Craniofacial Tissue Engineering

颅面组织工程

• 批准号: 6891209
• 负责人: Gordana Vunjak-Novakovic
• 金额: $ 59万
• 依托单位: COLUMBIA UNIV NEW YORK MORNINGSIDE
• 依托单位国家: 美国
• 财政年份: 2005
• 资助国家: 美国
• 起止时间: 2005-09-01 至 2010-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6891209
• 关键词: bioengineering /biomedical engineering; biomaterial development /preparation; biomechanics; biomedical equipment development; bioreactors; biotechnology; bone morphogenetic proteins; cartilage development; cell differentiation; clinical research; computed axial tomography; human tissue; magnetic resonance imaging; mandibular condyle; mathematical model; osteogenesis; stem cells; tissue /cell culture; tissue /cell preparation; tissue engineering; tissue support frame

DESCRIPTION (provided by applicant): The clinical utility of tissue engineering depends upon our ability to direct cells to form tissues with characteristic structural and mechanical properties across different hierarchical scales. Ideally, an engineered graft should be autologous and tailored to (re)establish the structure and function of a lost or damaged tissue. Engineered tissues with such a high level of structural and functional complexity would also foster fundamental research by serving as physiologically relevant models for controlled quantitative studies. The application is for tissue engineering of human stratifed grafts suitable for mandibular condyle replacement, a tissue of great clinical interest and an excellent model for studies of stem cell differentiation and functional assembly into craniofacial tissues. We hypothesize that craniofacial structures with physiological gradients of structural and mechanical properties can be grown in vitro by biophysical regulation of adult human stem cells. We thus propose to engineer mandibular tissue grafts by culturing adult human stem cells on specialized scaffolds in advanced bioreactors. Aim 1 will focus on the development of modular bioreactors with environmental control, interstitial flow, mechanical loading and imaging compatibility. Aim 2 will focus on the development of silk protein scaffolds with spatial gradients of immobilized growth factors. In Aim 3, the advanced scaffolds and bioreactors will be utilized to engineer human tissue constructs with structural and mechanical properties resembling those of native condyles. The resulting grafts are expected to have sufficiently high fidelity for use in studies of stem cell responses to genetic and environmental signals and to yield tissue grafts for further studies and eventual application in regenerative medicine. Our overall scientific goal is to obtain new critical information that will improve our understanding of the phenomena and mechanisms involved in human stem cell differentiation during cranio- and orofacial tissue development. The related practical goal is to establish in vitro systems that can be used to study the self-renewal and differentiation of stem cells in a manner predictable of their behavior in vivo, and to custom-design tissue grafts by directed differentiation of human stem cells.

描述（由申请人提供）：组织工程的临床实用性取决于我们指导细胞形成具有跨不同层次尺度的特征结构和机械特性的组织的能力。理想情况下，工程移植物应该是自体的，并经过定制以（重新）建立丢失或受损组织的结构和功能。具有如此高水平的结构和功能复杂性的工程组织也将通过充当受控定量研究的生理相关模型来促进基础研究。该应用适用于适用于下颌骨髁置换的人体分层移植物的组织工程，这是一种具有重大临床意义的组织，也是研究干细胞分化和功能组装成颅面组织的优秀模型。我们假设具有结构和机械特性生理梯度的颅面结构可以通过成人干细胞的生物物理调节在体外生长。因此，我们建议通过在先进生物反应器的专门支架上培养成人干细胞来设计下颌组织移植物。目标 1 将重点开发具有环境控制、间隙流、机械负载和成像兼容性的模块化生物反应器。目标 2 将重点开发具有固定生长因子空间梯度的丝蛋白支架。在目标 3 中，先进的支架和生物反应器将用于设计具有类似于天然髁的结构和机械特性的人体组织结构。由此产生的移植物预计具有足够高的保真度，可用于研究干细胞对遗传和环境信号的反应，并产生用于进一步研究和最终应用于再生医学的组织移植物。我们的总体科学目标是获得新的关键信息，以提高我们对颅骨和口面部组织发育过程中人类干细胞分化所涉及的现象和机制的理解。相关的实际目标是建立体外系统，可用于以可预测干细胞体内行为的方式研究干细胞的自我更新和分化，并通过人类干细胞的定向分化来定制设计组织移植物。