Bone fractures are the most frequent large organ, traumatic injury in humans, and some known as critical size bone defects are too large to heal on their own, requiring intervention. Traditional treatments involve bone grafts to fill the gap and metal implants for fixation, but these face many limitations. Autografts from the patient's own body require an additional surgery, increasing infection risk and creating a new injury, and can suffer from donor and graft site tissue morbidity. Allografts from another human can additionally lead to immune rejection. Metal implants are a poor mechanical match to bone, leading to stress shielding and increased risk of severe injury, and can also cause local and systemic toxicity from leaching of metal ions over time. Current research in bone regeneration favors the development of biocompatible, biodegradable scaffolds. The ideal scaffold should be mechanically similar to bone, nontoxic, cell-instructive, porous to allow for cell infiltration, and should slowly degrade over time to make room for native bone ingrowth. Graphene oxide (GO) is a promising scaffold material as it is easily and economically synthesized, strong, cytocompatible, osteoinductive, osteoconductive, has a well-characterized aqueous degradation pathway, and has tailorable porosity. It is also an ideal substrate for functionalization with biomolecules that can aid in the bone regeneration process. Covalent functionalization in particular offers sustained and tailorable bioactivity. The present work discusses novel methods of covalent functionalization of GO with peptides to (1) enhance stem cell recruitment, adhesion, and differentiation into bone (osteogenesis) and (2) encourage new blood vessel formation (angiogenesis), which is an important step in new bone growth that facilitates nutrient delivery to cells, increasing survival and proliferation. Short, side chain-protected peptides are attached to GO via nucleophilic attack by their N-terminal amine at an acyl chloride graphene (ACG) intermediate, followed by deprotection. A longer, cysteine-terminated peptide is attached via carbodiimide coupling of a maleimide linker to GO followed by a Thiol-Michael addition to attach the peptide to the linker, with both steps featuring completely aqueous chemistry. These peptide-graphene oxide conjugates are developed for the goal of concurrent use in fabricating an osteogenic and angiogenic GO-based scaffold for bone regeneration.

Cell-instructive peptide-graphene oxide conjugates for improved bone regrowth and vascularization

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ACS Fall 2022

The official archive and repository for all ACS Meetings & Expositions abstracts and select posters or presentations.