title: Regulating synthetic gene networks in 3D materials.
abstract: Combining synthetic biology and materials science will enable more advanced studies of cellular regulatory processes, in addition to facilitating therapeutic applications of engineered gene networks. One approach is to couple genetic inducers into biomaterials, thereby generating 3D microenvironments that are capable of controlling intrinsic and extrinsic cellular events. Here, we have engineered biomaterials to present the genetic inducer, IPTG, with different modes of activating genetic circuits in vitro and in vivo. Gene circuits were activated in materials with IPTG embedded within the scaffold walls or chemically linked to the matrix. In addition, systemic applications of IPTG were used to induce genetic circuits in cells encapsulated into materials and implanted in vivo. The flexibility of modifying biomaterials with genetic inducers allows for patterned placement of these inducers that can be used to generate distinct patterns of gene expression. Together, these genetically interactive materials can be used to characterize genetic circuits in environments that more closely mimic cells' natural 3D settings, to better explore complex cell-matrix and cell-cell interactions, and to facilitate therapeutic applications of synthetic biology.
authors.affiliation: Translational Tissue Engineering Center, Wilmer Eye Institute and Department of Biomedical Engineering, Johns Hopkins University, Baltimore, MD 21231, USA.
authors.forename: Tara L
authors.initials: TL
authors.lastname: Deans
authors.forename: Anirudha
authors.initials: A
authors.lastname: Singh
authors.forename: Matthew
authors.initials: M
authors.lastname: Gibson
authors.forename: Jennifer H
authors.initials: JH
authors.lastname: Elisseeff
mesh_terms: D000818:Animals; D001672:Biocompatible Materials / Q000737:chemistry*; D016466:CHO Cells; D006224:Cricetinae; D004058:Diffusion; D004305:Dose-Response Relationship, Drug; D053263:Gene Regulatory Networks; D005813:Genes, Synthetic; D020100:Hydrogels / Q000737:chemistry; D007544:Isopropyl Thiogalactoside / Q000737:chemistry; D019344:Lactic Acid / Q000737:chemistry; D008297:Male; D008422:Materials Testing; D051379:Mice; D008819:Mice, Nude; D011100:Polyglycolic Acid / Q000737:chemistry; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D015398:Signal Transduction; D058615:Synthetic Biology
chemical_list: D001672:Biocompatible Materials; D020100:Hydrogels; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011100:Polyglycolic Acid; D019344:Lactic Acid; D007544:Isopropyl Thiogalactoside