Biosynthetic Polymers as Functional Materials

Abstract

The synthesis of functional polymers encoded with biomolecules has been an extensive area of research for decades. As such, a diverse toolbox of polymerization techniques and bioconjugation methods has been developed. The greatest impact of this work has been in biomedicine and biotechnology, where fully synthetic and naturally derived biomolecules are used cooperatively. Despite significant improvements in biocompatible and functionally diverse polymers, our success in the field is constrained by recognized limitations in polymer architecture control, structural dynamics, and biostabilization. This Perspective discusses the current status of functional biosynthetic polymers and highlights innovative strategies reported within the past five years that have made great strides in overcoming the aforementioned barriers.

Figure 1

Various architectures of functional biosynthetic polymers via the conjugation of natural and synthetic moieties. (a) Biopolymers (polysaccharides, polynucleic acids, oligopeptides, and proteins) and their building blocks (nucleotides, monosaccharides, and amino acids) may be combined with (b) synthetic polymers (black) via a variety of polymerization methods. Representative controlled chain growth polymerization methods are depicted above uncontrolled versions. (c) The resulting functional biosynthetic polymers may act as an unstructured conjugate with various architectures or conjugate assemblies.

Figure 2

Strategy for the polymerization of unstrained macrocycles enabling primary sequence control. Monomers are composed of a ROMP polymerization trigger attached to a series of glycolate (Gly), (S)-lactate (Lact), (S)-phenyllactate (PhLact), and β-alanine (^βAla). Reproduced with permission from ref (67).

Figure 3

IEG-inspired iterative synthesis of sequence and stereocontrolled polymers. (a) Example of a 32-mer prepared by (b) orthogonal azidification, functionalization and silyl deprotection of two chiral monomers (1S, 1R) followed by CuAAC “click” of key stereoisomeric intermediates to generate polymers with precise sequences and stereochemistry. Adapted with permission from ref (88).

Figure 4

Enzyme-responsive peptide–polymer amphiphiles change shape in response to biological stimulus. (a) Diagram of a dye-labeled brush peptide–polymer amphiphile (PPA) bearing an MMP-9 specific recognition sequence, shown underlined. PPAs self-assemble into nanoparticles through hydrophobic–hydrophilic interactions when dialyzed into aqueous buffer. (b) Responsive nanoparticles aggregate in response to enzymatic cleavage by TEM. (c) Injection of particles into an infarcted heart (left) result in infarct-specific aggregation and retention over healthy tissue by fluorescence (middle and right). Scale bar: 100 μm. Adapted with permission from ref (97).

Figure 5

Self-assembled hydrogels utilizing polymer–nanoparticle (PNP) interactions. (a) Dodecyl-derivatized hydroxypropylmethylcellulose (HPMC-C₁₂) polymer and core–shell PEG-b-PLA based NPs are (b) mixed to form hydrogels where polymer chains adsorb to NPs to create transient noncovalent interactions. (c) These hydrogels shear-thin and self-heal repeatedly as shown by rheology. Adapted with permission from ref (109).

Figure 6

Mussel-inspired polycatechols as healable gels. (a) UV radical polymerization of silyl protected catechol acrylate monomer using a photoinitiator. (b) Adhesive interactions measured between semi-rigid polymer films functionalized with silyl protected catechols (catechol blocked) and deprotected catechols (catechol exposed). Dashed lines with open circles indicate delamination of the polymer from the substrate surface. (c) Scheme depicting the self-healing property of semi-rigid polycatechol acrylate rods after an initial incision, immersion in pH 3 buffer for silyl deprotection, and subsequent rejoining. Inset diagram shows hydrogen bonding interactions between deprotected catechols. Adapted with permission from ref (124).

Figure 7

Trehalose and ethoxylated polyol (EP) hydrogel components for stabilizing model proteins. (a) Thiol–ene cross-linking of diacrylate functionalized trehalose (TDA) with EP, showing hydrogen-bonding interactions between trehalose and horseradish peroxidase (HRP) within the hydrogel network. (b) Increasing trehalose content in the hydrogel correlates with greater percent recovery of active protein during release. (c) Measured stability of HRP within the trehalose gel 1, 72, or 48 h of lyophilization and subsequent rehydration for 24 h. Adapted with permission from ref (136).

Figure 8

A heparin-mimicking polymer conjugate stabilizes bFGF. (a) Conjugation of bFGF to a styrenesulfonate and poly(ethylene glycol) bearing methyl methacrylate copolymer (bFGF-p(SS-co-PEGMA)) (b) stabilizes the protein to prolonged storage, heat, acidic conditions, and enzymatic degradation. Adapted with permission from ref (159).