Bio-Inspired Morphogenesis Using Microvascular Networks and Reaction-Diffusion Maya Kleiman, † Kyle S. Brubaker, † Du T. Nguyen, ‡ and Aaron P. Esser-Kahn* ,† † Department of Chemistry, University of California, Irvine, California 92697, United States ‡ Department of Physics and Astronomy, University of California, Irvine, California 92697, United States * S Supporting Information ABSTRACT: Microstructure is a critical element of many synthetic materials including materials for separations, heat transfer, and electrical energy storage. Similarly, natural systems employ micro- structure for most structural and mass transfer processes. These systems achieve high-levels of performance through continuous, structural remodeling, which enables adaptation and improvement of their raw materials. In contrast, current microfabrication techniques produce static materials that do not adapt. Here, we show a fabrication process inspired by biological systems capable of adaptation. Combining the basic elements of morphogenesis, reaction and diffusion (RD), and a microvascular scaffold, we pattern microstructured materials by balancing the rates of depolymerization and inhibition of that depolymerization with a diffusive agent. As a result, the materials continuously reshape their microstructure and improve their performance. Using this system, we also recapitulate a hallmark of biological structures, formation of asymmetry from symmetric precursors. By mimicking nature’s processes rather than its structure, we present a method for microfabrication that improves material performance in response to a selective pressure. ■ INTRODUCTION Material microstructure is a key design element in advanced materials. Microstructure improves a material’s performance for compression, mass and heat transfer, and solar energy conversion efficiency. 1-8 Shaping microstructures is also important in biological composites. Natural composites gain unmatched performance by continuously adapting their microstructure to their environment via reaction-diffusion (RD) sequences, a process termed morphogenesis. 9-14 RD is the formation of spatial micropatterns by two reactive molecules diffusing at distinct, controlled rates. 15 During lung development, for example, microstructures are morphed via RD. This action increases the efficiency of gas exchange by changing a micron-scale bud to a half-meter-long, hierarchical composite composed of thousands of identical micron-scale alveoli 16-22 (Figure 1A and B). Current RD-based synthesis of microstructures create elegant patterns 23-27 from microns to millimeters, 25,28-30 but they are not a continuous process, are incapable of adaptation, and are limited to two dimensions. Still lacking in synthetic systems is the dynamic, continuous restructuring of 3D patterns that are the key principle that biological systems use to improve performance. Here, we show a synthetic system that improves micro- structure performance through RD-based microstructure change. Inspired by lung morphogenesis, we developed a synthetic depolymerization/inhibition (push/pull) method that remodels microstructures dynamically. Our method selectively improved the mass transfer performance of an experimental microcontactor and allowed us to fabricate asymmetric structures from symmetric precursors. We developed a finite element model using COMSOL to describe the function and results of the process. Microstructures dictate the properties of bulk materials as diverse as composites and batteries and optimization of these structures is an active area of research. 31-33 Adaptive RD-based micro fabrication could be used for dynamically altering such structures to adapt a material to a given function. In our previous work, we fabricated 3D microstructured materials using VaSC (vaporization of a sacrificial component) and formed patterns of 3-dimensional circular channels. 34,35 (Experimental Section and Supporting Information) In the current work, we use diffusion between the channels, formed by VaSC, as the basis for our RD-based restructuring method. (Figure 1) To continuously change the shape of our template microvascular structure, we sought a reaction scheme that enabled dynamic, continuous remodeling. We developed a synthetic RD push/pull mechanism inspired by lung restructur- ing (Figure 1B and C). In the system, a circular channel is changed by a depolymerizing agent as the first, push, component (arrows). To counter depolymerization, a sacrifi- cial, reactive agent in an adjacent channel diffuses through the material. This reactive agent inhibits depolymerization, creating the second, pull component (T-junction). The rate of structural Received: May 23, 2015 Revised: June 19, 2015 Published: June 22, 2015 Article pubs.acs.org/cm © 2015 American Chemical Society 4871 DOI: 10.1021/acs.chemmater.5b01947 Chem. Mater. 2015, 27, 4871-4876