3-D BIOMIMETIC SCAFFOLDS FOR BONE TISSUE ENGINEERING

用于骨组织工程的 3D 仿生支架

• 批准号: 6634668
• 负责人: DAVID H. KOHN
• 金额: $ 21.06万
• 依托单位: UNIVERSITY OF MICHIGAN AT ANN ARBOR
• 依托单位国家: 美国
• 财政年份: 2001
• 资助国家: 美国
• 起止时间: 2001-04-01 至 2006-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6634668
• 关键词: acidity /alkalinity; apatites; biomaterial development /preparation; biomimetics; biotechnology; biotransformation; bone; bone marrow; bone regeneration; cell differentiation; cell proliferation; composite resins; copolymer; dental materials; extracellular matrix; gene expression; human tissue; laboratory mouse; normal ossification; osteoblasts; polymers; protein biosynthesis; tissue /cell culture; tissue engineering; tissue support frame

DESCRIPTION (Adapted from the Investigator's Abstract): Reconstruction of skeletal defects represents a major clinical challenge with over 1 million surgical procedures performed each year. New strategies of regenerating bone are needed because of limitations with existing techniques. One new strategy is to create a composite graft in which autologous cells are seeded onto a porous, degradable scaffold. The scaffold supports the cells, structurally and biologically, allowing them to grow and secrete new extracellular matrix. Optimally tissue growth occurs concurrent with scaffold degradation. The degree of new bone formation is, however, material dependent and not predictable. We therefore seek to establish material chemistry parameters that could optimize bone cell function. In pursuit of this goal, we have developed: (1) in vitro culture methods in which human bone marrow stromal cells (BMSCs) are expanded; (2) polymer processing techniques to reproducibly fabricate highly porous 3D poly(lactic-co-glycolic) scaffolds, which have been successfully used to engineer a number of tissues including bone; (3) materials science design strategies which enable us to biomimetically modify both the internal microenvironment of a scaffold and the scaffold surface; and (4) a critical size cranial defect model in an immunocompromised mouse which has shown that the human BMSCs are capable of forming new bone in an animal model. The global hypothesis of the proposed research is that the extracellular microenvironment provided by the scaffold modulates the ability of human BMSCs to differentiate toward an osteoblast phenotype, and therefore controls biomineralization and structural integrity of regenerated bone. Results from our and other laboratories support this hypothesis, which is tested by synthesizing a series of model biomimetic materials. First, we synthesize environmentally responsive or "smart" scaffolds that buffer the microenvironment upon scaffold degradation. Second, we synthesize scaffolds with a surface that self-mineralizes into a biological apatite. Third, we use functionally-graded scaffolds in which mineralization is spatially controlled. The rationale for each of these 3 biomimetic strategies lies in the way nature has designed the skeleton. The skeletal system is able to perform its functions using a minimum amount of mass because biology has utilized design approaches, which include the ability to adapt to environmental cues (i.e. "smartness"), a hierarchical organization consisting of elegant mineral synthesis, and an organization that is optimized for physiological function by having gradients in composition and structure. In the proposed studies, we aim to exploit aspects of each of these 3 biomimetic strategies in an effort to create biomaterials that will modulate biological response in a controlled manner.

描述（改编自调查员的摘要）：重建 骨骼缺陷代表了一个主要的临床挑战，超过100万 每年进行手术程序。再生骨的新策略 由于现有技术的局限性而需要。一个新策略是 为了创建一个复合移植物，将自体细胞接种到多孔上， 可降解的脚手架。脚手架在结构和 从生物学上讲，使它们能够生长并分泌新的细胞外基质。 最佳组织生长与支架降解同时发生。学位 但是，新的骨形成是材料依赖性的，不可预测。我们 因此寻求建立可以优化的材料化学参数 骨细胞功能。为了实现这一目标，我们已经开发了：（1）体外 人骨髓基质细胞（BMSC）扩展的培养方法； （2）聚合物加工技术可重复地制造高度多孔3D 聚（乳酸 - 糖）支架，已成功用于 设计包括骨头在内的许多组织； （3）材料科学设计 使我们能够生物图修改内部的策略 脚手架和脚手架表面的微环境； （4）关键 免疫功能低下的小鼠中的大小颅骨缺陷模型，这表明 人BMSC能够在动物模型中形成新骨。全球 拟议研究的假设是细胞外微环境 由脚手架提供 迈向成骨细胞表型，因此控制生物矿化和 再生骨的结构完整性。我们和其他 实验室支持这一假设，该假设通过合成一系列的测试 模型仿生材料。首先，我们合成环境响应迅速 或“智能”脚手架，可以在脚手架上缓冲微环境 降解。其次，我们用表面合成脚手架 自矿物化为生物磷灰石。第三，我们使用功能毕业 在空间控制矿化的脚手架。理由 这三种仿生策略中的每一个都在于自然设计的方式 骨骼。骨骼系统能够使用最低执行其功能 质量量是因为生物学使用了设计方法，其中包括 适应环境提示的能力（即“智能”），一个等级制度 由优雅的矿物合成组成的组织和一个组织 通过在组成中具有梯度和 结构。在拟议的研究中，我们旨在利用这些方面的各个方面 3种仿生策略，以创建会调节的生物材料 以受控方式生物反应。