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      Achieving Controlled Biomolecule–Biomaterial Conjugation

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          Abstract

          The conjugation of biomolecules can impart materials with the bioactivity necessary to modulate specific cell behaviors. While the biological roles of particular polypeptide, oligonucleotide, and glycan structures have been extensively reviewed, along with the influence of attachment on material structure and function, the key role played by the conjugation strategy in determining activity is often overlooked. In this review, we focus on the chemistry of biomolecule conjugation and provide a comprehensive overview of the key strategies for achieving controlled biomaterial functionalization. No universal method exists to provide optimal attachment, and here we will discuss both the relative advantages and disadvantages of each technique. In doing so, we highlight the importance of carefully considering the impact and suitability of a particular technique during biomaterial design.

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          Thiol-ene click chemistry.

          Following Sharpless' visionary characterization of several idealized reactions as click reactions, the materials science and synthetic chemistry communities have pursued numerous routes toward the identification and implementation of these click reactions. Herein, we review the radical-mediated thiol-ene reaction as one such click reaction. This reaction has all the desirable features of a click reaction, being highly efficient, simple to execute with no side products and proceeding rapidly to high yield. Further, the thiol-ene reaction is most frequently photoinitiated, particularly for photopolymerizations resulting in highly uniform polymer networks, promoting unique capabilities related to spatial and temporal control of the click reaction. The reaction mechanism and its implementation in various synthetic methodologies, biofunctionalization, surface and polymer modification, and polymerization are all reviewed.
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            Photodegradable hydrogels for dynamic tuning of physical and chemical properties.

            We report a strategy to create photodegradable poly(ethylene glycol)-based hydrogels through rapid polymerization of cytocompatible macromers for remote manipulation of gel properties in situ. Postgelation control of the gel properties was demonstrated to introduce temporal changes, creation of arbitrarily shaped features, and on-demand pendant functionality release. Channels photodegraded within a hydrogel containing encapsulated cells allow cell migration. Temporal variation of the biochemical gel composition was used to influence chondrogenic differentiation of encapsulated stem cells. Photodegradable gels that allow real-time manipulation of material properties or chemistry provide dynamic environments with the scope to answer fundamental questions about material regulation of live cell function and may affect an array of applications from design of drug delivery vehicles to tissue engineering systems.
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              Tetrazine ligation: fast bioconjugation based on inverse-electron-demand Diels-Alder reactivity.

              Described is a bioorthogonal reaction that proceeds with unusually fast reaction rates without need for catalysis: the cycloaddition of s-tetrazine and trans-cyclooctene derivatives. The reactions tolerate a broad range of functionality and proceed in high yield in organic solvents, water, cell media, or cell lysate. The rate of the ligation between trans-cyclooctene and 3,6-di-(2-pyridyl)-s-tetrazine is very rapid (k2 2000 M-1 s-1). This fast reactivity enables protein modification at low concentration.
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                Author and article information

                Journal
                Chem Rev
                Chem. Rev
                cr
                chreay
                Chemical Reviews
                American Chemical Society
                0009-2665
                1520-6890
                24 July 2018
                22 August 2018
                : 118
                : 16
                : 7702-7743
                Affiliations
                []Department of Medical Biochemistry and Biophysics, Karolinska Institutet , Scheeles Väg 2, Stockholm, Sweden
                []NJ Centre for Biomaterials, Rutgers University , 145 Bevier Road, Piscataway, New Jersey United States
                [§ ]Department of Materials, Department of Bioengineering, and Institute of Biomedical Engineering, Imperial College London , Exhibition Road, London, United Kingdom
                Author notes
                Article
                10.1021/acs.chemrev.8b00253
                6107854
                30040387
                aa323273-dce6-460f-9257-7c3c80691e92
                Copyright © 2018 American Chemical Society

                This is an open access article published under a Creative Commons Attribution (CC-BY) License, which permits unrestricted use, distribution and reproduction in any medium, provided the author and source are cited.

                History
                : 19 April 2018
                Categories
                Review
                Custom metadata
                cr8b00253
                cr-2018-00253w

                Chemistry
                Chemistry

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