Regenerative engineering has pioneered several novel biomaterials to treat critical-sized bone injuries. However, despite significant improvement in synthetic materials research, some limitations still exist. The constraints correlated with the current grafting methods signify a treatment paradigm shift to osteoinductive regenerative engineering approaches. Because of their intrinsic potential, inductive biomaterials may represent alternative approaches to treating critical bone injuries. Osteoinductive scaffolds stimulate stem cell differentiation into the osteoblastic lineage, enhancing bone regeneration. Inductive biomaterials comprise polymers, calcium phosphate ceramics, metals, and graphene family materials. This review will assess the cellular behavior toward properties of inductive materials.

The outstanding properties of graphene materials rely on an exceptional two‐dimensional honeycombed lattice. The lattice allows for electrical, thermal, and mechanical reinforcement effects when applied to the ceramic matrix. The biocompatibility of the material allows for providing multifunctional bioceramics applications. However, the potential of graphene lies in its ability to be homogenously distributed as part of a ceramic matrix. Therefore, appropriate processing techniques are important for attaining desired graphene ceramic properties applicable for regenerative biomedical purposes. This article provides an inclusive review of the current knowledge of advanced graphene‐based ceramics for bone regenerative engineering. In this review, the opportunities and challenges in utilizing graphene materials in combination with ceramics suitable for applications in load‐bearing bone defects are discussed.

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Bone grafting procedures have become increasingly common in the United States, with approximately 500,000 cases occurring each year at a societal cost exceeding $2.4 billion. Recombinant human bone morphogenetic proteins (rhBMPs) are therapeutic agents that have been widely used by orthopedic surgeons to stimulate bone tissue formation alone and when paired with biomaterials. However, significant limitations such as immunogenicity, high production cost, and ectopic bone growth from these therapies remain. Therefore, efforts have been made to discover and repurpose osteoinductive small-molecule therapeutics to promote bone regeneration. Previously, we have demonstrated that a single-dose treatment with the small-molecule forskolin for just 24 h induces osteogenic differentiation of rabbit bone marrow–derived stem cells in vitro, while mitigating adverse side effects attributed with prolonged small-molecule treatment schemes. In this study, we engineered a composite fibrin–PLGA [poly(lactide-co-glycolide)]-sintered microsphere scaffold for the localized, short-term delivery of the osteoinductive small molecule, forskolin. In vitro characterization studies showed that forskolin released out of the fibrin gel within the first 24 h and retained its bioactivity toward osteogenic differentiation of bone marrow–derived stem cells. The forskolin-loaded fibrin–PLGA scaffold was also able to guide bone formation in a 3-mo rabbit radial critical-sized defect model comparable to recombinant human bone morphogenetic protein-2 (rhBMP-2) treatment, as demonstrated through histological and mechanical evaluation, with minimal systemic off-target side effects. Together, these results demonstrate the successful application of an innovative small-molecule treatment approach within long bone critical-sized defects.