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.
Highlights
Review cues provided by the native extracellular matrix (ECM).[7−9] By doing so, cellular growth, infiltration, differentiation, and signaling can be controlled in order to aid tissue development and generate a successful clinical outcome
The processing of scaffolds to recreate the physical or topological features of native tissue,[8,10] the synthesis of polymers which mimic the chemical characteristics of ECM,[11,12] and the incorporation of functional components which bind and manipulate minerals and biomolecules in vivo[13,14] can all be used to direct cell behavior
While the natural roles of deoxyribonucleic acid (DNA) and ribonucleic acid (RNA) sequences are difficult to exploit when tethered in the extracellular environment, the structural and functional capabilities of non-natural and evolved sequences are increasingly being employed in biomaterial design
Summary
This review will be split broadly into four sections: chemical-, enzymatic-, photo-, and noncovalent conjugations (Figure 1). We will briefly discuss this key preceding literature, setting the scene for a detailed discussion of the uses and limitations of biomolecule conjugation strategies for biomaterial functionalization. For more detailed discussions on the applications of the developed materials in the tissue engineering field, as well as the wider impact of particular modification strategies outside of this area, the reader will be directed to key reviews throughout. At the end of each section we provide a table summarizing the major pros and cons of each conjugation strategy, as well as details of selectivity and orthogonality to other methods (Tables 1−4)
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