Biomimetic materials for tissue engineering

在胚胎发育过程中，细胞在自身周围分泌细胞外基质（ECM），进而为细胞指导器官发育提供线索。因此，同样的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ECM类似物的仿生材料，能够维持类似天然ECM的环境，并与宿主组织和干细胞相互作用以实现再生。由于不同患者的特殊需求不同，因此这些生物材料的组合方法非常可取，其中模块化元素将被整合到可定制的平台中。具体来说，我们将重点关注上皮组织，即无上皮组织和含有成纤维细胞的下层ECM组织，如角膜和皮肤。我们的患者群体将包括干细胞储备有限的老年人，因此，再生能力有限。这包括神经支配丧失导致慢性足部溃疡（糖尿病足）的糖尿病患者，以及由于神经丧失和表面溃疡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，作为组装成具有定制特定生物活性的ECM类似物的构建块，特别是用于调节干细胞活性。然后我们将它们组装成简单的3-D ECM类似物，并测试它们的光学清晰度、机械强度和生物相容性等特性。显示出理想性能的材料将进一步被设计成更复杂的角膜和皮肤结构，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 turnprovides cues to the cells to direct organ development. The same ECM componants would therefore also belikely to direct repair and regeneration of these organs. Our goal, therefore, is to develop biomimetic materialsthat are ECM analogs, capable of sustaining a native-like ECM environment and interacting with host tissuesand stem cells to effect regeneration. As particular requirements vary from patient to patient, a combinatorialapproach to these biomaterials, in which modular elements would be incorporated into a customizableplatform, would be very desirable. Specifically, we will be focus on epithelial tissues, i.e. tissues with anepithelium and underlying ECM containing fibroblastic cells such as the cornea and skin. Our patientpopulation will include elderly individuals with limited stem cell reserves and therefore, regenerationcapability. 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 forassembly 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 opticalclarity, mechanical strength and biocompatobility. Materials that show desirable properties will then be furtherengineered into more complex cornea and then skin constructs, after which we will test their ability to controlcell behavior. Our aim is to control stem cell behavior in these engineered tissues and well as in-growth ofnerve and blood vessels into these constructs.