Natural tissues and organs exhibit an array of spatial gradients, from the polarized neural tube during embryonic development to the osteochondral interface present at articulating joints. The strong structure–function relationships in these heterogeneous tissues have sparked intensive research into the development of methods that can replicate physiological gradients in engineered tissues. In this Review, we consider different gradients present in natural tissues and discuss their critical importance in functional tissue engineering. Using this basis, we consolidate the existing fabrication methods into four categories: additive manufacturing, component redistribution, controlled phase changes, and postmodification. We have illustrated this with recent examples, highlighted prominent trends in the field, and outlined a set of criteria and perspectives for gradient fabrication.

天然组织和器官表现出一系列空间梯度，从胚胎发育过程中的极化神经管到关节处的骨软骨界面。这些异质组织中强大的结构 - 功能关系引发了对开发可以在工程组织中复制生理梯度的方法的深入研究。在这篇综述中，我们考虑了天然组织中存在的不同梯度，并讨论了它们在功能性组织工程中的重要性。在此基础上，我们将现有的制造方法整合为四类：增材制造、组件重新分布、受控相变和后修改。我们用最近的例子说明了这一点，突出了该领域的突出趋势，