Calvarial Regeneration using Biomatrix-Encapsulated Skeletal Progenitors

使用生物基质封装的骨骼祖细胞进行颅骨再生

基本信息

批准号：
7936866
负责人：
Annelise Emily Barron
金额：
$ 106万
依托单位：
STANFORD UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
2009
资助国家：
美国
起止时间：
2009-09-23 至 2011-08-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/7936866
关键词：
1 year old Accidents Address Adipose tissue Age-Years Binding Biomedical Engineering Bone Cements Bone Matrix Bone Regeneration Bone Transplantation Calvaria Cell Adhesion Cell Survival Cell Therapy Cell Transplants Cell surface Cells Cellularity Cephalic Chronic Clinical Complex Congenital Abnormality Congenital Disorders Defect Deformity Development Devices Encapsulated Face Fibrous capsule of kidney Fluorescence Fluorescence-Activated Cell Sorting Fluorescent in Situ Hybridization Future Gel Genetic Transcription Goals Gold Growth Growth Factor Head Healed Histology Human Hydrogels Image Immunodeficient Mouse Implant In Situ Individual Infant Infection Life Liquid substance Malignant Neoplasms Membrane Proteins Methods Microcapsules drug delivery system Microfluidic Microchips Microfluidics Modeling Monitor Morbidity - disease rate Mus Natural regeneration Operative Surgical Procedures Patients Peptides Population Preclinical Testing Process Proteins Protocols documentation Public Health Receptor Signaling Risk Role Signal Pathway Site Skeleton Speed Staging Stem cells Structure Surface System Techniques Testing Therapeutic Time Tissue Engineering Tissues Transfection Translating Translations Transplantation Trauma Work base bone bone morphogenetic protein 2 capsule craniofacial cranium crosslink detector healing improved in vivo innovation interdisciplinary approach interest morphogens novel osteochondral tissue osteogenic point of care progenitor prospective public health relevance reconstruction regenerative research clinical testing research study response scaffold skeletal skeletal regeneration skeletal tissue stem stem cell biology tissue regeneration tomography tool two-photon

项目摘要

DESCRIPTION (provided by applicant): Debilitating craniofacial skeletal defects, which occur frequently as a result of congenital disorders, trauma, cancer, and surgical interventions, are some of the most challenging problems for reconstruction. While infants demonstrate the ability to heal large and complex calvarial defects, those older than one year of age have an insufficient healing response to even small skull defects. Although a plethora of strategies have been developed over the past century, the patchwork of methods currently available reflects the inadequacies of each therapeutic technique. In this regard, skeletal stem cell biology holds enormous untapped promise for future tissue engineering applications. The goal of this project is to make autogenous skeletal progenitor cell-based craniofacial skeletal regeneration a clinical reality. Using an interdisciplinary approach, we will bring together our expertise in stem cell biology, bioengineering, and craniofacial surgery to tackle the roadblocks to translation of cell-based skeletal tissue engineering. In Specific Aim 1, we will prospectively isolate pure populations of human skeletal progenitor cells from different tissues and identify key progenitor cell niche factors necessary for their expansion and differentiation. In Specific Aim 2, we will develop a novel high throughput, microfluidics-based FACS (MF-FACS) device for simultaneous isolation and encapsulation of individual skeletal progenitor cells in a hydrogel-based, microenvironment conductive to their regenerative capabilities. In Specific Aim 3, we will assess the regenerative potential of transplanted encapsulated skeletal progenitors in critical-sized calvarial defect models. The role of supplementary niche factors will be further assessed using a tunable macroscale hydrogel scaffolding material. We believe this highly innovative project will ultimately produce an effective cell-based craniofacial skeletal regeneration regiment suitable for clinical testing. PUBLIC HEALTH RELEVANCE: The current tools available to doctors to repair bone structures of the head and face damaged from accidents, birth defects or cancer are inadequate. Using cells that have been removed from the patient, this project seeks to identify, protect, and return only those cells capable of growing into new bone structures. We seek to improve public health by developing a point-of-care method for surgical reconstruction of living bone.

描述（由申请人提供）：使颅面骨骼缺陷使人衰弱，由于先天性疾病，创伤，癌症和手术干预措施经常发生，这是重建的一些最具挑战性的问题。尽管婴儿表现出可以治愈大而复杂的钙钙缺损的能力，但年龄在一岁以上的人对即使是小颅骨缺陷也没有足够的愈合反应。尽管过去一个世纪已经开发了大量策略，但目前可用的方法反映了每种治疗技术的不足。在这方面，骨骼干细胞生物学对将来的组织工程应用具有巨大的未开发的承诺。该项目的目的是使自体骨骼祖细胞基于基于颅面的颅面骨骼再生成为临床现实。使用跨学科的方法，我们将汇集我们在干细胞生物学，生物工程和颅面手术方面的专业知识，以应对障碍的障碍，以翻译基于细胞的骨骼组织工程。在特定的目标1中，我们将前瞻性地将人类骨骼祖细胞的纯种群与不同的组织分离，并确定其扩展和分化所需的关键祖细胞细胞生态位。在特定目标2中，我们将开发出一种新型的高通量，基于微流体的FACS（MF-FACS）设备，用于在基于水凝胶的微环境导电中同时隔离和封装单个骨骼祖细胞，以与其再生能力。在特定的目标3中，我们将评估关键尺寸大小的颅缺陷模型中移植封装的骨骼祖细胞的再生潜力。补充利基因素的作用将使用可调的宏观水凝胶脚手架材料进一步评估。我们认为，这个高度创新的项目最终将产生一个有效的基于细胞的颅面骨骼再生团，适合临床测试。公共卫生相关性：当前可用于修复因事故，出生缺陷或癌症而受损的头部和面部骨骼结构的工具不足。该项目使用已从患者中删除的细胞，旨在识别，保护和返回那些能够生长成新骨结构的细胞。我们试图通过开发一种护理方法来改善公共卫生的生命骨骼。