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

RoyTIssue工程仍然是现代生物医学研究中最令人兴奋的承诺之一。创造功能性细胞结构以增强或取代体内病变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影响的知识，为器官再生开辟了新的方向。然而，当前努力的根本限制之一是无法在单一支架环境中以预先设计的方式产生杂交组织结构。目前，大多数支架技术只允许“批量”地结合生物因子，即随机分布在整个基质中的因子。复杂的空间模式以及干细胞直接微环境中多个信号分子的时间分布，是天然组织发育的一个标志，尚未被工程和研究。在这个探索性项目中，PI计划测试一种通用的、基于激光的、逐层制造工艺的可行性，以在3D支架内创建生物因素的精确时空分布，并研究它们对干细胞分化为多个谱系的影响。长期目标是设计杂交组织结构。这个为期一年的项目的目标是：1)开发一种计算机控制的激光分层聚合装置，以微制造复杂的、多孔的、水凝胶状的支架结构；2)研究该装置的能力，以创建(A)具有定义的和空间变化的孔隙率的支架，以及(B)在这些支架内可溶生物因子和聚合物微粒的空间图案。具有预先定义的物理和生化特性的3D支架的成功开发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促进组织工程。

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.