Nearly six million Americans every year are affected by traumatic bone injuries. The current gold standard for treatment, bone autografts, requires surgically transferring bone from a donor site to the treatment site within the same patient. This requires two surgical sites, increasing the risk of infection as well as causing damage to the donor site. Additionally, metal implants used to provide structural support to autografts, such as screws and plates, have several drawbacks: local and systemic toxicity due to the release of metal ions, failure at the bone-metal interface, and mechanical mismatch of the bone and screw causing stress shielding of the neighboring bone, potentially leading to osteoporosis. Graphene oxide (GO) has been recently considered for use in bone implants for two main reasons, 1) the mechanical strength exceeds current standards for bone implant structural stability, and 2) GO holds inherent osteoinductivity. These properties can be used in conjunction with bioactive proteins, which are powerful in bone regeneration and unparalleled in stem cell differentiation. We present a gentle method to attach clinically relevant proteins to graphene oxide via a Mitsunobu reaction. The hydrolytically active ester bond enables controlled release of proteins from GO <i>in situ</i>. Successful covalent attachment of bovine serum albumin (BSA) was achieved to yield BSA-Mitsunobu graphene (BSA-MG), and controlled release of BSA was demonstrated over four weeks at targeted concentrations. The BSA released from MG was characterized to show a retention in secondary structure. This method may be used as an analogue for a protein-based osteoinductive agent such as bone morphogenetic protein 2 (BMP-2), enabling controlled release of protein-based therapeutics.

Gentle attachment of bioactive proteins onto graphene oxide through the Mitsunobu reaction

Macromolecular Chemistry: The Second Century

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ACS Spring 2020 National Meeting & Expo

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