Biomimetic materials for tissue engineering

在胚胎发育过程中，细胞分泌一种细胞外基质（ECM），这反过来又为细胞提供了指导器官发育的线索。因此，相同的ECM成分也可能指导这些器官的修复和再生。因此，我们的目标是开发仿生材料，即ECM类似物，能够维持天然ECM环境，并与宿主组织和干细胞相互作用以实现再生。由于具体要求因患者而异，因此非常需要这些生物材料的组合方法，其中模块化元件将被并入可定制的平台中。具体而言，我们将关注上皮组织，即具有上皮和含有成纤维细胞的下层ECM的组织，例如角膜和皮肤。我们的患者人群将包括干细胞储备有限的老年人，因此，再生能力有限。这些包括导致慢性足部溃疡（糖尿病足）的神经支配丧失的糖尿病患者和由于神经丧失和表面溃疡而导致角膜失明的患者。因此，我们的研究计划是开发一系列人工蛋白质和糖链作为组装成ECM类似物的构建模块，这些ECM类似物具有定制的特定生物活性，特别是用于调节干细胞活性。然后，我们将这些组装成简单的3-D ECM类似物，并测试它们的光学透明度，机械强度和生物相容性等特性。然后，显示出理想特性的材料将被进一步设计成更复杂的角膜，然后是皮肤结构，之后我们将测试它们控制细胞行为的能力。我们的目标是控制干细胞在这些工程组织中的行为，以及神经和血管在这些结构中的生长。

During embryonic development, cells secrete an extracellular matrix (ECM) around themselves that is turn provides cues to the cells to direct organ development. The same ECM componants would therefore also be likely to direct repair and regeneration of these organs. Our goal, therefore, is to develop biomimetic materials that are ECM analogs, capable of sustaining a native-like ECM environment and interacting with host tissues and stem cells to effect regeneration. As particular requirements vary from patient to patient, a combinatorial approach to these biomaterials, in which modular elements would be incorporated into a customizable platform, would be very desirable. Specifically, we will be focus on epithelial tissues, i.e. tissues with an epithelium and underlying ECM containing fibroblastic cells such as the cornea and skin. Our patient population will include elderly individuals with limited stem cell reserves and therefore, regeneration capability. These include diabetic patients with loss of innervation that have resulted in chronic foot ulcerations (diabetic foot) and patients with corneal blindness due to nerve loss and surface ulcerations. Our research plan therefore is to develop  a series of artificial proteins and sugar chains as building blocks for assembly into ECM analogs with tailored specific bioactivities, specifically for modulating stem cell activity. We would then assemble these into simple 3-D ECM analogs and will test them for properties such as optical clarity, mechanical strength and biocompatobility. Materials that show desirable properties will then be further engineered into more complex cornea and then skin constructs, after which we will test their ability to control cell behavior. Our aim is to control stem cell behavior in these engineered tissues and well as in-growth of nerve and blood vessels into these constructs.