There is a fundamental lack of understanding in how the structure and architecture of a synthetic polymer influences recognition in biological systems. Furthermore, there is a disconnection between the properties of polymers in solution and the solid state with their relationships with biological systems. Understanding how the conformational dynamics of a synthetic polymer can enhance biological recognition will advance fields including targeted drug delivery, antimicrobial agents, and tissue engineering. However, gaining the knowledge required to address this fundamental gap first necessitates the capability to synthesize precision macromolecules and scaffolds through a biocompatible approach. The long-term goal of this project is to establish a modular polymerization technology, using organic photocatalysts, for 3D printing of scaffolds with precisely defined molecular, chemical, mechanical, and geometric properties targeting lung tissue restoration. The central hypothesis of this research program is that the ability to use our biocompatible photo- mediated polymerization technology for 3D printing of scaffolds with defined components over several different length scales will enable tuning the scaffold for nurturing tissue growth. The overall objective of this application is to advance our polymerization technology using organic photocatalysts to mediate a metal free atom transfer radical polymerization en route to realizing a stereospecfic radical polymerization through flow chemistry reaction engineering design. With the capability to synthesize functionally diverse stereoregular polymers, we will determine the effects of polymer tacticity on their antimicrobial activity and selectivity for bacteria and compatibility with mammalian cells. Through catalyst development and expansion of monomer scope, we will establish a photographic photolithography approach to write distinct 2 and 3D polymer patterns in chemical composition through monomer selection. Furthermore, our approach to connect polymers in solution to those in the solid state will investigate molecular brush copolymers as intermediate macromolecules that possess characteristics similar to both forms. We will introduce these molecular brush copolymers into biological systems to explore the differences between them and the discrete polymer chains from our concurrent cell studies. These findings will help resolve the essential structural features of polymers to yield efficient solid state scaffolds for tissue engineering. The innovation of this research is within the methodology built upon our group?s foundational and ongoing work of developing an organocatalyzed atom transfer radical polymerization, which promises to yield new materials for introduction in biomedical applications. The rationale for this research is that it brings forth new materials that are only accessible through the development of our polymerization technology, which will allow the design and synthesis of polymers that more efficiently mimic natural systems for enhanced biological recognition.

Public Health Relevance

Organic Polymerization Catalysis: Precision Macromolecules for Recognition in Biological Systems Garret M. Miyake, University of Colorado at Boulder Department of Chemistry and Biochemistry and Materials Science and Engineering Program Project Narrative. The proposed research is relevant to public health because the establishment of new biocompatible polymerization methods ultimately increases the capability to produce designer soft materials and extend application of synthetic macromolecules into biomedical applications, including targeted drug delivery, antimicrobial agents, and tissue engineering. The research proposal will apply this new photopolymerization methodology to produce macromolecules for understanding biological recognition and enable design of advanced scaffolds for lung tissue engineering. The proposed research addresses the mission of the NIGMS for increasing the understanding in which synthetic macromolecules, with precisely defined molecular, chemical, structural, architectural and geometric constraints interact with biological system on a range of levels.

National Institute of Health (NIH)
National Institute of General Medical Sciences (NIGMS)
Unknown (R35)
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Special Emphasis Panel (ZRG1)
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Fabian, Miles
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Colorado State University-Fort Collins
Schools of Arts and Sciences
Fort Collins
United States
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Buss, Bonnie L; Miyake, Garret M (2018) Photoinduced Controlled Radical Polymerizations Performed in Flow: Methods, Products, and Opportunities. Chem Mater 30:3931-3942
Lim, Chern-Hooi; Kudisch, Max; Liu, Bin et al. (2018) C-N Cross-Coupling via Photoexcitation of Nickel-Amine Complexes. J Am Chem Soc 140:7667-7673
McCarthy, Blaine G; Pearson, Ryan M; Lim, Chern-Hooi et al. (2018) Structure-Property Relationships for Tailoring Phenoxazines as Reducing Photoredox Catalysts. J Am Chem Soc 140:5088-5101
Rao, Heng; Lim, Chern-Hooi; Bonin, Julien et al. (2018) Visible-Light-Driven Conversion of CO2 to CH4 with an Organic Sensitizer and an Iron Porphyrin Catalyst. J Am Chem Soc :
Buss, Bonnie L; Beck, Logan R; Miyake, Garret M (2018) Synthesis of Star Polymers using Organocatalyzed Atom Transfer Radical Polymerization Through a Core-first Approach. Polym Chem 9:1658-1665
Learsch, Robert; Miyake, Garret M (2018) Arm-First Synthesis of Star Polymers with Polywedge Arms Using Ring-Opening Metathesis Polymerization and Bifunctional Crosslinkers. J Polym Sci A Polym Chem 56:732-740
Sartor, Steven M; McCarthy, Blaine G; Pearson, Ryan M et al. (2018) Exploiting Charge-Transfer States for Maximizing Intersystem Crossing Yields in Organic Photoredox Catalysts. J Am Chem Soc 140:4778-4781
Rapf, Rebecca J; Perkins, Russell J; Yang, Haishen et al. (2017) Photochemical Synthesis of Oligomeric Amphiphiles from Alkyl Oxoacids in Aqueous Environments. J Am Chem Soc 139:6946-6959
Liu, Bin; Lim, Chern-Hooi; Miyake, Garret M (2017) Visible-Light-Promoted C-S Cross-Coupling via Intermolecular Charge Transfer. J Am Chem Soc 139:13616-13619
Theriot, Jordan C; McCarthy, Blaine G; Lim, Chern-Hooi et al. (2017) Organocatalyzed Atom Transfer Radical Polymerization: Perspectives on Catalyst Design and Performance. Macromol Rapid Commun 38:

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