Engineering Complex, Spatially-patterned Tissue Structures from Stem Cells

利用干细胞工程设计复杂的空间图案组织结构

• 批准号: 1417134
• 负责人: Krishnendu Roy
• 金额: $ 35.12万
• 依托单位: Georgia Tech Research Corporation
• 依托单位国家: 美国
• 项目类别: Standard Grant
• 财政年份: 2013
• 资助国家: 美国
• 起止时间: 2013-07-31 至 2016-12-31
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=1417134&HistoricalAwards=false
• 关键词: Engineering; Complex; Spatially; patterned; Tissue

Roy/ 1159326 In the past decade significant advances have been made in stem cell differentiation to create engineered tissues. However, most efforts to date have focused on regenerating a homogenous tissue structure whose bulk properties are similar to that of native tissues. But, most human tissues are complex, both structurally and functionally, and possess spatially-varying compositions and mechanical properties. Directing stem cells into such mature, three-dimensionally organized, complex tissues has not yet been achieved. A model example is articular cartilage, which has been widely studied in tissue engineering for several decades. Anatomically and functionally, articular cartilage consists of four, spatially distinct regions; the superficial, transitional, deep, and calcified zones. Each zone is characterized by unique extra-cellular matrix compositions, mechanical properties and cellular organization. Classical tissue engineering approaches for creating homogenous tissue replacements for articular cartilage has failed to achieve widespread clinical effectiveness because the engineered bulk properties do not mimic native tissue function. Based on recent findings that unique material compositions can be used to direct stem cells into specific types of chondrocytes that correspond to those from the various zones of articular cartilage, this project will explore a unique multi-layered hydrogel constructs with spatially varying biomaterial-niches for simultaneously differentiating a single stem cell population into a complex articular cartilage. The knowledge gathered would provide new insights on the feasibility of engineering complex, functionally-relevant tissues whose mechanical properties and composition can vary spatially.

在过去的十年中，在干细胞分化以产生工程化组织方面已经取得了重大进展。然而，迄今为止的大多数努力都集中在再生同质组织结构，其整体性质类似于天然组织。但是，大多数人体组织在结构和功能上都很复杂，并且具有空间变化的成分和机械性能。将干细胞导入如此成熟的、三维结构的复杂组织还没有实现。一个典型的例子是关节软骨，它已经在组织工程中被广泛研究了几十年。在解剖学和功能上，关节软骨由四个空间上不同的区域组成：浅表区、过渡区、深部区和钙化区。每个区域的特征在于独特的细胞外基质成分、机械性能和细胞组织。用于产生关节软骨的同质组织替代物的经典组织工程方法未能实现广泛的临床有效性，因为工程化的整体性质不能模拟天然组织功能。基于最近的研究结果，即独特的材料组合物可用于将干细胞定向为特定类型的软骨细胞，这些软骨细胞对应于来自关节软骨的各个区域的软骨细胞，该项目将探索具有空间变化的生物材料小生境的独特多层水凝胶结构，用于同时将单个干细胞群体分化为复杂的关节软骨。所收集的知识将为工程复杂的功能相关组织的可行性提供新的见解，这些组织的机械性能和组成可以在空间上变化。