Silk‐Inspired β‐Peptide Materials Resist Fouling and the Foreign‐Body Response

Abstract The functions of implants like medical devices are often compromised by the host's foreign‐body response (FBR). Herein, we report the development of low‐FBR materials inspired by serine‐rich sericin from silk. Poly‐β‐homoserine (β‐HS) materials consist of the hydrophilic unnatural amino acid β‐homoserine. Self‐assembled monolayers (SAMs) of β‐HS resist adsorption by diverse proteins, as well as adhesion by cells, platelets, and diverse microbes. Experiments lasting up to 3 months revealed that, while implantation with control PEG hydrogels induced obvious inflammatory responses, collagen encapsulation, and macrophage accumulation, these responses were minimal with β‐HS hydrogels. Strikingly, the β‐HS hydrogels induce angiogenesis in implant‐adjacent tissues. Molecular dynamics simulations indicated that the low FBR performance of β‐HS results from what we term “dual hydrogen bonding hydration”, wherein both the backbone amide groups and the sidechain hydroxyl groups of β‐HS undergo hydration.