Hybrid Living Materials: Digital Design and Fabrication of 3D Multimaterial Structures with Programmable Biohybrid Surfaces

Abstract

Significant efforts exist to develop living/non‐living composite materials—known as biohybrids—that can support and control the functionality of biological agents. To enable the production of broadly applicable biohybrid materials, new tools are required to improve replicability, scalability, and control. Here, the Hybrid Living Material (HLM) fabrication platform is presented, which integrates computational design, additive manufacturing, and synthetic biology to achieve replicable fabrication and control of biohybrids. The approach involves modification of multimaterial 3D‐printer descriptions to control the distribution of chemical signals within printed objects, and subsequent addition of hydrogel to object surfaces to immobilize engineered Escherichia coli and facilitate material‐driven chemical signaling. As a result, the platform demonstrates predictable, repeatable spatial control of protein expression across the surfaces of 3D‐printed objects. Custom‐developed orthogonal signaling resins and gene circuits enable multiplexed expression patterns. The platform also demonstrates a computational model of interaction between digitally controlled material distribution and genetic regulatory responses across 3D surfaces, providing a digital tool for HLM design and validation. Thus, the HLM approach produces biohybrid materials of wearable‐scale, self‐supporting 3D structure, and programmable biological surfaces that are replicable and customizable, thereby unlocking paths to apply industrial modeling and fabrication methods toward the design of living materials.

Three-dimensional Printing of Customized Bioresorbable Airway Stents

“…In combination with medical imaging techniques, three dimensional (3D) printing technologies [6][7][8][9][10][11][12][13] , such as digital light processing (DLP) 14 , provide enormous opportunities for rapid and affordable production of personalized medical devices [15][16][17][18][19] , including airway stents 5 . This specific manufacturing technology is based on the localized light-initiated photopolymerization of a liquid resin containing (macro)monomers 6,20 .…”

Digitally Fabricated and Naturally Augmented In Vitro Tissues

“…A new era of biohybrid customizable in vitro tissues and wearables is coming of age. [ 7 ] Computational models of interaction between a digitally controlled material distribution and biological functionality are the next frontier in biomedical research. Not only have digital fabrication platforms been used to template cells and biomaterials, they were also employed to position exogenous chemical and environmental signals.…”

“…In an inspiring study, the release of chemical signals that regulate gene expression in a 3D construct was modeled in silico and later validated with an in vitro model in a repeatable and predictable way (Figure 3G). [ 7 ] The inducing substance isopropyl β ‐D‐1‐thiogalactopyranoside (IPTG) was incorporated into acrylic‐based photopolymeric inks (rigid VeroClear (Stratasys RGD810), flexible TangoPlus (Stratasys FLX930), and hygroscopic FullCure Support (Stratasys SUP705)), printed in specific areas, and sprayed with E. coli ‐loaded agarose hydrogel. E. coli cleaved β ‐galactosidase (an enzyme occurring in E. coli ) into glucose and galactose (expressed in blue color), demonstrating the metabolic activity of these cells after printing.…”

Digital biofabrication to realize the potentials of plant roots for product design

“…Researchers have achieved to embed cells of microorganism, animal and plant origins into a variety of scaffold using digital fabrication technologies (e.g. [4,[13][14][15][16][17][18]). Today, potential applications of biodesign vary from biological energy sources (e.g.…”