SGER: Laser-Layered Microfabrication of Tissue Engineering Scaffolds with Spatially Distributed Microenvironments

0313425罗伊组织工程仍然是现代生物医学研究中最令人兴奋的承诺之一。创建功能性细胞结构以增强或替换体内患病组织的概念已经探索了近十年。 从基础生物学和动物研究中获得的关于各种生长因子和支架特性对成体和胚胎干细胞的影响的知识为器官再生开辟了新的方向。然而，当前努力的基本限制之一是无法在单一支架环境内以预先设计的方式产生混合组织结构。 目前，大多数支架技术仅允许“大量”掺入生物因子，即随机分布在整个基质中的因子。复杂的空间模式沿着多个信号分子在干细胞的直接微环境中的时间分布，天然组织发育的标志尚未被工程化和研究。在这个探索性项目中，PI计划测试一种多功能的、基于激光的、逐层制造工艺的可行性，以在3D支架内创建生物因子的精确时空分布，并研究它们对干细胞分化为多个谱系的影响。 长期目标是设计混合组织结构。 为期一年的项目的目标是：1）开发计算机控制的激光分层聚合装置，以微制造复杂的、多孔的、水凝胶样支架结构和2）研究这种设置产生（a）具有限定的和空间变化的孔隙率的支架和（B）这些支架内的可溶性生物因子和聚合物微粒的空间图案化的能力。明确的物理和生物化学性质将通过提供适用于各种组织工程和器官再生问题的平台技术来推进组织工程。

0313425RoyTissue engineering remains one of the most exciting promises of modern biomedical research. The concept of creating functional cellular structures to augment or replace diseased tissue in the body has being explored for almost a decade. The knowledge gained from fundamental biological and animal research on the effects of various growth factors and scaffold properties on adult and embryonic stem cells has opened new directions in organ regeneration. However, one of the fundamental limitations of current efforts has been the inability to produce hybrid tissue structures, in a pre-designed fashion, inside a single scaffold environment. Currently, most scaffolding techniques only allow incorporation of bio-factors "in bulk", i.e. factors distributed randomly throughout the matrix. Complex spatial patterning along with temporal distribution of multiple signaling molecules in the immediate microenvironment of stem cells, a hallmark of native tissue development has yet to be engineered and studied. In this exploratory project, the PI plans to test the feasibility of a versatile, laser-based, layer-by-layer fabrication process to create precise spatio-temporal distribution of bio-factors within 3D scaffolds and study their effects on stem cell differentiation into multiple lineages. The long-term goal is to engineer hybrid tissue structures. Aims for the one-year project are: 1) Develop a computer-controlled laser-layered polymerization setup to micro-fabricate complex, porous, hydrogel-like scaffold structures and 2) Study the ability of this setup to create (a) scaffolds with defined and spatially varying porosities and (b) spatial patterning of soluble bio-factors and polymer microparticles within these scaffolds.The successful development of 3D scaffolds with pre-defined physical and biochemical properties would advance tissue engineering by providing a platform technology applicable to a diverse range of tissue engineering and organ regeneration problems.