Advances in the fabrication of biomaterials for gradient tissue engineering

Abstract

Natural tissues and organs exhibit an array of spatial gradients, from the polar-ized neural tube during embryonic development to the osteochondral interfacepresent at articulating joints. The strong structure–function relationships inthese heterogeneous tissues have sparked intensive research into the develop-ment of methods that can replicate physiological gradients in engineered tis-sues. In this Review, we consider different gradients present in natural tissuesand discuss their critical importance in functional tissue engineering. Using thisbasis, we consolidate the existing fabrication methods into four categories: addi-tive manufacturing, component redistribution, controlled phase changes, andpostmodification. We have illustrated this with recent examples, highlightedprominent trends in thefield, and outlined a set of criteria and perspectives forgradient fabrication.