Biomedical applications of chemically-modified silk fibroin

Abstract

Silk proteins belong to a class of unique, high molecular weight, block copolymer-like proteins that have found widespread use in biomaterials and regenerative medicine. The useful features of these proteins, including self-assembly, robust mechanical properties, biocompatibility and biodegradability can be enhanced through a variety of chemical modifications. These modifications provide chemical handles for the attachment of growth factors, cell binding domains and other polymers to silk, expanding the range of cell and tissue engineering applications attainable. This review focuses on the chemical reactions that have been used to modify the amino acids in silk proteins, and describes their utility in biomedical applications.

Fig. 1

Silk is primarily composed of (Gly-Ala-Gly-Ala-Gly-Ser)₆ amino acid repeat units that self-assemble into an anti-parallel β-sheet structure.

Fig. 2

a) Amino acid composition of the heavy chain of silk fibroin (accession number P05790). Reactive amino acids present in less than 0.5% are highlighted in light gray, while reactive amino acids present in more than 0.5% are highlighted in dark gray. b) Chemical structures of the most abundant reactive amino acids in silk fibroin.

Scheme 1

Cyanuric chloride-activated coupling

Scheme 2

Carbodiimide coupling

Scheme 3

Arginine Masking

Scheme 4

Reaction with chlorosulfonic acid

Scheme 5

Diazonium coupling

Scheme 6

Tyrosinase-catalyzed grafting

Scheme 7

Poly(methacrylate) grafting