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

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.