Virus-like particles as modular interfaces for biomaterial functionalization

Biomaterial surface biofunctionalization refers to the process of modifying a biomaterial's surface to improve its interaction with biological systems. Controlling cell-material interactions is crucial, but current methods using native extracellular matrix (ECM) proteins, typically derived from human or animal tissue, or synthetic peptides are hampered by limitations such as batch variability, high cost, poor surface adsorption, and limited control over peptide presentation. This study introduces a technology that uses virus-like particles (VLPs) displaying biomimetic ECM-derived peptides. We engineered VLPs to present the RGD motif (arginine-glycine-aspartic acid), a well-established sequence that promotes cell adhesion, using either direct genetic fusion or SpyTag/SpyCatcher ligation, with the latter providing a more versatile conjugation strategy. These VLPs effectively functionalized cell-repellent silicone surfaces, significantly enhancing cell adhesion, migration, proliferation, and differentiation, achieving performance comparable with or exceeding that of native ECM proteins or synthetic RGD peptides. Additionally, the VLP/SpyCatcher particle enabled the co-presentation of multiple bioactive peptides, opening avenues for complex tissue engineering strategies. This tunable system represents a powerful tool for directing cell behavior, with significant potential for advancing nanomedicine and biomaterials development.