This review provides a comprehensive overview of the latest advances in the synthesis, architectural design and biomedical applications of polypeptides and their hybrids.

The high toughness of natural spider-silk is attributed to their unique β-sheet secondary structures. However, the preparation of mechanically strong β-sheet rich materials remains a significant challenge due to challenges involved in processing the polymers/proteins, and managing the assembly of the hydrophobic residues. Inspired by spider-silk, our approach effectively utilizes the superior mechanical toughness and stability afforded by localised βsheet domains within an amorphous network. Using a grafting-from polymerisation approach within an amorphous hydrophilic network allows for spatially controlled growth of poly (valine) and poly(valine-r-glycine) as β-sheet forming polypeptides via N-carboxyanhydride ring opening polymerisation. The resulting continuous β-sheet nanocrystal network exhibits improved compressive strength and stiffness over the initial network lacking β-sheets of up to 30 MPa (300 times greater than the initial network) and 6 MPa (100 times greater than the initial network) respectively. The network demonstrates improved resistance to strong acid, base and protein denaturants over 28 days.

Synthetic polypeptide-based macroporous cryogels with inherent antimicrobial properties were prepared for potential water purification applications. Gels were chemically cross-linked through the amine residue of a polycationic polylysine-b-polyvaline block copolymer with glutaraldehyde as cross-linker under cryogenic conditions. These cryogels exhibited excellent water swelling and highly compressible mechanical properties owing to their macroporous structure. The antibacterial performance was evaluated based on E. coli viability, with cryogels exhibiting up to 95.6% reduction in viable E. coli after a brief 1 h incubation. In comparison to the hydrogel control, the presence of macropores is shown to be vital to the antimicrobial effect of the gels. The confined environment and increased antimicrobial surface area of the macropores is believed to result in a "trap and kill" mechanism. Mechanical strength and pore integrity of cryogels were also found to be determinants for antibacterial activity. Along with the lack of toxic leaching, these cryogels with inherent antimicrobial properties pose as potential candidates for use in biological and environmentally friendly water purification applications.

Synthetic polypeptides are a class of bioinspired polymers with well demonstrated biocompatibility, enzyme biodegradability, and cell adhesive properties, making them promising materials for the preparation of macroporous hydrogels as 3D cellular scaffolds. Three-dimensional macroporous hydrogels composed entirely of biocompatible and enzyme biodegradable synthetic polypeptides have thus been prepared. Under cryoconditions, macroporous hydrogels in the form of macroporous cryogels were prepared using a single copolymer component through direct EDC/sulfo-NHS zero-length cross-linking between poly(l-glutamic acid) (PLG) and poly(l-lysine) (PLL) residues on a PLG-r-PLL random copolypeptide chain. The resulting macroporous cryogels were found to contain large interconnected pores (≥100 μm) highly suitable for tissue engineering applications. Tuning the relative ratios of the amino acid components could result in cryogels with very different pore structures, swelling, and mechanical properties, suitable for developing gels for a range of possible soft tissue engineering applications. These cryogels were shown to be enzymatically biodegradable and demonstrated excellent biocompatibility, cell attachment and cell proliferation profiles with mammalian fibroblast (NIH-3T3) cells, demonstrating the appeal of these novel cryogels as highly suitable cellular scaffolds.

No abstract