regulating Mandibular Distraction Osteogenesis

调节下颌牵张成骨的细胞和机械机制

基本信息

批准号：
9281376
负责人：
MICHAEL T LONGAKER
金额：
$ 37.48万
依托单位：
STANFORD 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：
2017-04-01 至 2022-03-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/9281376
关键词：
Address Anatomy Animal Model Biology Biomechanics Blood Circulation Bone Regeneration Bone Tissue Bone Transplantation Bone callus Cell Differentiation process Cells Cephalic Characteristics Chimerism Complex Confocal Microscopy Controlled Environment Cornea Defect Deformity Dental Development Dissection Distraction Osteogenesis Elements Endosteum Epithelial Excision Face Fluorescence Fluorescence-Activated Cell Sorting Focal Adhesion Kinase 1 Focal Adhesions Freezing Genetic Goals Harvest Health Expenditures Histologic Impairment In Vitro Incisor Injection of therapeutic agent Knockout Mice Knowledge Label Limb structure Malocclusion Mandible Mandibular distraction Mandibulofacial Dysostosis Manuscripts Mechanics Mediating Mesenchyme Methods Molecular Morbidity - disease rate Mus Natural regeneration Neurologic Operative Surgical Procedures Osteogenesis Osteotomy Parabiosis Pathway interactions Patients Periosteum Plant Roots Play Population Process Protocols documentation Publishing Recruitment Activity Regenerative response Reporter Research Research Proposals Robin bird Role Secondary to Signal Pathway Signal Transduction Site Skeleton Source Stem cells Stimulus Tamoxifen Techniques Therapeutic TimeLine Tissue Engineering Tissues Tooth root structure Transgenic Mice Transplanted tissue Trauma biomaterial compatibility bone cell determination cellular transduction congenital anomaly craniofacial craniofacial microsomia disability distraction improved in vivo inhibitor/antagonist mechanical force mechanotransduction mouse model novel novel strategies osteogenic peripheral blood progenitor reconstruction response skeletal small molecule inhibitor stem success tool trafficking treatment choice tumor

项目摘要

Project Summary Craniofacial skeletal deficiencies involving the mandible, midface, and cranial vault result in a wide range of disabilities including severe airway compromise, malocclusion, inadequate corneal protection, and neurological impairment. Secondary to trauma, tumor resection, or developmental anomalies, these deformities represent a significant reconstructive challenge and account for over $1 billion in annual health care expenditures. While surgical techniques integrating conventional osteotomies with autogenous bone and/or synthetic graft materials can be successful, limitations in donor site morbidity, biocompatibility, and osteoconductivity still remain. As an alternative approach, distraction osteogenesis (DO) offers the ability to promote endogenous bone formation across a mechanically controlled environment, providing anatomical and functional replacement of deficient tissue. The application of DO to the craniofacial skeleton has revolutionized the treatment of many congenital and acquired defects, and for many patients with mandibular deficiency associated with Pierre-Robin sequence, Treacher Collins syndrome, and craniofacial microsomia, distraction osteogenesis has become the treatment choice. We have developed a novel model of mouse mandibular distraction which allows for lineage tracing of cellular contribution to the regenerate and genetic dissection of biomechanical force transduction regulating cell differentiation during guided bone formation. Findings from this proposal will deepen our knowledge of how progenitor cells localize to the regenerate and enhance our understanding of craniofacial distraction. The identification of the cellular source within the DO regenerate, the timeline for progenitor cell response, and determination of how these cells transduce physical stimuli to enact a regenerative response may all facilitate development of improved distraction protocols. Findings from this proposal may provide new and effective strategies for reconstruction of the craniofacial skeleton.

项目总结