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-beta-homoserine (beta-HS) materials consist of the hydrophilic unnatural amino acid beta-homoserine. Self-assembled monolayers (SAMs) of beta-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 beta-HS hydrogels. Strikingly, the beta-HS hydrogels induce angiogenesis in implant-adjacent tissues. Molecular dynamics simulations indicated that the low FBR performance of beta-HS results from what we term dual hydrogen bonding hydration, wherein both the backbone amide groups and the sidechain hydroxyl groups of beta-HS undergo hydration.