Covalent Peptide‐Graphene Conjugates for Enhanced Cell Spreading, Osteogenic Differentiation, and Angiogenesis in Bone Defects

Traumatic bone injury is one of the most common injuries that require surgical intervention, and current treatments suffer severe drawbacks. Modern research in bone regeneration focuses on implants that will support and enhance native tissue regeneration. One scaffold material that shows promise is graphene oxide (GO), a 2D nanomaterial made from oxidation of graphite. GO is biocompatible, strong, osteoinductive, is safely and slowly resorbed by the body, has a cheap, facile, and scalable synthesis, and is highly tailorable and functionalizable. The bioactivity of GO can be enhanced via functionalization with biomolecules such as peptides, proteins, and small molecules. Here, short peptides RGD, DGEA, and KKGHK are covalently bound to GO through a Claisen modification (CG) to create new functional graphenic materials that are cell-adhesive, osteogenic, and angiogenic, respectively. These peptide-Claisen graphenes (peptide-CGs) are found to be cytocompatible, to encourage cell spreading on the graphenic surface, to promote osteogenesis in stem cells, and to induce angiogenesis in vascular endothelial cells. They show promise as next-generation bone regeneration scaffolds by overcoming challenges frequently faced by bone regeneration scaffolds, namely retaining implanted and recruited cells, promoting their survival, proliferation, and differentiation, and ensuring a sufficient oxygen and nutrient supply to new tissue.